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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 28 (2000), S. 14-25 
    ISSN: 1573-9686
    Keywords: Coronary anatomy ; Finite element ; Network generation ; Mathematical model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract A discrete anatomically accurate finite element model of the largest six generations of the coronary arterial network is developed. Using a previously developed anatomically accurate model of ventricular geometry the boundaries of the coronary mesh are defined from measured epicardial coronaries. Network topology is then generated stochastically from published anatomical data. Spatial information is added to this topological data using an avoidance algorithm accounting for global network geometry and optimal local branch angle properties. The generated vessel lengths, radii and connectivity are consistent with the published studies and a relativity even spatial distribution of vessels within the ventricular mesh is achieved. The local finite element coordinates of the coronary nodes within the ventricular mesh are calculated such that the coronary geometry can be recalculated within a deformed ventricular mesh. © 2000 Biomedical Engineering Society. PAC00: 8710+e, 8718Bb, 0270Dh
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  • 2
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    Electronic Resource
    Springer
    Annals of biomedical engineering 28 (2000), S. 278-290 
    ISSN: 1573-9686
    Keywords: Dehydration ; Mathematical model ; Thermoregulation ; Cardiovascular ; Respiratory ; Body water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract A model of the human body that integrates the variables involved in temperature regulation and blood gas transport within the cardiovascular and respiratory systems is presented here. It expands upon previous work to describe the competition between skin and muscles when both require increased blood flows during exercise and/or heat stress. First, a detailed study of the control relations used to predict skin blood flow was undertaken. Four other control relations employed in the model were also examined and modified as indicated by empirical results found in literature. Internal responses to exercise and/or heat stress can affect both thermoregulation and the cardiorespiratory system. Dehydration was studied in addition to complete water replacement during similar environmental and exercise situations. Control relations for skin blood flow and evaporative heat loss were modified and a water balance was added to study how the loss of water through sweat can be limiting. Runoff from sweating as a function of relative humidity was introduced along with evaporation, and these results were compared to data to validate the model. © 2000 Biomedical Engineering Society. PAC00: 8719Pp, 8719Uv, 8719Ff, 8710+e
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  • 3
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    Electronic Resource
    Springer
    Annals of biomedical engineering 28 (2000), S. 495-511 
    ISSN: 1573-9686
    Keywords: Heart ; Epicardial and endocardial differences ; Vascular growth model ; Mathematical model ; Computer simulation ; Constrained constructive optimization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract There is a marked difference in the structure of the arterial tree between epi- and endocardial layers of the human heart. To model these structural variations, we developed an extension to the computational method of constrained constructive optimization (CCO). Within the framework of CCO, a model tree is represented as a dichotomously branching network of straight cylindrical tubes, with flow conditions governed by Poiseuille's law. The tree is grown by successively adding new terminal segments from randomly selected points within the perfusion volume while optimizing the geometric location and topological site of each new connection with respect to minimum intravascular volume. The proposed method of “staged growth” guides the generation of new terminal sites by means of an additional time-dependent boundary condition, thereby inducing a sequence of domains of vascular growth within the given perfusion volume. Model trees generated in this way are very similar to reality in their visual appearance and predict diameter ratios of parent and daughter segments, the distribution of symmetry, the transmural distribution of flow, the volume of large arteries, as well as the ratio of small arterial volume in subendocardial and subepicardial layers in good agreement with experimental data. From this study we conclude that the method of CCO combined with staged growth reproduces many characteristics of the different arterial branching patterns in the subendocardium and the subepicardium, which could not be obtained by applying the principle of minimum volume alone. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8719Hh, 4760+i
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  • 4
    ISSN: 1573-9686
    Keywords: Mathematical model ; Receptor ; Renin ; Kinetic analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Numerous studies have demonstrated changes in receptor number, protein concentration, or mRNA levels and have proposed that these subcellular changes produce physiologic effects. To date, no adequate mathematical analysis has been available to provide a framework for interpretation of such data. In the present study we have combined measurements of angiotensin receptor protein levels with the development of a mathematical model that includes two receptors with opposing actions for a single ligand. This model was used to quantify the net, physiologic response of each receptor population to ANG II stimulation and the effect of altering the expression of receptor populations by a physiologic stimulus. Altered sodium intake was used as the physiologic stimulus and quantification of Western blot analysis and revealed that high sodium diet significantly suppressed AT1 receptor protein in the adrenal gland and aorta and augmented AT2 receptor protein in the aorta. A high sodium diet did not significantly alter AT2 receptor protein in the adrenal gland. Modeling the measured sodium-induced changes in receptor concentration demonstrated that small, subcellular changes in receptor concentration can have a large impact on the net physiologic effect. This model for dual receptor–single ligand interactions should be amenable for other systems. © 2000 Biomedical Engineering Society. PAC00: 8710+e, 8714Ee
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  • 5
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    Springer
    Annals of biomedical engineering 27 (1999), S. 208-218 
    ISSN: 1573-9686
    Keywords: Single cell model ; Multidrug resistance ; Cancer cell ; Drug influx and efflux ; Mathematical model ; Dynamic and steady-state simulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Multidrug resistance (MDR) of some cancer cells is a major challenge for chemotherapy of systemic cancers to overcome. To experimentally uncover the cellular mechanisms leading to MDR, it is necessary to quantitatively assess both drug influx into, and efflux from, the cells exposed to drug treatment. By using a novel molecular microdelivery system to enforce continuous and adjustable drug influx into single cells by controlled diffusion through a gel plug in a micropipet tip, drug resistance studies can now be performed on the single cell level. Our dynamic model of this scheme incorporates drug delivery, diffusive mixing, and accumulation inside the cytoplasm, and efflux by both passive and active membrane transport. Model simulations using available experimental information on these processes can assist in the design of MDR related experiments on single cancer cells which are expected to lead to a quantitative evaluation of mechanisms. Simulations indicate that drug resistance of a cancer cell can be quantified better by its dynamic response than by steady-state analysis. © 1999 Biomedical Engineering Society. PAC99: 8717Aa, 8719Xx
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  • 6
    ISSN: 1573-9686
    Keywords: Thrombosis ; Mathematical model ; Thrombin ; Fluid dynamics ; Mass transport ; Platelets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract To better understand the mechanisms leading to the formation and growth of mural thrombi on biomaterials, we have developed a two-dimensional computational model of platelet deposition and activation in flowing blood. The basic formulation is derived from prior work by others, with additional levels of complexity added where appropriate. It is comprised of a series of convection-diffusion-reaction equations which simulate platelet-surface and platelet-platelet adhesion, platelet activation by a weighted linear combination of agonist concentrations, agonist release and synthesis by activated platelets, platelet-phospholipid-dependent thrombin generation, and thrombin inhibition by heparin. The model requires estimation of four parameters to fit it to experimental data: shear-dependent platelet diffusivity and resting and activated platelet-surface and platelet-platelet reaction rate constants. The model is formulated to simulate a wide range of biomaterials and complex flows. In this article we present the basic model and its properties; in Part II (Sorensen et al., Ann. Biomed. Eng. 27:449–458, 1999) we apply the model to experimental results for platelet deposition onto collagen. © 1999 Biomedical Engineering Society. PAC99: 8719Uv, 8380Lz, 8717Aa, 8710+e, 8768+z
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  • 7
    ISSN: 1573-9686
    Keywords: Thrombosis ; Mathematical model ; Thrombin ; Fluid dynamics ; Mass transport ; Platelets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract We have previously described the development of a two-dimensional computational model of platelet deposition onto biomaterials from flowing blood (Sorensen et al., Ann. Biomed. Eng. 27:436–448, 1999). The model requires estimation of four parameters to fit it to experimental data: shear-dependent platelet diffusivity and three platelet-deposition-related reaction rate constants. These parameters are estimated for platelet deposition onto a collagen substrate for simple parallel-plate flow of whole blood in both the presence and absence of thrombin. One set of experimental results is used as a benchmark for model-fitting purposes. The “trained” model is then validated by applying it to additional test cases from the literature for parallel-plate Poiseuille flow over collagen at both higher and lower wall shear rates, and in the presence of various anticoagulants. The predicted values agree very well with the experimental results for the training cases, and good reproduction of deposition trends and magnitudes is obtained for the heparin, but not the citrate, validation cases. The model is formulated to be easily extended to synthetic biomaterials, as well as to more complex flows. © 1999 Biomedical Engineering Society. PAC99: 8719Uv, 8710+e, 8717Aa, 8768+z, 4760+i
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  • 8
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    Annals of biomedical engineering 27 (1999), S. 525-537 
    ISSN: 1573-9686
    Keywords: Biosensors ; Mathematical model ; Algorithms ; Inverse problems ; Input estimation ; Regularization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract An approach for inference of blood glucose concentrations in real time is considered. First, a model that predicts the subcutaneous glucose concentration from the blood glucose concentration is presented. The model includes diffusive transport from the blood to the subcutaneous tissue and reactive-like cellular uptake of glucose. Next, the Phillips-Tikhonov regularization method is considered to solve the real-time input estimation problem that determines the blood glucose concentration given the subcutaneous glucose concentration. The inverse problem is regularized by imposing a smoothing condition to obtain a stable solution. Three different penalization functionals were considered in evaluating the regularization method using a synthetic function that approximates the subcutaneous glucose response to an oral glucose tolerance test in a human subject. Various levels of either white noise or time-correlated noise were superimposed onto the synthetic response to evaluate the sensitivity of the inverse to measurement error. For inversion assuming only diffusive transport, the optimal time interval of integration of previous subcutaneous measurements was found to be about 1.5/ $$\hat \alpha $$ , where $$\hat \alpha $$ -1 is the dominant time constant for the exchange of glucose between the blood and subcutaneous tissue. The optimal sampling rate was found to be 54 $$\hat \alpha $$ . Linear regularizations based on minimization of first or second derivatives of the blood glucose concentration were found to be satisfactory, each yielding a minimum error that was about 50% greater than the measurement error. Including nonlinear, reactive-like uptake of glucose was found to decrease the error magnification factor slightly. Both the model and the inverse method relating blood and subcutaneous glucose concentrations are successfully applied to experimental measurements using glucose biosensors reported by Schmidtke et al. (Proc. Natl. Acad. Sci. USA 95:294–299, 1998). © 1999 Biomedical Engineering Society. PAC99: 8780-y, 8717Aa
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  • 9
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    Annals of biomedical engineering 26 (1998), S. 166-178 
    ISSN: 1573-9686
    Keywords: ARDS ; Intravenous oxygenation ; Artificial lung ; Mathematical model ; Model ; Gas exchange ; Oxygenator
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Acute respiratory distress syndrome (ARDS) is a pulmonary edemic condition which reduces respiratory exchange in 150,000 people per year in the United States. The currently available therapies of mechanical ventilation and extracorporeal membrane oxygenation are associated with high mortality rates, so intravenous oxygenation represents an attractive, alternative support modality. We are developing an intravenous membrane oxygenator (IMO) device intended to provide 50% of basal oxygen and carbon dioxide exchange requirements for ARDS patients. A unique aspect of the IMO is its use of an integral balloon to provide active mixing. This paper describes a mathematical model which was developed to quantify and optimize the gas exchange performance of the IMO. The model focuses on balloon activated mixing, uses a lumped compartment approach, and approximates the blood-side mass transfer coefficients with cross-flow correlations. IMO gas exchange was simulated in water and blood, for a variety of device geometries and balloon pulsation rates. The modeling predicts the following: (1) gas exchange efficiency is reduced by a buildup of oxygen in the fluid near the fibers; (2) the IMO gas exchange rate in blood is normally about twice that in water under comparable conditions; (3) a balloon diameter of about 1.5 cm leads to optimal gas exchange performance; and (4) in vivo positioning can affect gas exchange rates. The numerically predicted gas transfer rates correlate closely with those experimentally measured in vitro for current IMO prototypes. © 1998 Biomedical Engineering Society. PAC98: 8710+e, 8790+y, 8265Fr
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  • 10
    ISSN: 1573-9686
    Keywords: Oxygen transport ; Microcirculation ; Cerebral circulation ; Hypoxia ; Carbon monoxide ; Mathematical model ; Computer simulation ; Anemia ; Hematocrit ; Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Cerebral blood flow (CBF) increases as arterial oxygen content falls with hypoxic (low PO2), anemic (low hemoglobin) and carbon monoxide (CO) (high carboxyhemoglobin) hypoxia. Despite a higher arterial PO2, CO hypoxia provokes a greater increase in CBF than hypoxic hypoxia. We analyzed published data using a compartmental mathematical model to test the hypothesis that differences in PO2 in tissue, or a closely related vascular compartment, account for the greater response to CO hypoxia. Calculations showed that tissue, but not arteriolar, PO2 was lower in CO hypoxia because of the increased oxyhemoglobin affinity with CO hypoxia. Analysis of studies in which oxyhemoglobin affinity was changed independently of CO supports the conclusion that changes in tissue PO2 (or closely related capillary or venular PO2) are predictive of alterations in CBF. We then sought to determine the role of tissue PO2 in anemic hypoxia, with no change in arterial and little, if any, change in venous PO2. Calculations predict a small fall in tissue PO2 as hematocrit decreases from 55% to 20%. However, calculations show that changes in blood viscosity can account for the increase in CBF in anemic hypoxia over this range of hematocrits. © 1998 Biomedical Engineering Society. PAC98: 8710+e, 8722-q, 8745Ft
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  • 11
    ISSN: 1573-9686
    Keywords: Mathematical model ; Parameter estimation ; Flow heterogeneity ; Skeletal muscle ; Glucose ; Blood flow heterogeneity ; Modeling transcapillary exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Distributed models of blood-tissue exchange are widely used to measure kinetic events of various solutes from multiple tracer dilution experiments. Their use requires, however, a careful description of blood flow heterogeneity along the capillary bed. Since they have mostly been applied in animal studies, direct measurement of the heterogeneity distribution was possible, e.g., with the invasive microsphere method. Here we apply distributed modeling to a dual tracer experiment in humans, performed using an intravascular (indocyanine green dye, subject to distribution along the vascular tree and confined to the capillary bed) and an extracellular ([3H]-D-mannitol, tracing passive transcapillary transfer across the capillary membrane in the interstitial fluid) tracer. The goal is to measure relevant parameters of transcapillary exchange in human skeletal muscle. We show that assuming an accurate description of blood flow heterogeneity is crucial for modeling, and in particular that assuming for skeletal muscle the well-studied cardiac muscle blood flow heterogeneity is inappropriate. The same reason prevents the use of the common method of estimating the input function of the distributed model via deconvolution, which assumes a known blood flow heterogeneity, either defined from literature or measured, when possible. We present a novel approach for the estimation of blood flow heterogeneity in each individual from the intravascular tracer data. When this newly estimated blood flow heterogeneity is used, a more satisfactory model fit is obtained and it is possible to reliably measure parameters of capillary membrane permeability-surface product and interstitial fluid volume describing transcapillary transfer in vivo. © 1998 Biomedical Engineering Society. PAC98: 8745Ft, 8710+e, 8722Fy
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  • 12
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    Annals of biomedical engineering 26 (1998), S. 1036-1043 
    ISSN: 1573-9686
    Keywords: Mathematical model ; Perfusion ; Diffusion ; Collagen ; Nitric oxide (NO) inhibition ; Platelet adhesion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Nitric oxide (NO) is a simple biological molecule which inhibits adhesion and aggregation of platelets. A novel NO delivery device has been developed to quantitatively study the effects of NO concentration and flux on the adhesion of platelets to a surface. The slit-flow device is lined with a protein-coated membrane through which NO gas permeates into a perfusing platelet suspension. A model predicting spatial NO concentrations and fluxes within the flow slit was validated. At a wall shear rate of 250s-1, platelet adhesion was inhibited 87% relative to controls for exposures as low as 0.1 ppm NO. Corresponding model predictions of the aqueous NO concentration and fluxes at the surface were 0.15 nM, and between 0.5 and 1.1 nanomoles cm-2 s-1, respectively. Endo-thelial cells, which release NO to inhibit platelet adhesion in vivo, generate NO at an estimated flux similar to the above values. At a NO exposure of 0.02 ppm, platelet inhibition was only 10%. The delivery device is useful for other studies in which a knowledge of the spatial NO fluxes or concentrations is desired. Knowledge of these fluxes or concentrations is beneficial towards the design of biomaterials incorporating NO to inhibit platelet adhesion. © 1998 Biomedical Engineering Society. PAC98: 8745Hw, 8722Fy, 8780+s, 8710+e, 8380Lz
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  • 13
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    Annals of biomedical engineering 26 (1998), S. 1044-1054 
    ISSN: 1573-9686
    Keywords: Lung ; Gas exchange ; Mathematical model ; O2 and CO2 transfer ; Microporous hollow fibers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract An intravascular gas exchange device for the treatment of respiratory failure consisted of a multitude of blind-ended hollow fibers glued in a pine-needle arrangement to a central gas supply catheter. It has previously been shown that gas desorption rates can be significantly enhanced by cycling gas pressure between a hypobaric level of 130 and an ambient level of 775 Torr. In this study, influences of the cycling frequency (f) and the cycle fraction during which hypobaric pressure is applied (Θ) were investigated. Rates of O2 desorption from O2-saturated water and CO2 desorption from CO2-saturated water into a manifold containing 198 fibers, 380 μm in diameter, were measured over a range of f from 0.2 to 1.0 Hz, Θ from 0.1 to 0.8, and fiber lengths from 4 to 16 cm. Relative to operation at ambient pressure, pressure cycling increased O2 transfer 3–4 times and CO2 transfer 4–6 times when the water flowed over the fiber manifold at 2.3 l/min. Transfer rates were relatively insensitive to f and Θ with 80–90% of maximum enhancement obtained when Θ was as low as 0.2. Transfer rates increased continuously with fiber length, implying that pressure cycling reduced the intra-fiber resistance to gas diffusion. A mathematical diffusion model which utilized only two adjustable parameters, a mass transfer coefficient for O2 and for CO2, simulated the trends exhibited by desorption data. © 1998 Biomedical Engineering Society. PAC98: 8745Hw, 8790+y
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  • 14
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    Annals of biomedical engineering 26 (1998), S. 911-913 
    ISSN: 1573-9686
    Keywords: Physiological database ; Mathematical model ; Physiome: microcirculation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Presented is a discussion of steps towards the creation of a database of the microcirculation encompassing anatomical and functional experimental data, and conceptual and computational models. The discussion includes issues of database utility, organization, data deposition, and linkage to other databases. The database will span levels from gene to tissue and will serve both research and educational purposes. © 1998 Biomedical Engineering Society. PAC98: 8745Ft, 8710+e, 0130Cc
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  • 15
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    Annals of biomedical engineering 26 (1998), S. 914-930 
    ISSN: 1573-9686
    Keywords: Flow distribution ; Axial diffusion ; Mathematical model ; Perfusion heterogeneity ; Relative dispersion ; Heterogeneity ; Capillary transit times ; Indicator dilution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract To mathematically model multiple indicator dilution (MID) data for the purpose of estimating parameters descriptive of indicator-tissue interactions, it is necessary to account for the effects of the distribution of capillary transit times, hc(t) In this paper, we present an efficient approach for incorporating hc(t) in the mathematical modeling of MID data. In this method, the solution of the model partial differential equations obtained at different locations along the model capillary having the longest transit time provides the outflow concentrations for all capillaries. When weighted by hc(t) these capillary outflow concentrations provide the outflow concentration versus time curve for the capillary bed. The method is appropriate whether the available data on capillary dispersion are in terms of capillary transit time or relative flow distributions, and whether the dispersion results from convection time differences among heterogeneous parallel pathways or axial diffusion along individual pathways. Finally, we show that the knowledge of a relationship among the moments of hc(t) rather than hc(t) per se, is sufficient information to account for the effect of hc(t) in the mathematical modeling interpretation of MID data. This relationship can be determined by including a flow-limited indicator in the injected bolus, thus providing an efficient means for obtaining the experimental data sufficient to account for capillary flow and transit time heterogeneity in MID modeling. © 1998 Biomedical Engineering Society. PAC98: 8745Ft, 8710+e, 0230Jr
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  • 16
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    Annals of biomedical engineering 26 (1998), S. 28-36 
    ISSN: 1573-9686
    Keywords: Mathematical model ; Tissue factor ; Wall shear rate ; FXa generation ; TF:FVIIa ; Rat ; Vascular ; Smooth muscle ; Factor X ; Coagulation ; Clot
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract A computational model was developed to investigate the contribution of classical mass transport and flow parameters to factor X (FX) activation by the tissue factor–factor VIIa complex (TF:VIIa) on one wall of a parallel-plate flow chamber. The computational results were compared to previously obtained experimental data for the generation of factor Xa (FXa) by TF:VIIa on the surface of cultured rat vascular smooth muscle cells. In this study, the complete steady-state convection–diffusion equation was solved using the commercial software package, FLUENT (Fluent Inc., Lebanon, New Hampshire). A user-defined subroutine interfaced with FLUENT implemented the surface reaction which was modeled using classical Michaelis–Menten reaction kinetics. The numerical solutions were obtained for 12 cases which used combinations of three wall shear rates and four reaction rates. The numerically obtained fluxes for a given reaction rate displayed a wall shear rate dependence which ranged from classical kinetic reaction control (no dependence) to pure diffusional control (maximum dependence). The experimental data, however, were not represented by numerical data generated using a single reaction rate. The three numerically obtained fluxes which corresponded most closely to the experimental fluxes were determined using three different V max values. This finding supports the hypothesis that there may be a direct effect of flow on the TF:VIIa complex or the cell membrane. © 1998 Biomedical Engineering Society. PAC98: 8722-q, 8710+e
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  • 17
    ISSN: 1573-9686
    Keywords: Mannitol ; Deconvolution ; Mathematical model ; Transport function ; Recirculation ; Indicator dilution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The transport function of an indicator through an organ allows the calculation of important physiological parameters, but its estimation, especially in the presence of recirculation, can be difficult. In this paper, we estimate the transport function of 3H-mannitol (an extracellular tracer of glucose) in the human leg skeletal muscle. To do so, an indicator bolus is administered into the femoral artery and its recirculating dilution curves are nonuniformly sampled in both the femoral artery and the femoral vein. A new deconvolution-based method is used to simultaneously estimate the indicator transport function and the organ plasma flow. Subsequently, the indicator mean transit time and distribution volume are calculated. The reliability of the method is assessed by Monte Carlo simulation. The ability to estimate parameters, like mean transit time and extracellular distribution volume, is critical to the study of pathophysiologic states such as diabetes, insulin resistance, and hypertension. © 1998 Biomedical Engineering Society. PAC98: 8710+e, 0270Lq, 8745Hw
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  • 18
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    Annals of biomedical engineering 26 (1998), S. 417-430 
    ISSN: 1573-9686
    Keywords: Capillary permeability ; Acute respiratory distress syndrome ; Mathematical model ; Alloxan lung injury ; Pulmonary edema ; Lung fluid balance ; Indicator dilution: optical ; Indicator dilution: radioisotope
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The objective of this study was a validation of an optical multiple indicator dilution technique for measuring microvascular exchange parameters in edematous lungs by comparison to conventional radioisotope multiple indicator dilution methods. Six anesthetized dogs were studied at baseline and after alloxan infusion to increase capillary permeability. In addition, 11 isolated, perfused dog lungs were studied at baseline and after edema was created by increasing venous pressure or by infusing alloxan to increase vascular permeability. Increased capillary permeability from alloxan infusion led to increases in most but not all capillary exchange parameters as analyzed by mathematical models and measured by both optical and radioisotope methods. Increased vascular pressure led to increased edema but no significant increases in capillary exchange parameters. Two-way analysis of variance (ANOVA; variations in baseline versus pressure or alloxan and variation in optical versus radioisotope for each transport parameter derived from the mathematical models) indicated few significant differences in capillary exchange parameters between optical and radioisotope measures. Newman–Keuls multiple comparison tests did uncover some variations between a few of the group-mean values derived from optical and radioisotope methods. However, optical and radioisotope parameter measurements were highly correlated for all studies regardless of the mathematical model used for analysis.
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  • 19
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 39 (1998), S. 469-477 
    ISSN: 0021-9304
    Keywords: poly(urethane)s ; monocyte-derived macrophages ; cholesterol esterase ; biodegradation ; biostability ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Monocytes adherent to implanted biomaterials differentiate into macrophages while synthesizing large amounts of degradative enzymes, including cholesterol esterase (CE), which previously has been shown to degrade poly(urethane)s. Human peripheral blood monocytes were cultured on tissue culture grade polystyrene (PS), and two model poly(urethane)s were synthesized from (1) polycaprolactone (PCL) and (2) polytetramethylene oxide (PTMO), both with 2,4-toluene diisocyanate (TDI) and ethylene diamine (ED). The increase in CE and total protein per cell were measured on days 8 and 28 in culture and normalized to the DNA content per cell. At day 8 there consistently were fewer cells remaining on the PTMO-based polymer than on the PCL-based polymer or the PS (p 〈 0.05). When comparing day 28 to day 8, there was more CE activity and protein per cell on all materials. However, there was a disproportionate synthesis of CE per mg of total protein on PS and TDI/PCL/ED whereas on PTMO there was not. Significantly, there was more protein and CE per cell on PTMO than on PS or TDI/PCL/ED (p 〈 0.05). This in vitro model system of the chronic phase of inflammation has shown that it is possible to culture monocytes for a month and assess the material surface itself as a potent activator of the differentiation into macrophages without secondary stimulation. Since CE has been shown to degrade poly(ether and ester)-based poly(urethane)s, the differential production of this enzyme relative to the total protein on different surfaces may impact on the potential long-term biostability of an implanted material. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 469-477, 1998.
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  • 20
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    Journal of Biomedical Materials Research 39 (1998), S. 491-497 
    ISSN: 0021-9304
    Keywords: biomaterial ; mechanism of calcification ; diffusion chamber ; calcium-containing deposits ; protein sorption ; SEM-XRMA ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In experiments in vivo using diffusion chambers, the morphology and composition of calcium-containing deposits on natural and artificial biomaterials that had no direct contact with cells were studied using scanning electron microscopy with energy dispersion X-ray microanalysis. It was revealed that the formation of a protein layer containing protein-calcium complexes is the key event in biomaterial calcification. A mechanism of formation of a calcium-containing protein matrix that creates the conditions for supersaturation of the crystal-forming medium over critical value has been proposed. The formation of nuclei of insoluble calcium phosphate starts predominantly deep in an adsorbed protein layer enriched by calcium ions. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 491-497, 1998.
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  • 21
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    Journal of Biomedical Materials Research 39 (1998), S. 511-515 
    ISSN: 0021-9304
    Keywords: dental resin ; antibacterial activity ; Streptococcus mutans ; curing ; adhesion ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In this study, the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) and an adhesion-promoting phosphoric monomer were incorporated into Bis-GMA-based dental resin and its antibacterial activity after curing was investigated. The experimental resin containing MDPB and 10-methacryloyloxydecyl dihydrogen phosphate (MDP) was polymerized and washed with methanol, and the bacteriostatic and bactericidal effects against Streptococcus mutans were determined. Growth of S. mutans was strongly inhibited by contact with the surface of cured MDPB/MDP-containing resin, although the bactericidal effect was small. Cured MDPB/MDP-containing resin also showed an inhibitory effect against in vitro plaque formation on its surface by S. mutans. The bactericide immobilized in Bis-GMA-based resin demonstrated bacteriostatic activity as a contact antimicrobial even when adhesion-promoting phosphoric monomer was incorporated into the materials. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 511-515, 1998.
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  • 22
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    Journal of Biomedical Materials Research 39 (1998), S. 531-535 
    ISSN: 0021-9304
    Keywords: artificial skin ; collagen-glycosaminoglycan matrix ; keratinocytes ; guinea pigs ; skin regeneration ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Deep skin wounds in the adult mammal close spontaneously by epithelialization, wound contraction, and scar synthesis. In previous wound healing studies, it has been unsuccessfully attempted to separate from each other the natural processes that close wounds. In this study, we attempted to isolate skin regeneration from spontaneous processes of wound closure using “island” grafts. A porous analog of the extracellular matrix, composed of a graft copolymer of type I collagen and chondroitin 6-sulfate, was seeded with uncultured autologous keratinocytes and served to induce regeneration of the dermis and the epidermis. Grafts of the copolymer, measuring 1 × 2 cm, were placed in the center of 5 × 6-cm wounds in guinea pigs. By day 14, the edges of the island grafts were clearly separated from the host epidermis and dermis by a distinct bed of granulation tissue. Histologic study of island grafts on day 14 showed that the copolymer grafts had largely degraded and that a new epidermis and dermis had been synthesized in its place. The thickness of the new epidermis increased as the density of cells seeded into the graft increased. No synthesis of epidermis or dermis was observed in the granulation tissue outside the perimeter of the island grafts. We conclude that island grafting allows the study of early events in skin regeneration in isolation from epithelialization, contraction, and scar synthesis. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 531-535, 1998.
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  • 23
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    Journal of Biomedical Materials Research 39 (1998), S. 536-538 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; drug delivery system ; anticancer agent ; methotrexate ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: An experimental study was conducted on a drug delivery system (DDS), using porous apatite ceramics (PAC): hydroxyapatite block (HAb) [Ca10(PO4)6(OH)2] having a porosity of 35-48% and pore size range of 50-300 μm, and β-tricalcium phosphate block (TCP) [Ca3(PO4)2] having a porosity of 75-80% and pore size range of 100-400 μm, for sustained release of a chemotherapeutic agent. Methotrexate (MTX) was loaded in the pores of PAC blocks by centrifuging the blocks in MTX solution. Impregnation of MTX in PAC blocks (1 cm3) was confirmed by a magnetic resonance imaging (MRI) study using Gadolinium-DTPA enhancement. The MRI showed high signal intensity in the PAC, which was confirmed by dye loading into the pores. To estimate the MTX-releasing capability of the PAC, the blocks were stored in 3 mL of phosphate-buffered saline (PBS) at 37°C and the PBS was replaced every 48 h. The amount of MTX released was assayed by high-performance liquid chromatography. This study showed that MTX-impregnated PAC (0.63-2.25 mg/block) released the drug in a steady manner and maintained its concentration (0.1-1.0 μg/mL) up to 12 days. This concentration is high enough to be effective against tumor cells. Chemotherapeutic agent-impregnated PAC, prepared by simple centrifugation, could be a valuable form of local chemotherapy when used as a strut graft to repair bone defects. This new DDS material could also be used as an adjuvant to extended curettage and provide a means to reduce the recurrence of tumors without risk of systemic toxicity. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 536-538, 1998.
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  • 24
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    Journal of Biomedical Materials Research 39 (1998), S. 120-129 
    ISSN: 0021-9304
    Keywords: polyethylene (UHMWPE) ; implant retrieval ; total hip arthroplasty ; wear ; ultrasound ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A new, in vitro ultrasound-based method to measure the thickness of acetabular polyethylene components was developed and applied to 26 uncomplicated autopsy-retrieved components and 40 unused components. The average age at total hip arthroplasty was 62 years and the average time in service of the retrieved components was 49 months. The clinical notes indicated that each of the arthroplasties was functioning well at the time of the patients death. Thickness distributions in the retrieved components had two distinct patterns. Eighteen of the retrieved components (69%) had their thinnest areas self-contained and located near the polar point. In the other 8 retrieved components (31%) the areas of minimum thickness were adjacent to the rim. Thickness distribution in the unused cups was predominately concentric with the thinnest area located near the polar point (85% of the cups). Detection limits for dimensional change were established based on the variability found in the unused liners. Fifteen of the 26 retrieved components (58%) had areas of reduced thickness which exceeded the detection limits; the average thickness reduction rate for these components was 0.076 mm per year. The other 11 retrieved components (42%) lacked such areas. The 15 cups with areas of reduced thickness had a longer time in service (63 ± 18 months) than the 11 cups without areas of reduced thickness (32 ± 25 months) (p = 0.003), but no other clinical factor (age, gender, Harris hip score, size and inclination of the cup, type of femoral fixation) was associated with these 15 cups. Cylindrical models to estimate volumetric change tended to underestimate the actual changes, suggesting that the actual particulate burden may be greater than previously appreciated.Finding that the pattern of thickness reduction can vary suggests that distinctive hip loading modes may be present postoperatively in patients with total hip arthroplasty. The wear rates of these components are consistent with wear rates calculated from radiographic data for well-functioning implants and are considerably lower than wear rates calculated for surgically-retrieved implants, indicating that autopsy-derived retrievals may be more representative of the majority of components currently in service than surgically-derived retrievals. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 120-129, 1998.
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  • 25
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    Journal of Biomedical Materials Research 39 (1998), S. 234-243 
    ISSN: 0021-9304
    Keywords: ceramics ; calcium phosphates ; surface reactions ; surface transformations ; in vitro ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Changes occurring at the surface of a calcium phosphate coating when in contact with osteoblasts versus those in acellular solutions were analyzed. The coating studied is one with a well-documented extensive effect on short-term bone growth stimulation. Precipitates associated with original crystals and organized in a weblike structure were observed after a 3-week culture with osteoblasts. The precipitates were identified as carbonated hydroxyapatite (c-HA). In contrast, no significant surface changes were detected after immersion in an acellular serum-containing solution. However, in an acellular serum-free solution simulating the ionic composition of plasma, precipitates, identified as c-HA, were abundantly formed. Dissolution of the original coating preceded precipitation. The data support the hypothesis that dissolution of synthetic calcium phosphate ceramics is an initial step in their transformation to a biologically equivalent apatite, and suggest that both solution-mediated (dissolution-precipitation) and cell-mediated mechanisms are involved in the surface transformation. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 234-243, 1998.
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  • 26
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    Journal of Biomedical Materials Research 40 (1998), S. 214-223 
    ISSN: 0021-9304
    Keywords: ultra-high-molecular-weight polyethylene ; composites ; creep ; time-temperature superposition ; viscoelastic properties ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The short- and long-term creep behaviors of ultra-high-molecular-weight polyethylene (UHMWPE) systems (compression-molded UHMWPE sheets and self-reinforced UHMWPE composites) have been investigated. The short-term (30-120 min) creep experiment was conducted at a load of 1 MPa and a temperature range of 37-62°C. Based on short-term creep data, the long-term creep behavior of UHMWPE systems at 1 MPa and 37°C was predicted using time-temperature superposition and analytical formulas. Compared to actual long-term creep experiments of up to 110 days, the predicted creep values were found to well describe the creep properties of the materials. The creep behaviors of the UHMWPE systems were then evaluated for a creep time of longer than 10 years, and it was found that most creep deformation occurs in the early periods. The shift factors associated with time-temperature superposition were found to increase with increasing temperature, as per the Arrhenius equation. The effects of temperature, materials, and load on the shift factors could be explained by the classical free volume theory. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 214-223, 1998
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  • 27
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    Journal of Biomedical Materials Research 40 (1998), S. 275-281 
    ISSN: 0021-9304
    Keywords: polysaccharides ; DTAF labeling ; radiolabeling ; smooth-muscle cells ; confocal analysis ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Glycosaminoglycans (GAGs) such as heparan sulfates are complex carbohydrate polymers. These structural components of the extracellular matrix are essential for the adhesion, migration, and regulation of cellular growth. To understand the physiological role of GAGs and GAG analogues, a practical approach consists of labeling and detecting them in cell extracts, or analyzing binding domains and their distributions into the cells. We propose a convenient and reliable method for preparing and labeling amino-enriched polysaccharides with the fluorescent derivative 5-[(4,6-dichlorotriazine-2-yl)amino]-fluorescein (DTAF). Radioiodination is then performed on the DTAF moiety. This method was applied to polysaccharides known to inhibit vascular smooth-muscle cell (SMC) proliferation such as functionalized dextrans derived from poly(α1-6 glucose) and fucan, poly(L-fucose 4-sulfate) extracted from brown seaweed. Using autoradiography and confocal microscopy, we observed the fixation and internalization of labeled antiproliferative products in SMCs from rat aorta. These probes can be useful for the understanding of polysaccharide-cell interactions. In addition, the method presented here can be applied to various synthetic or natural biomedical materials. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 275-281, 1998.
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  • 28
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    Journal of Biomedical Materials Research 39 (1998), S. 351-357 
    ISSN: 0021-9304
    Keywords: silk fibroin ; arginyl residues ; chemical modification ; cell attachment ; cell growth ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: We prepared matrices of Bombyx mori silk fibroin (SF) with different degrees of modification of arginyl residues by reaction between 1,2-cyclohexanedione (CHD) and SF. Two kinds of SF, namely native SF (NSF), obtained from the silk gland of silkworm larvae, and regenerated SF (RSF), prepared from cocoons of the same silkworm, were used in this study because their amino acid compositions were slightly different from each other. The attachment and growth of mouse fibroblast (L-929) cells on the matrices of the NSF and RSF, in which half or almost all of the arginyl residues were modified (NSF50, RSF50, NSF100, and RSF100), were studied using a cell culture method. Both NSF50 and NSF100 exhibited higher cell attachment than did the unmodified NSF. While the cell growth on NSF50 was not significantly different from that on NSF and NSF100, the growth on NSF100 was higher than that on NSF. The cells attached to NSF50 and NSF100 were extensively spread out and their filopodia were visible by SEM. The cell attachment and growth on RSF were comparable to those on NSF100. Although RSF50 exhibited almost the same cell attachment as did the unmodified RSF, RSF100 exhibited a lower cell attachment than did the unmodified RSF and RSF50. There were no significant differences in the cell growth among RSF series. The cells attached to RSF50 and RSF100 aggregated to form masses, and their filopodia could not be found. The relationship of cell attachment to the basicity of the substrate is considered because the modification of the positively charged arginyl residue changed the basicity of the substrate and the cell attachment on the substrate. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 351-357, 1998.
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  • 29
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    Journal of Biomedical Materials Research 39 (1998), S. 364-372 
    ISSN: 0021-9304
    Keywords: dense HA implant ; HA-coated implant ; push-out test ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Two types of hydroxyapatite (HA) implants have been developed: an HA-coated implant and a dense HA implant. For a longer in situ life span, the HA implant must remain chemically stable and possess high resistance to occlusal force. To determine which type of HA implant shows better durability, this comparative dog study was done to evaluate push-out test results of HA-coated implants and dense HA implants of approximately the same size after implantation in the mandibular and coxal bones for periods ranging from 3 weeks to 10 months. The findings revealed that for the mandibular implants, the push-out values of HA-coated implants were significantly higher than those of dense HA implants at 2 and 4 months after implantation, with significance levels of p 〈 .001 and p 〈 0.05, respectively. However, there was no significant difference between the two implant types at 10 months. As for the coxal implants, no significant differences were noted for any period. Furthermore, the ratio of push-out values of the dense HA implants to those of the HA-coated implants situated in the same position bilaterally in each bone of the body for each implantation period rose with the passage of time, especially in the mandible. In the mandibular implants, the correlation coefficient of the relationship between the ratio and duration of implantation was highly significant (p 〈 0.001). Push-out testing caused detachment of the surface portion of the HA coating that was bound to the dense bone from the HA-coated implant at 2, 4, and 10 months after implantation. Furthermore, at 10 months the HA-coated layer in the wide areas of the implants had completely detached from the metal substrate, in contrast to the dense HA implants, which remained durable throughout the test period. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 364-372, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 371-377 
    ISSN: 0021-9304
    Keywords: osteoblast ; adhesion ; peptide ; integrin ; heparan sulfate ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Proactive, “next generation” dental/orthopedic biomaterials must be designed rationally to elicit specific, timely, and desirable responses from surrounding cells/tissues; for example, such biomaterials should support and enhance osteoblast adhesion (a crucial function for anchorage-dependent cells). In the past, integrin-binding peptides have been immobilized on substrates to partially control osteoblast adhesion; the present study focused on the design, synthesis, and bioactivity of the novel peptide sequence Lys-Arg-Ser-Arg that selectively enhances heparan sulfate-mediated osteoblast adhesion mechanisms. Osteoblast, but not endothelial cell or fibroblast, adhesion was enhanced significantly (p 〈 0.05) on substrates modified with Lys-Arg-Ser-Arg peptides, indicating that these peptides may be osteoblast- or bone cell specific. Blocking osteoblast cell-membrane receptors with various concentrations of soluble Arg-Gly-Asp-Ser peptides did not inhibit subsequent cell adhesion on substrates modified with Lys-Arg-Ser-Arg peptides, providing evidence that osteoblasts interact with Arg-Gly-Asp-Ser and with Lys-Arg-Ser-Arg peptides via distinct (i.e., integrin- and proteoglycan-mediated) mechanisms, each uniquely necessary for osteoblast adhesion. The present study constitutes an example of rational design/selection of bioactive peptides, confirms that osteoblast adhesion to substrates can be controlled selectively and significantly by immobilized peptides, and elucidates criteria and strategies for the design of proactive dental/orthopedic implant biomaterials. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 371-377, 1998.
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    Journal of Biomedical Materials Research 39 (1998), S. 415-422 
    ISSN: 0021-9304
    Keywords: bacterial adherence ; Staphylococcus epidermidis ; dye elution ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The ability to adhere to materials and promote formation of a biofilm is an important feature of the pathogenicity of some organisms, most notably the coagulase negative staphylococci. Various methods to detect bacterial adherence are available, but detection of adherence to nontransparent materials can be difficult. It was the purpose of this study to establish the suitability of a dye elution technique to detect adherence. The technique involves fixing the bacterial film with formalin, staining with crystal violet, eluting the dye with ethanol, and determining the optical density of the solution using 96-well plates and an enzyme immunosorbent assay reader with a 540-nm filter. This technique distinguished a known adherent from a known nonadherent organism and demonstrated that the presence of protein can inhibit adherence, and that adherence of different organisms to different biomedically important polymers can be measured. The dye elution technique was used to evaluate the adherence of known slime-producing polysaccharide antigen-positive (PSA+) and known nonslime-producing polysaccharide antigen-negative (PSA-) Staphylococcus epidermidis organisms to implant grade materials (polyethylene, expanded polytetrafluoroethylene, Dacron, silicone, and collagen) as well as to polystyrene. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 415-422, 1998.
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  • 32
    ISSN: 0021-9304
    Keywords: surface topography ; plasma etching ; cellular orientation ; focal adhesion point ; in vitro ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: During this study, microtechnology and plasma etching were used to produce gratings 1.0 (TiD01), 2.0 (TiD02), 5.0 (TiD05), and 10.0 μm wide (TiD10) into commercially pure titanium wafers. After incubation of rat dermal fibroblast (RDFs) on these surfaces for 3 days, the cells were observed with scanning electron (SEM), transmission electron (TEM), and confocal laser scanning microscopy (CLSM). Results showed that the RDFs as a whole and their stress fibers oriented strictly parallel to the surface pattern on the TiD01 and TiD02 surfaces. On the TiD05 and TiD10 surfaces, this orientation was not observed. In addition, TEM and CLSM demonstrated that the focal adhesion points (FAP) were located mainly on the surface pattern ridges. TEM revealed that FAP were wrapped occasionally around the edges of the ridges. Only the RDFs on both the TiD05 and TiD10 surfaces protruded into the grooves and possessed FAP on the walls of the grooves. Attachment to the groove floor was observed only on the TiD10 textures. Comparison of these results with earlier observations on microtextured silicone rubber substrata suggests that material-specific properties do not influence the orientational effect of the surface texture on the observed RDF cellular behavior. The proliferation rate of the RDFs, however, seems to be much higher on titanium than on silicone rubber substrata. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 425-433, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 458-463 
    ISSN: 0021-9304
    Keywords: adhesion mechanism ; dentin primer ; N-methacryloyl glycine ; dentinal collagen ; prolylprolylglycyl oligomer ; 13C-NMR ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The origin of the pH-dependent bond strength of the resin to etched dentin treated with N-methacryloyl glycine (NMGly) primer was studied by 13C-nuclear magnetic resonance (NMR) including spin-lattice relaxation time, T1, observation. When the dentinal collagen was suspended in the NMGly solution at pH = 1.6, the T1 values of all the carbons attributed to the NMGly species were significantly decreased. This indicated the presence of an interaction between the NMGly and the dentinal collagen. To obtain detailed information of this interaction, the 13C-NMR spectra of the NMGly were measured in the presence of the model compound for the collagen, (Pro-Pro-Gly)5 at pH = 1.7. The 13C-NMR peaks of the carbonyl carbons of the amide and carboxylic acid in the NMGly species shifted to a higher field and the T1 values decreased. Furthermore, when the molar ratio of (Pro-Pro-Gly)5 to NMGly was decreased from 1:1 to 1:3, the T1 values of the carbonyl carbon attributed to the carboxylic acid in the C-terminal Gly residue of the oligopeptide decreased dramatically. It can be construed that this indicated the formation of a hydrogen bond between the amide, -NH and the carboxylic acid of the NMGly species and the carboxylic acid of the C-terminal Gly residue of the oligopeptide. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 458-463, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 498-509 
    ISSN: 0021-9304
    Keywords: protein adsorption ; grafted PEO ; reflectivity ; star polymers ; end-functional polymers ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Four different poly(ethylene oxide) [PEO] molecules were compared as grafted polymer layers for biomaterials' substrates: two linear polymers and two star polymers. Conditions maximizing surface coverage for each molecule were employed with the aim of inhibiting protein adsorption and increasing the density of end groups. Neutron reflectivities of the grafted layers immersed in deuterium oxide (heavy water) were measured and used to calculate volume fraction profiles of the polymer as a function of distance from the surface. These density profiles were combined with protein adsorption data on the grafted layers to compare with recent theoretical and experimental studies of protein resistance by PEO at surfaces. We found that the grafting density is maximized by coupling the linear PEO from a K2SO4 salt buffer, which is a poor solvent for PEO. However, the grafting density of star PEO was maximized when no K2SO4 was used and the stars were dissolved near the overlap concentration. Concentration profiles obtained from the reflectivity data show that the hydrated polymers swell to ∼ 10 times the dried layer thickness and exhibit a low density (maximum volume fractions 〈 0.4 PEO) throughout the layer. The PEO surfaces obtained with both the star and linear polymers resisted adsorption of cytochrome-c and albumin except for a small amount of cytochrome-c adsorption on the short, many-armed star polymer surface. A hypothesis of adsorption on the star polymer layer is presented and criteria for controlling receptor-mediated cell-substrate interactions by ligand-modified chain ends are discussed. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 498-509, 1998.
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  • 35
    ISSN: 0021-9304
    Keywords: atomic force microscope (AFM) ; dentin ; collagen ; viscoelasticity ; mechanical properties ; elastic modulus ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Using an atomic force microscope (AFM) with an attachment specifically designed for indentation, we measured the mechanical properties of demineralized human dentin under three conditions: in water, in air after desiccation, and in water after rehydration. The static elastic modulus (Ehr = 134 kPa) and viscoelastic responses (τε = 5.1 s and τσ = 6.6 s) of the hydrated, demineralized collagen scaffolding were determined from the standard linear solid model of viscoelasticity. No significant variation of these properties was observed with location. On desiccation, the samples showed considerably larger elastic moduli (2 GPa), and a hardness value of 0.2 GPa was measured. Upon rehydration the elastic modulus decreased but did not fully recover to the value prior to dehydration (381 kPa). © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 539-544, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 567-576 
    ISSN: 0021-9304
    Keywords: biocompatibility ; erodible polymer ; fibroblast growth factor-2 ; osteogenesis ; polylactide-polyglycolide ; porous ingrowth ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The effects of recombinant human fibroblast growth factor-2 (rhFGF-2) in the presence of eroding 50:50 poly(DL-lactide-co-glycolide) (PDLLG) on acute bone healing were studied in the optical bone chamber (BCI). BCIs were loaded with disks of PDLLG surrounded by one of four rhFGF-2 doses. Fifty-two female rabbit right tibias were implanted. Commencing the third week post implantation (W3) healing in the BCI compartment was observed weekly, using intravital microscopy, until W8. The doses were: unloaded, loaded with polymer only, and polymer plus 0.5, 1.0, and 10 μg rhFGF-2. Videotaped and photographed bone images were measured and analyzed using a frame-grabber digitizing system. Comparison with controls revealed that ossification rates were significantly above normal in rabbits loaded with polymer plus any of the rhFGF-2 doses. Comparison with polymer-only BCIs showed that PDLLG plus any of the three rhFGF-2 doses was linked with ossification rates significantly higher than baseline. The results indicated that FGF-2 in the dose range studied effectively can overcome the retarding effects of eroding polymer on ossification that has been reported by this laboratory. Interpretation of the retarding effects of the polymer disks, although consistent with previously studied washer-shaped devices of the same material, was complicated by a difference in erosion rate. This result supports the notion that erodible device geometry is a major factor in determining biocompatibility and must be considered in the design of carriers. Accordingly, programming of dose specificity for delivering a given polypeptide cytokine to a given host site must allow for the inhibitory effects of an eroding carrier and the influence of device geometry on these effects and erosion. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 567-576, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 598-605 
    ISSN: 0021-9304
    Keywords: tissue response ; implants ; sensors ; vascularity ; foreign-body response ; subcutaneous implants ; PVA ; PTFE ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The results of two previous studies have shown that implant porosity can be used to increase both the measured diffusion coefficients and the vascularity within the tissue encapsulating long-term subcutaneous implants. This study investigates the hypothesis that the analyte concentrations within the tissue surrounding porous implants will respond more quickly to changes in plasma levels than does the densely packed, avascular fibrous capsule surrounding nonporous implants. The average concentration of lissamine-rhodamine was measured in tissue within 100 μm of the following implants at four different times following injection of the tracer: PVA-skin, PVA-5, PVA-60, PVA-700 (polyvinyl alcohol nonporous, 5 μm, 60 μm, and 700 μm mean pore sizes, respectively) and PTFE-0.5 and PTFE-5 (polytetrafluoroethylene 0.5 μm and 5 μm mean pore sizes, respectively). The results were compared to those of unimplanted subcutaneous tissue (SQ). In addition, the data were analyzed with a simple two-compartment model in which a tissue response time constant (τp) was extracted. As in the case of vascular density, the cellular dimension of the PVA-60 pore sizes produced surrounding tissue with the optimum response times to changes in plasma concentrations. The concentrations of rhodamine within the tissue surrounding the PVA-60 implant were the highest at all time points and responded to the change in plasma rhodamine concentration approximately three times more quickly (τp = 764 s) than the fibrous tissue encapsulating the nonporous PVA-skin (τp = 2058 s) and more than twice as quickly as SQ (τp = 1627 s). The overall mass transfer rate between plasma and the tissue surrounding the different implants calculated from the permeability and density of vessels from the previous study correlated very well (r2 = 0.7, p 〈 .02, slope of 0.98) with the reciprocal of the tissue response time constant (τp). © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 598-605, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 640-645 
    ISSN: 0021-9304
    Keywords: tetracalcium phosphate ; calcium phosphate cement ; Raman spectroscopy ; FT-IR spectroscopy ; setting reaction ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Polycrystalline tetracalcium phosphate (TTCP), a material of considerable interest for human implantation due to its similarity to hydroxyapatite, was studied by means of Raman and FT-IR spectroscopy. The spectra were interpreted on the basis of group theoretical considerations. In addition, the setting reaction of a calcium phosphate cement (CPC) consisting of an equimolar mixture of TTCP and dicalcium phosphate (DCPA) was investigated by Raman spectroscopy. The band of the totally symmetric phosphate mode ν1 of TTCP showed marked factor group splittings. The splitting components arose at coincident wave numbers in the IR and Raman spectra. This observation was in accordance with space group P21 (factor group C22, Z = 4). The characteristic splitting of ν1 allowed the setting reaction of CPC to hydroxyapatite to be followed. According to the Raman spectroscopic results, considerable amounts of TTCP must be present at the sample surface after 24 h of setting in an aqueous environment. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 640-645, 1998.
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  • 39
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    Journal of Biomedical Materials Research 40 (1998), S. 233-243 
    ISSN: 0021-9304
    Keywords: corrosion ; impedance spectroscopy ; titanium ; Co-Cr-Mo ; platinum ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: A novel test method is presented whereby the polarization behavior and impedance characteristics of an electrochemical interface can be determined simultaneously from potential-step current transient responses. In this test, small incremental steps in potential are applied to an electrochemical interface and the current transient response is collected digitally. Then, the data are subjected to a numerical Laplace transform technique to obtain the frequency-dependent admittance (reciprocal impedance) of the interface. From this analysis, several interesting and relevant parameters, including the high- and low-frequency resistances, interfacial capacitance, and polarization behavior, can be obtained. The mathematical basis for this technique is presented and the methodology is applied to three implant alloys (titanium, Co-Cr-Mo, and platinum). Electrochemical tests were performed in 0.9% NaCl at room temperature. Starting at an initial negative potential, the samples were stepped in 50-mV increments every 10 or 100 s up to a maximum potential and then reversed back to the starting potential. The impedances were calculated and used to evaluate the behavior. From these tests, one can determine the potential dependence of the oxide film thickness as well as the changes in the underlying electrochemical state of the interfaces with potential. This technique is inexpensive and easily applied to any electrochemical system, and yields significantly more electrochemical information than either anodic polarization or electrochemical impedance spectroscopy alone. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 233-243, 1998.
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  • 40
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    Journal of Biomedical Materials Research 39 (1998), S. 498-505 
    ISSN: 0021-9304
    Keywords: phase-separated polymer ; polymer-conjugated proteins ; poly(NIPAAm) ; trypsin ; enzyme activity ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Reversible soluble-insoluble oligomer-enzyme conjugates have been prepared by conjugating a thermally sensitive oligomer, poly(N-isopropylacrylamide) [poly(NIPAAm)] to trypsin. The conjugates can catalyze enzymatic reactions in solution and then may be separated from the solution by thermal precipitation. One special feature of the conjugates is that every poly(NIPAAm) chain has only one end attachment to the enzyme, so that the loss of enzymatic activity due to steric hindrance should be minimized. Conjugates with various numbers of oligomer chains per trypsin molecule were prepared. Surprisingly, the conjugates increased in enzymatic activity with increasing oligomer conjugation to the native trypsin. The trypsin active sites in the conjugates were accessible to large molecules, such as soybean trypsin inhibitor (MW = 21,500). The enzyme conjugates were more stable than native trypsin, both in solution and in the precipitated phase. On the other hand, the conjugates lost enzymatic activity faster than native trypsin when the temperature was repeatedly cycled through the lower critical solution temperature (LCST) of the poly(NIPAAm). The recovery of the conjugates by thermal precipitation in each cycle was over 95% even after 14 cycles through the LCST. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 498-505, 1998.
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    Journal of Biomedical Materials Research 39 (1998), S. 524-530 
    ISSN: 0021-9304
    Keywords: magnetron sputtering ; calcium phosphates ; hydroxyapatite ; carbonate apatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Radiofrequency magnetron sputter deposition was used to deposit Ca-P sputter coatings on titanium discs, and these coatings were implanted subcutaneously into the backs of rabbits. Half of the as-sputtered coatings were subjected to additional heat treatment for 2 h at 500°C. X-ray diffraction (XRD) demonstrated that annealing at 500°C changed the amorphous sputtered coating into an amorphous-crystalline apatite structure. Scanning electron microscopic (SEM) examination of the sputtered coatings showed excellent coverage of the substrate surface. Annealing of the 4-μm-thick coatings resulted in the appearence of small cracks. SEM demonstrated that until 4 weeks of implantation, all heat-treated coatings were present and all amorphous coatings were completely or mostly dissolved. Fourier transform infrared spectroscopy showed the formation of carbonate apatite (CO3-AP) on these specimens. Furthermore, XRD analysis showed that these CO3-AP precipitated coatings disappeared after 8 weeks of implantation. On the other hand, SEM inspection of these specimens revealed that the 4-μm heat-treated coating was still partially maintained and that small Ca-P crystals were present on the titanium substrate. On the basis of these results, we conclude that apparently 0.1 μm heat-treated Ca-P sputter coating is of sufficient thicknesses to stimulate carbonate apatite deposition under in vivo conditions. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 524-530, 1998.
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  • 42
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    Journal of Biomedical Materials Research 39 (1998), S. 539-548 
    ISSN: 0021-9304
    Keywords: cytokine delivery via covalent binding ; tissue repair ; biomaterials ; collagen ; transforming growth factor β ; polyethylene glycol ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To overcome rapid diffusion and clearance from the implant site and to increase stability, recombinant transforming growth factor β2 (TGF-β2) was covalently bound to injectable bovine dermal fibrillar collagen (FC) and its activity compared to admixed TGF-β2. Covalent binding was achieved in a two-step procedure: First, TGF-β2 was reacted with the difunctional polyethylene glycol (PEG) linker, and then the PEG-attached TGF-β2 (PEG-TGF-β2) was bound to the fibrillar collagen (FC-PEG-TGF-β2). Initial binding of TGF-β2 to difunctional succinimidyl glutarate (D-SG-PEG) or succinimidyl propionate polyethylene glycol (D-SE-PEG) linkers was completed after reacting for 8 or 10 min as monitored by reverse-phase high-performance liquid chromatography. After reaction with injectable fibrillar collagen, extraction of unbound PEG-TGF-β2 and Western blot analysis, using a TGF-β specific antibody, demonstrated that at least 85% of the TGF-β2 was bound to the fibrillar collagen. The activity of PEG-TGF-β2 was fully stable in phosphate-buffered saline at 4°C and 37°C for at least up to 4 weeks. Unmodified TGF-β2 mixed with fibrillar collagen was completely inactivated after 1 week of incubation, as measured by the mink lung epithelial cell (Mv1Lu) growth inhibition assay. Formulations of FC-PEG-TGF-β2 containing 40 μg/mL TGF-β2 were implanted subcutaneously into rats and analyzed after days 7, 21, and 42. All TGF-β2-containing formulations showed the TGF-β typical fibroblastic response at the day 7 time point. Covalent binding of TGF-β2 to collagen with both difunctional PEG crosslinkers resulted in a significantly stronger and longer-lasting TGF-β2 response than that observed with admixed formulations of collagen and TGF-β. The TGF-β response with FC-PEG-TGF-β2 lasted up to day 42 but was not seen after day 7 for TGF-β2 admixed to FC. These findings clearly demonstrate that TGF-β2 remains fully active after being covalently bound to collagen via difunctional PEG. In addition, covalent binding potentiates and prolongs in vivo TGF-β responses and stabilizes the TGF-β in vitro. Results suggest that this method of formulation could be useful to stabilize and deliver similar peptide growth factors or biologically active agents. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 539-548, 1998.
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  • 43
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    Keywords: biomaterial ; bioprostheses ; suture ; pericardium ; heart valves ; Chemistry ; Polymer and Materials Science
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    Topics: Medicine , Technology
    Notes: The mechanical behavior of calf pericardium employed in the manufacture of cardiac bioprostheses was assessed according to the region from which it was selected. For this purpose, selected samples of the tissue were sewn with different types of commercially available sutures and subjected to tensile testing, the results of which were compared with the findings in selected, but not sutured, tissue used as a control. The results confirm a loss of resistance - that is, a reduction of the capacity of sutured samples of the biomaterial to withstand breakage stress compared with control samples. Taking into account the marked resistance to breakage of the suture thread, this phenomenon can only be explained as a consequence of the deleterious mechanical interaction between the suture and chemically treated pericardium. This interaction is illustrated by the shearing force which is responsible for the loss of resistance in the tested samples. These trials demonstrate that the results can be improved and the deleterious interaction diminished, although not eliminated, when the pericardium is selected from a given region. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 568-574, 1998.
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    Journal of Biomedical Materials Research 39 (1998), S. 603-610 
    ISSN: 0021-9304
    Keywords: sintered carbonate apatite ; osteoclasts ; bioresorption ; bioresorbable bone substitutes ; acid dissolution ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: The dissolution behavior of sintered carbonate apatite was investigated in a 10 mM/L acetic acid solution adjusted to pH 5.0 at 37°C, and compared to that of sintered hydroxyapatite and bone apatite for the purpose of establishing some similarities between the physicochemical dissolution of apatite biomaterials in vitro and their ability to be resorbed by osteoclasts in vivo. Both the sintered carbonate apatite and the bone apatite dissolved to an appreciable extent. Their solution compositions changed in an almost identical manner until toward the end of the reaction. The solution compositions for sintered carbonate apatite at 30 s was comparable with that for sintered hydroxyapatite at 3.8 days with respect to the degree of supersaturation, indicating that the former specimen is much more soluble than the latter specimen. Osteoclasts which were obtained from the long bones of 1-day-old neonatal rabbits resorbed bone and sintered carbonate apatite, but not sintered hydroxyapatite. These findings suggest that sintered carbonate apatites, which have characteristics that can be favorably compared with those of bone, especially with respect to its reactivity to acid media, would be useful as bioresorbable bone substitutes. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 603-610, 1998.
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    Journal of Biomedical Materials Research 39 (1998), S. 630-636 
    ISSN: 0021-9304
    Keywords: epoxide ; collagen ; polyurethane ; cellular growth ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The current study investigated the effects of vary epoxides on linking capacity of collagen to carboxyl-group-enriched polyurethane (PU) and the consequent effects on the growth of endothelial cells. Epoxides of EX-810, 1,4BDE, DER732, DER331, and DER332 were initially reacted with the carboxyl groups of PU substrates at 110°C for 20 h. Free epoxy rings of epoxide-PU substrates, characterized by Fourier transform infrared spectroscopy and quantified by titration with HCl and NaOH, were available for collagen grafting. The amounts of collagen grafted were in accordance with the amounts of free epoxy rings detected and correlated with the growth of endothelial cells on the substrates. Our results indicated that epoxides with shorter aliphatic intermediate chain can graft more collagen to the epoxide-PU substrates than epoxides with longer intermediate chain or with aromatic groups. Epoxides were also demonstrated to be nontoxic linking agents for biomaterials. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 630-636, 1998.
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    Journal of Biomedical Materials Research 39 (1998), S. 660-666 
    ISSN: 0021-9304
    Keywords: injectable bone substitute ; biphasic calcium phosphate ; cellulose derivatives ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: The purpose of this study was to develop an injectable bone substitute (IBS) for percutaneous orthopedic surgery. The multiphasic material used was composed of a 2% aqueous solution of methylhydroxypropylcellulose (MHPC) and biphasic calcium phosphate (BCP, 60% hydroxyapatite and 40% β-tricalcium phosphate) in which MHPC served as the carrier for 80-200 μm of BCP granules. The best BCP/polymer ratio was determined by the rheological properties and higher BCP content of the material. Steam sterilization was more effective than gamma irradiation in maintaining the stability of the mixture and conserving its physiochemical and mechanical properties. The in vitro biocompatibility of the composite was checked by direct-contact cytotoxicity and cell-proliferation assays. A preliminary in vivo test was performed in the rabbit using intraosseous implantations in the femoral epiphysis. Histological analysis was done after 1, 2, 4, and 10 weeks. Bone ingrowth into the IBS, in close association with BCP granules, was observed after 1 week and increased regularly from the surface inward at 2, 4, and 10 weeks. At the same time, smaller BCP granules (less than 80 microns in diameter) were degraded and resorbed. This injectable biomaterial proved suitable for cavity filling. The water solubility and viscosity of the polymer allow cells to recolonize, with in situ bonding of the mineral phase © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 660-666, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 24-30 
    ISSN: 0021-9304
    Keywords: protein adsorption ; ceramic ; albumin ; IgG ; fibrinogen ; fibronectin ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Ceramics seldom have been used as blood-contacting materials. However, alumina ceramic (Al2O3) and polyethylene are incorporated into the pivot bearings of the Gyro centrifugal blood pump. This material combination was chosen based on the high durability of the materials. Due to the stagnant flow that often occurs in a continuous flow condition inside a centrifugal pump, pivot bearing system is extremely critical. To evaluate the thombogenicity of pivot bearings in the Gyro pump, this study sought to investigate protein adsorption, particularly albumin, IgG, fibrinogen, and fibronectin onto ceramic surfaces. Al2O3 and silicon carbide ceramic (SiC) were compared with polyethylene (PE) and polyvinylchloride (PVC). Bicinchoninic acid (BCA) protein assay revealed that the amount of adsorbed proteins onto Al2O3 and SiC was significantly less than that on PVC. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated that numerous proteins adsorbed onto PVC compared to PE, Al2O3, and SiC. Identification of adsorbed proteins by Western immunoblotting revealed that the adsorption of albumin was similar on all four materials tested. Western immunoblotting also indicated lesser amounts of IgG, fibrinogen, and fibronectin on Al2O3 and SiC than on PE and PVC. In conclusion, ceramics (Al2O3 and SiC) are expected to be thromboresistant from the viewpoint of protein adsorption. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 24-30, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 57-65 
    ISSN: 0021-9304
    Keywords: cell adhesion ; avidin-biotin ; endothelialization ; vascular grafts ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Binding between the protein avidin and the vitamin biotin was used as an extrinsic, high affinity receptor-ligand system to augment the intrinsic integrin-dependent cellular adhesion mechanism. Glass substrates were coupled with avidin receptors through an adsorbed film of biotinylated bovine serum albumin (b-BSA). The avidin-treated slides then were seeded with biotinylated bovine aortic endothelial cells (BAEC). A 3:1 ratio of BSA:b-BSA provided the best results in terms of specific cellular attachment, growth, and spreading. Control surfaces consisted of bare glass or glass with adsorbed BSA. Attachment of unmodified BAEC to glass decreased in the presence of anti-β1 integrin antibody. Adhesion of biotinylated BAEC to avidin-treated slides was not affected by anti-β1 integrin antibody, consistent with integrin-independent avidin-mediated adhesion. The initial rate of cell spreading was greatest for avidin-biotin-mediated adhesion (80.0 ± 25.6 μm2/h), followed by integrin-dependent cellular adhesion on plain glass (35.7 ± 7.7 μm2/h) and, finally, by adhesion on BSA-coated protein surfaces (10.2 ± 0.3 μm2/;h). Biotinylated and unmodified BAEC, cultured for 1 h in serum-containing media, were subjected to laminar flow in a variable-height flow chamber that provided a range of shear stresses from 0.2 to 75 dynes/cm2. The critical shear stress required to detach 50% of the cells in serum-containing media increased from 4.6 ± 0.8 dynes/cm2 for integrin-dependent adhesion to 12.6 ± 1.2 dynes/cm2 for avidin-biotin-mediated adhesion. Avidin-mediated attachment for biotinylated BAEC increased initial cellular spreading rates and strength of attachment (i.e., at 1 h) by a factor of two and three, respectively. These results support the hypothesis that integrin-mediated cell attachment and spreading can be enhanced using high affinity integrin-independent binding. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 57-65, 1998.
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  • 49
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    Journal of Biomedical Materials Research 40 (1998), S. 92-103 
    ISSN: 0021-9304
    Keywords: blood ; plasma ; coagulation ; mathematical model ; anticoagulation ; thrombin ; thrombin ligand ; DNA ligands ; aptamers ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A biophysical model linking fibrin polymerization kinetics (following release from a thrombin-fibrinogen complex), coagulation time, and competitive inhibition of thrombin illustrates the utility of thrombin-binding ligands as anticoagulants in blood collection applications. The resulting mathematical relationship connecting fibrinogen, ligand, and thrombin concentrations was tested against experimentally observed anticoagulation of whole, platelet-poor porcine plasma induced by short, single-stranded DNA oligonucleotides originally found to bind thrombin by screening combinatorial libraries. The thrombin-fibrinogen dissociation constant Ks served as the single adjustable parameter in a least-squares fitting of the model to experimental anticoagulation data. Best-fit Ks values corroborated μM values measured in plasma-free systems, and application of the model to a ligand challenge to the intrinsic pathway of plasma coagulation corroborated nM endogenous thrombin concentrations measured in porcine blood activated by endotoxin insult in vivo. The model fit to data suggests that only about 20% conversion of blood fibrinogen to fibrin is required to coagulate (gel) porcine plasma. This prediction is consistent with the common clinical laboratory observation of latent fibrin formation in “serum” separated from blood before fibrinogen is fully converted to fibrin. It was concluded that the thrombin-binding anticoagulation model was a reasonable simulation of the situation in which an initial bolus of either exogenous or endogenous thrombin is rapidly partitioned between fibrinogen-bound and ligand-bound forms with little or no additional free thrombin created over time. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 92-103, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 132-138 
    ISSN: 0021-9304
    Keywords: immature cartilage ; solute diffusion ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The diffusive properties of immature bovine articular cartilage were determined using two different-sized, uncharged solutes (glucose 180 Da, and dextran 10k Da). Radioactively tagged glucose and dextran were diffused into the cartilage for transport times of 5, 15, and 60 min, and the diffusion and partition coefficients were calculated by fitting the experimental data to a one-dimensional diffusion model. The diffusion and partition coefficients for the two solutes averaged 6.08 ± 2.19 and 5.09 ± 2.51 (×10-6 cm2/s) and 0.712 ± 0.149 and 0.615 ± 0.120, respectively. Both coefficients were significantly greater for glucose compared to the larger dextran. While no statistical differences could be found in the diffusive properties of these solutes in immature cartilage compared to their diffusive properties in mature cartilage, there was some evidence that the larger dextran solute might diffuse faster in the earlier time periods. Finally, the bulk fluid contents between the two types of cartilage were not different even though the immature tissue was significantly thicker (1.6 times) than the mature tissue. Our results indicate that the solute diffusion properties of articular cartilage, at least with respect to uncharged solutes, do not change during skeletal maturation. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 132-138, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 153-163 
    ISSN: 0021-9304
    Keywords: PEO ; electron beam irradiation ; polymer surface modification ; biocompatibility ; XPS ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A new method was developed for binding poly(ethylene oxide) (PEO) to polymer surfaces that involves the use of electron beam irradiation in two steps. In the first, methacrylic acid was grafted and polymerized to a polymer surface, changing it from hydrophobic to hydrophilic. Exposure of this surface to aqueous PEO solutions resulted in strong hydrogen bonding of the PEO, which was covalently grafted in a second radiation step. The PEO grafts were stable; they could not be removed with extensive washing with water, soaking in basic solution, or gentle mechanical scraping. Both monolayers and multilayers of PEO were formed. The density of the monolayers were found to have little dependence on the molecular weight or concentration of the PEO solution; multilayers could be controlled by varying the viscosity of the PEO solution and the method of application. The PEO-grafted monolayers were tested for their ability to prevent protein adsorption of cytochrome-c, albumin, and fibronectin. Monolayers of star PEO were the most effective, at best showing a 60% decrease in adsorption from untreated controls. One million molecular weight linear PEO monolayers were almost as effective as star monolayers, and 35,000 g/mol linear PEO was bound too closely to the surface, owing to its small size, to have much impact in preventing protein adsorption. The reason for the continued protein adsorption was believed to be due to a close grafting of the PEO to the surface, as well as the grafted methacrylic acid chains being long enough to extend through the PEO monolayer, thus being accessible on the surface. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 153-163, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 187-194 
    ISSN: 0021-9304
    Keywords: skin substitute ; hyaluronic acid derivatives ; integrins ; extracellular matrix ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Coverage of large, full-thickness burns presents a challenge for the surgeon due to the lack of availability of the patient's own skin. Currently, tissue engineering offers the possibility of performing a suitable therapeutic wound coverage after early burn excision by using cultured keratinocyte sheets supported by a dermal layer. The aim of this study was to develop and characterize a skin substitute composed of both epidermal and dermal elements. For this purpose we grew keratinocytes and fibroblasts separately for 15 days within two different types of biomaterials. Cells then were co-cultured for an additional period of 15 days, after which samples were taken and processed with either classic or immunohistochemical stainings. Results showed that (1) human fibroblasts and keratinocytes can be cultured on hyaluronic acid-derived biomaterials and that (2) the pattern of expression of particular dermal-epidermal molecules is similar to that found in normal skin. The data from this study suggest that our skin equivalent might be useful in the treatment of both burns and chronic wounds. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 187-194, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 224-232 
    ISSN: 0021-9304
    Keywords: chemical aging of UDMA ; enthalpy changes of UDMA ; microcalorimetry measurements ; filler effects in composites on enthalpy changes ; silane effects in composites on enthalpy changes ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The isothermal enthalpy changes with time of a dental composite were examined by microcalorimetry to isolate the effects of different filler concentrations and curing times on chemical aging of these composites. Urethane dimethacrylate (UDMA) monomer, zirconia-silica (ZS) powder, and 3-methacryloxypropyltrimethoxysilane (MAPM) were used as organic and inorganic matrices, and a coupling agent, respectively. The composite was mixed in different ratios and cured by visible light. The enthalpy changes with time for 0, 15, 45, 75% ZS-filled UDMA and 75% MAPM-silanated ZS-filled UDMA cured for 13, 30, 90, 150, and 300 s were measured at 37.0°, 57.0°, and 65.5°C until equilibrium. Increased curing time and filler concentration caused the excesss enthalpy changes (dH) and their rate of change (dH/dt) to increase with annealing time and apparent equilibrium was reached faster. In addition, dH showed nonlinear dependence with the increase in filler concentration by showing a maxima for samples containing 25 wt % filler. Further, filler silanation caused dH/dt to increase and required shorter times to reach apparent equilibrium. dH also reached a minimum when samples contained silanated filler, compared to composites containing unsilanated filler. It was concluded that the shorter curing time caused the occurrence of spontaneous densification, which facilitated continual resin curing; and longer curing time caused higher crosslinking of the organic phase. Moderate concentration of inorganic phase restricts the molecular motion of the surface layer of polymer onto filler particles, and the polymer is regarded as highly crosslinked, while a higher filler concentration forms aggregates that are covered by the polymer which causes a decrease in the molecular packing of the resin, and is reflected as low enthalpy values. Finally, silanation of the filler showed a highly endothermic reaction that is probably due to breaking and forming of bonds at the interface between the organic and the inorganic phases in the composites. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 224-232, 1998
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    Journal of Biomedical Materials Research 40 (1998), S. 264-274 
    ISSN: 0021-9304
    Keywords: biocompatible ; neuron growth ; plasma deposition ; ultrathin films ; extracellular matrix ; regeneration ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A method is described for depositing onto medical instruments highly biocompatible and bioactive surface coatings that can promote and stabilize cell attachment. The coatings were made by first depositing thin films of materials, such as diamond-like carbon, or metals, including tantalum, tungsten, platinum, gold, iridium, palladium, and brass. These surfaces were further altered to either promote or inhibit cell growth and spreading by an additional overcoat of biological materials, including the extracellular matrix proteins, laminin, fibronectin, and collagen IV. The deposition technique used a metal or carbon plasma, and the important properties of film adhesion, hardness, density, and smoothness are tailored by control of the ion bombardment energy. The films are translucent enough to permit high resolution light microscopy for rapid and detailed examination of tissue response. These bioactive substrates have been tested on primary central nervous system neurons, and the growth response is excellent. Equally successful have been our attempts to anchor neurons, without associated proliferation of non-neuronal cells, using coatings of poly-d-lysine. The method and the materials could have important ramifications in a number of areas of research and biotechnology, for example for chronic implantation of microelectrode arrays in the cerebral cortex for neuroprosthetic and neural monitoring application and for research on the human central nervous system. Possible applications in non-neuronal fields, such as for coronary artery stents and pacemaker electrodes, also are discussed. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 264-274, 1998.
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    Journal of Biomedical Materials Research 40 (1998), S. 301-306 
    ISSN: 0021-9304
    Keywords: biocompatibility ; biomaterials ; human bone marrow cell culture ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A cell culture system for biocompatibility testing of hip implant materials is described. Human bone marrow cells have been chosen because these cells are in direct contact with the biomaterial after implantation in situ. The sensitivity of this method is evaluated for materials which are already being used as implants in humans and animal, e.g., hydroxyapatite (HA) ceramic, pure titanium, and ultra-high-molecular-weight polyethylene (UHMWPE). As indicative parameters of biocompatibility primary cell adherence, cell number, cell proliferation, production of extracellular matrix, cell vitality, and cell differentiation are described. After 2 weeks in culture, obvious differences between the biomaterials with respect to the indicative parameters could be observed. Cell numbers were greatest on the HA specimens. In the case of titanium alloys, we observed a decreased number of cells. The production of extracellular matrix was high for the HA ceramics but reduced for titanium specimens. The polymers allowed only a few adherent cells and showed no signs of extracellular matrix production. The results can be correlated astonishingly well to animal experiments and clinical experiences. Therefore, we suggest that this cell culture system seems to be a useful tool for biocompatibility testing of bone implantation materials. It also helps reduce animal experiments. With the help of flow cytophotometry, we analyzed the influence of biomaterials on large numbers of cells with respect to differentiation. There were similar populations of T cells and monocytes on all specimens tested. Extended B-cell and granulocyte populations, however, were observed with titanium and UHMWPE. Most osteocalcin-containing cells adhered to the HA ceramics. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 301-306, 1998.
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  • 56
    ISSN: 0021-9304
    Keywords: biphasic calcium phosphate ceramic ; monocyte ; lipopolysaccharides ; polymyxin B ; cell degradation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Numerous cell types, such as monocytes and osteoclasts, are involved in calcified matrix degradation. In this context, calcium-phosphate ceramics present similar degradation processes in vivo and in vitro to those found in a natural calcified substrate. As the monocyte/macrophage lineage is among the first cells to appear in ceramic implantation sites, it is a key protagonist in inflammatory reaction and biodegradation mechanisms. This study investigated the ability of human monocytes/macrophages activated by various agents [lipopolysaccharides (LPS), polymyxin B (PMB)] to degrade biphasic calcium-phosphate ceramics. PMB sulfate is a bacteriostatic antibiotic that modulates LPS-induced cell activities in vivo and in vitro. Degradation pits (about 10 μm) produced on the pellet surface by these monocytes were discrete, with well defined margins. LPS increased the degradation of calcium-phosphate ceramic (number of lacunae, mean pellet surface area degraded) in a dose-dependent manner whereas polymyxin B downmodulated it significantly. The addition of 2 μg/mL of polymyxin B reduced the number of degradation lacunae and the extent of degraded surface area induced by 0.1 μg/mL LPS by 87% and 64%, respectively. Thus this cell culture system can be very useful in the study of cellular degradation of biomaterials and of the influence of therapeutic agents that may modulate these cell activities. © 1998 John Wiley & Sons, Inc. J. Biomed Mater Res, 40, 336-340, 1998
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  • 57
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    Journal of Biomedical Materials Research 40 (1998), S. 365-370 
    ISSN: 0021-9304
    Keywords: protein adsorption ; bacterial adhesion ; α-1-microglobulin ; Ps. aeruginosa ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Urine proteins in the molecular weight range of 9-137 kDa deposit to an equal extent from pooled human urine onto glass (12.7 ± 1.9 μg/cm) and polystyrene (11.8 ± 1.8 μg/cm). Selective desorption of the proteins was achieved by washing with water or water/isopropanol mixtures. Irrespective of the washing process, proteins of molecular weight greater than 90 kDa remained associated with both surfaces while water washings alone removed most low molecular weight material. A 29 kDa protein, α-1-microglobulin, was removed from glass by water washing but required a 30% (v/v) isopropanol wash to desorb from polystyrene, implying attachment via hydrophobic bonding. The adhesion to polystyrene surfaces of Pseudomonas aeruginosa B4, a clinical isolate from a urinary tract infection (UTI), was strongly associated with the presence of α-1-microglobulin, which may be acting as a mediator of bacterial adhesion. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 365-370, 1998.
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  • 58
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    Journal of Biomedical Materials Research 41 (1998), S. 154-161 
    ISSN: 0021-9304
    Keywords: nickel-titanium ; biocompatibility ; genotoxicity ; immunogold labeling ; electron microscopy ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Shape memory nickel-titanium (NiTi) alloys are potential candidates for biomedical applications. However, their equiatomic composition (50 wt% Ni) is controversial, and concerns have been raised about their biocompatibility level because of the carcinogenicity potential. The relative in vitro genotoxicity of NiTi therefore was evaluated and compared to commercially pure titanium (cpTi), 316L stainless steel (SS 316L), and positive and negative controls. To do so, human peripheral blood lymphocytes were cultured in semiphysiological medium that previously had been exposed to the biomaterials. The electron microscopy in situ end-labeling (EM-ISEL) assay then was performed in order to provide quantification of in vitro chromatin DNA single-stranded breaks (SSBs). Chromosomes and nuclei were harvested and exposed to exonuclease III, which amplifies DNA lesions at 3′ ends of breaks. After random priming, incorporation of biotin-dUTP was labeled by immunogold binding, which then was detected using electron microscopy. Cellular chromatin exposed to the positive control demonstrated a significantly stronger immunogold labeling than when it was exposed to NiTi, cpTi, SS 316L extracts, or the untreated control. Moreover, gold particle counts, whether in the presence of NiTi, cpTi, or the negative control medium, were not statistically different. NiTi genocompatibility therefore presents promising prescreening results towards its biocompatibility approval. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 154-161, 1998.
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  • 59
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    Journal of Biomedical Materials Research 41 (1998), S. 221-226 
    ISSN: 0021-9304
    Keywords: thermogravimetry ; differential thermal analysis ; activation energy ; ovariectomy ; traditional Chinese medicine ; 17β-estradiol ; rat ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Thermal analyses [thermogravimetry (TG) and differential thermal analysis (DTA)], X-ray diffraction, and infrared absorption analysis of bones from ovariectomized rats were carried out. The rats were divided into five groups: sham operated (Sham); ovariectomized (OVX); OVX given traditional Chinese (Kampo) medicine, Unkei-to; OVX given 17β-estradiol; and OVX given the estradiol vehicle, respectively. The activation energy (ΔE), a kinetic parameter from TG data of OVX rats, increased by 57% from that in Sham rats. The administration of Unkei-to and 17β-estradiol to OVX rats clearly restored the ΔE to the levels of Sham rats, while the vehicle for 17β-estradiol had no effect. DTA data from thermal analyses of rats from the Sham, OVX, and OVX given various compounds were almost the same except for OVX rats given 17β-estradiol. The X-ray diffraction pattern and infrared absorption spectrum of bone powders from Sham rats were not different from those of OVX rats or others. These results strongly suggest that a kinetic parameter, ΔE calculated from TG data, may be a useful method for assessing both experimentally induced osteoporosis and drug effects on it. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 221-226, 1998.
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  • 60
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    Journal of Biomedical Materials Research 41 (1998), S. 244-250 
    ISSN: 0021-9304
    Keywords: cartilage repair ; osteochondral graft ; chondrocyte transplantation ; articular cartilage defects ; animal model ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: This study reports the development of a novel osteochondral graft for cartilage repair. A technique of proteoglycan extraction via timed enzymatic digestion with hyaluronidase and trypsin and subsequent processing with a chloroform-methanol solution to remove cellular debris from a fresh-frozen bovine osteochondral sample is a method described to prepare a stable biological carrier of low immunogenicity. Lyophilization of the carrier followed by rehydration in a suspension of lapine chondrocytes produced a chimeric xenograft that succeeded in vivo in enhancing cartilage repair. In a pilot study, full-thickness articular cartilage defects treated with these xenografts demonstrated improved healing compared to untreated defects or defects treated with unseeded grafts at 2, 6, and 12 weeks postimplantation. The xenograft provoked a mild inflammatory response; however this did not impede the repair process. Further investigation of this novel chimeric xenograft eventually may yield a method of cartilage repair superior to current methods of treatment. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 244-250, 1998.
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  • 61
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    Keywords: growth substrates ; laminin ; adhesion peptides ; electrochemical coupling ; cell adhesion ; axonal growth ; surface functionalization ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Interactions between cultured nerve cells and surfaces are of importance for the implantation of biocompatible electrode materials such as glassy carbon (GC). Since implants serve as recording sensors in prosthetic neuroscience, we investigated whether coating electrodes with certain laminin derivatives containing the peptide sequences SIKVAV, CDPGYIGSR, PDSGR, YFQRYLI, and RNIAEIIKDA influences neuronal adhesion and neurite outgrowth in vitro. The coating of GC was performed by electrochemical polymerization and, for comparison, by adsorption or covalent coupling. Electrochemical polymerization is suitable for the coupling of peptides to GC, as shown by amino acid analysis and sequencing. Embryonic chicken retinal ganglion cells and brain cells (days E7 or E17) were used for both attachment and growth studies. Surfaces made by electrochemical polymerization of peptides were more efficient than those made by adsorption or covalent coupling of peptides. Synthetic cyclic peptide derivatives of CDPGYIGSR and 18-mer SIKVAV were found to be more efficient than the linear peptides. Competitive effects that resulted in a decreased cell attachment could be found upon application of soluble peptides. Nevertheless, irrespective of the method of coating, peptides were less efficient compared with the whole laminin molecule, as expected from its multiple adhesion sites. When small GC pins were implanted into the brain of E17 chicken after coating with the 18-mer SIKVAV peptide, nerve cell attachment was observed in vivo. The results suggest that chronically implantable materials may exert a higher neurocompatibility when coated with synthetic peptides. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 278-288, 1998.
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  • 62
    ISSN: 0021-9304
    Keywords: bovine platelets ; platelet activation ; flow cytometry ; biocompatibility assays ; ventricular-assist devices ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Cardiovascular device development often relies upon large-animal models to assess blood biocompatibility prior to initiating clinical trials. Unfortunately, the amount of information gleaned from such trials is limited by simple assays that do not take full advantage of immuno-technological advances that increasingly are applied in clinical studies. Thus we have developed and tested new flow cytometric techniques for measuring circulating activated bovine platelets and platelet microaggregates. Monoclonal antibodies (MAbs) raised against both activated and quiescent bovine platelets were incubated with control and PMA- or ADP-stimulated whole blood. Selected MAbs detected activated bovine platelets and platelet microaggregates in vitro with flow cytometry. Five calves implanted with one of two designs of nonpulsatile ventricular-assist devices (VADs) were followed with these assays prior to and during VAD implantation. Circulating activated bovine platelets and microaggregates increased after implantation in all animals and, alternatively, remained elevated or returned toward preimplant levels. Platelet activation percentages as detected temporally by three MAbs were correlated with one another, and platelet activation was correlated with microaggregate formation. In summary, these new methods for the sensitive measurement of circulating activated bovine platelets and microaggregates may provide valuable information for the development and assessment of future cardiovascular device designs. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 312-321, 1998.
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  • 63
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    Journal of Biomedical Materials Research 41 (1998), S. 192-201 
    ISSN: 0021-9304
    Keywords: polyurethane ; dehydroepiandrosterone ; biocompatibility ; biostability ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Poly(etherurethane urea) (PEUU) elastomers, with their broad range of mechanical properties and high biocompatibility, are used clinically for medical applications. However, the possibility exists for the ether soft segment of PEUU to degrade in long-term uses. To retard degradation, antioxidants that scavenge reactive oxygen intermediates are added. In this study, we incorporated dehydroepiandrosterone (DHEA), which functions by the alternate mechanism of modulating or down-regulating adherent macrophage activity, to retard the biodegradation of PEUUs. Biocompatibility of PEUU samples containing 1% DHEA, 5% DHEA, and 5% vitamin E (α-tocopherol) by weight were studied in vivo and in vitro. The biocompatibility was initially evaluated by examination of the inflammatory cellular exudate. Compared to PEUU without additives and PEUU with 5% vitamin E, the addition of 5% DHEA to PEUU caused a decrease in the total leukocyte exudate concentration at 4 days. The addition of 5% DHEA also caused lower macrophage adhesion and FBGC formation compared to the other materials at 7 days. Despite these short-term effects, the biocompatibility at later time points (14, 21, and 70 days) was similar for all materials. Transmission infrared analysis of the materials revealed that more than 70% of the DHEA had leached out of the samples by 3 days implantation. Furthermore, through attenuated total reflectance Fourier transform analysis and scanning electron microscopy, it was determined that unlike vitamin E, DHEA did not enhance long-term PEUU biostability. The effect of DHEA on inflammatory cell activity appeared to be dose dependent, with improved biocompatibility in vivo for higher loading levels of DHEA, but the overall effect was limited owing to the rapid diffusion of the water-soluble DHEA from the PEUU. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 192-201, 1998.
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    Journal of Biomedical Materials Research 41 (1998), S. 227-236 
    ISSN: 0021-9304
    Keywords: commercially pure titanium ; Ti6Al4V ; calcium phosphate ; chemical treatment ; surface modification ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A two-step chemical treatment has been developed in our group to prepare commercially pure titanium (cpTi) surfaces that will allow calcium phosphate (Ca-P) precipitation during immersion in a supersaturated calcification solution (SCS) with ion concentrations of [Ca2+] = 3.10 mM and [HPO42-] = 1.86 mM. It was observed that a precalcification (Pre-Ca) procedure prior to immersion could significantly accelerate the Ca-P deposition process. In this work, the bioactivity of chemically treated cpTi and Ti6Al4V was further verified by applying commercially available Hanks' balanced salt solution (HBSS), an SCS with very low ion concentrations of [Ca2+] = 1.26 mM and [HPO42-] = 0.779 mM, as the immersion solution. It was found that a uniform and very dense apatite coating containing magnesium impurities was formed if the Pre-Ca procedure was performed before immersion, as compared with the loose Ca-P layer obtained from the abovementioned high concentration of SCS. The formation of a microporous titanium dioxide thin surface layer on cpTi or Ti6Al4V by the two-step chemical treatment could be the main reason for the induction of apatite nucleation and growth from HBSS. Variations of pH values, Ca and P concentrations, and immersion time in HBSS were investigated to reveal the detailed process of Ca-P deposition. The described treatments provide a simple chemical method to prepare Ca-P coatings on both cpTi and Ti6Al4V. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 227-236, 1998.
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  • 65
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    Keywords: polyelectrolyte complex ; human periodontal ligament fibroblast ; morphology ; proliferation ; differentiation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Human periodontal ligament fibroblast (HPLF) cultured on tissue culture dishes (TCD), irrespective of the presence of serum, showed only a spreading form. In contrast, using polyelectrolyte complex (PEC) as a matrix, HPLF showed spreading, round, and aggregate forms. Cells of the inner part of the aggregate contacted with each other to form a three-dimensional structure, and this condition corresponded to typical tissues in vivo. These seemed to be related to the interrelation between growth and morphology; that is, the HPLF of the spreading form was considered to belong to a proliferation phase, and the HPLF of the round and aggregate forms, with a little growth, seemed to belong to a functional phase of the cell cycle, indicating that PEC is able to control such cell functions as proliferation, morphology, and differentiation. The cell aggregate was observed only on PEC with carboxymethyl residues and was stained by alizarin red (AR), which suggested mineralization. The spreading cells on PEC containing sulfate residues were not stained by AR. Therefore, it was found that there was a certain relationship between cell growth and morphology, and that PEC affected the cell cycle and promoted proliferation and differentiation of HPLF. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 257-269, 1998.
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  • 66
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    Journal of Biomedical Materials Research 41 (1998), S. 296-303 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Two implant types of hydroxyapatite (HA) currently are available for dental implants: dense HA-cemented titanium (Ti) and HA-coated. It has been shown in previous reports that there are differences in the chemical and mechanical stabilities between the dense HA and HA coated. The differences are thought to be due to structural differences between the two ceramic types. The aim of this study was to investigate the differences in microstructural characteristics of currently available dense HA and HA coated implants before implantation and at periods of 3 weeks and 10 months after implantation in canine bone. X-ray diffractometry, infrared analysis, transmission electron microscopy, and energy dispersive X-ray analysis were used. The dense HA is composed of crystal grains, with a well crystallized structure of HA, closely bound to each other and approximately 0.4∼0.6 μm in size. Implantation did not change the original sintered structure of the dense HA. The HA coating was composed of an amorphous phase with a Ca/P ratio of 1.46 and a crystal phase consisting of oxyhydroxyapatite, tricalcium phosphate, tetracalcium phosphate, and CaO, with a Ca/P ratio of 1.57. In the amorphous phase, compared to other portions in the amorphous phase, there were some layers with lower atomic density and with no significant difference in Ca/P ratio. After implantation, the crystallization of super fine crystals of approximately 4∼5 nm in thickness occurred in the amorphous phase, and with time it progressed and spread from the surface to the deeper portion of the HA coating. A Ca/P ratio of 1.58 in the crystallized portion was close to the ratio (1.60) in the dense HA, suggesting that the super fine crystals were HA. This crystallization cannot significantly decrease the solubility of the amorphous phase portion and poses risks of stress accumulation within the coating and a decrease of binding strength between the HA coating and the substrate. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 296-303, 1998.
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    Journal of Biomedical Materials Research 41 (1998), S. 333-340 
    ISSN: 0021-9304
    Keywords: inflammatory responses ; complement activation ; gold surfaces ; thiols ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Biomaterial-mediated complement activation repeatedly has been invoked as a trigger of phagocyte reactions and inflammation. However, a direct correlation between complement activation and inflammatory responses to biomaterial surfaces has yet to be established. Using an animal implantation model and gold surfaces bearing various thiol-linked functionalities, we investigated the potency of different surface groups in prompting complement activation in vitro and surface-mediated accumulation of inflammatory cells in vivo. Among the surfaces tested, mercaptoglycerol- and mercaptoethanol-bearing surfaces engendered the strongest inflammatory responses, as reflected by the accumulation of large numbers of adherent neutrophils and monocytes/macrophages. In contrast, L-cysteine-coated surfaces caused only minor inflammatory responses, and both glutathione-modified and untreated gold implants attracted minimal numbers of inflammatory cells. The accumulation of inflammatory cells on mercaptoglycerol surfaces appears to arise from surface-mediated complement activation because complement-depleted animals failed to exhibit inflammatory responses to mercaptoglycerol-modified implants. Furthermore, there is a close relationship between surface-mediated complement activation (as measured by in vitro iC3b/C5b-9 generation and C3 deposition) and in vivo inflammatory responses. At least in this animal model and with these model surfaces, our results indicate that surface-mediated complement activation can be responsible for the subsequent accumulation of inflammatory cells on implant surfaces. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 333-340, 1998.
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    Journal of Biomedical Materials Research 41 (1998), S. 349-358 
    ISSN: 0021-9304
    Keywords: contact angles ; adherence to ρ-xylene ; zeta potentials and surface charges of bacteria ; sutures ; low-temperature plasma treatment ; bacterial attachment ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In this study, five different bacteria with their different strains were isolated and characterized. Contact angles were measured by a captive-bubble technique. Surface-free energies were calculated from the contact angles. Hydrophobicities also were evaluated by ρ-xylene adhesion. The zeta potentials and surface charges of the bacteria were obtained. The contact angles of the gram-positive bacteria and gram-negative bacteria were within the range of 48°-69° and 43.5°-55°, respectively, while corresponding surface-free energies were in the limits of 45.4-51.6 erg/cm-2 and 51.7-61.8 erg/cm-2, respectively. The ρ-xylene adhesions were parallel to hydrophobicities defined by contact angles, and 32.2-80.3% and 2.3-36.6% for the gram-positive bacteria and gram-negative bacteria, respectively. The zeta potentials for these bacteria were from -650.2 to +17.5 mV and from -159.6 to -6.0 mV, respectively. Most of the bacteria were negatively charged, except the CNS-2 and CPS-1 strains. In the second part of the study, attachment of these bacteria to Vicryl® sutures and their DMAEMA and AAc plasma-treated forms were investigated. Hydrophobic bacteria attached more to hydrophobic Vicryl® sutures. Both plasma treatments caused significant drops in bacterial attachment in most cases. Effects of AAc plasma treatment were more pronounced. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 349-358, 1998.
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    Journal of Biomedical Materials Research 41 (1998), S. 104-110 
    ISSN: 0021-9304
    Keywords: bone morphogenetic protein ; osteoblasts ; microspheres ; poly(d,l lactide-co-glycolide) ; cellular responses ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Porous 50:50 poly(d,l lactide-co-glycolide) microspheres containing varying amounts of “free” recombinant human bone morphogenetic protein-2 (rhBMP-2) were evaluated for their ability to induce/enhance expression of osteoblastic characteristics by pluripotent mesenchymal cells in vitro. “Free” protein (Fp) is defined as protein present on the surface and within the porous matrix of the microspheres. Four preparations of bioerodible particles (BEP) were used: blank - without rhBMP-2; low Fp - 24 μg of free rhBMP-2 per g of particles; medium Fp - 403 μg/g; and high Fp - 884 μg/g. C3H10T1/2 cells (C3H) and bone marrow stromal cells (BMC) were cultured with 1 mg of BEP for up to 4 weeks, and cell growth and expression of osteogenic responses were determined weekly. For both cell types, control cultures (neither BEP nor rhBMP-2) and cultures with blank BEP exhibited no or minimal osteoblastic characteristics. Compared to control and blank BEP cultures, C3H cells responded to particles having medium and high amounts of free rhBMP-2 with increased cell growth and alkaline phosphatase activity, but osteocalcin secretion and mineralization were not markedly influenced. Low Fp BEP enhanced only the alkaline phosphatase activity of C3H cells. In contrast, although growth was not affected, rhBMP-2-loaded BEP increased alkaline phosphatase activity, osteocalcin secretion, and mineralization in BMC cultures in a dose-dependent manner (i.e., blank 〈 low 〈 medium 〈 high Fp). © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 104-110, 1998.
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  • 70
    ISSN: 0021-9304
    Keywords: biomaterials ; polyurethanes ; infection ; infection resistance ; surface modification ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Tissue reactions to implantable pacemaker leads were investigated in an early infection model in rabbits. Both standard leads and surface-modified leads were used. The surface modification technique was applied to achieve controlled release of the antibiotic gentamicin. The insulating polyurethane tubing material of the leads was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. Implantation periods varied from day 4, to week 3½, to week 10. We investigated tissue reactions in the absence of an infectious challenge and also the efficacy of surface-modified leads in preventing infection after challenge with Staphylococcus aureus was evaluated. It was demonstrated that the applied surface modification did not induce adverse effects although during early postimplantation an increase in infiltration of granulocytes and macrophages and wound fluid and fibrin deposition were observed. After bacterial challenge, standard leads were heavily infected at each explantation period, denoted by abscesses, cellular debris, and bacterial colonies. In contrast, little or no infection was observed, either macroscopically or by bacterial cultures, with the surface-modified leads. Microscopy showed little evidence of the bacterial challenge, and that primarily at day 4. It was concluded that the applied surface modification demonstrated enhanced infection resistance and thus represents a sound approach to the battle against infectious complications with biomaterials. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 142-153, 1998.
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    Journal of Biomedical Materials Research 41 (1998), S. 167-170 
    ISSN: 0021-9304
    Keywords: FT-IR ; microspectroscopy ; infrared ; injectable biomaterial ; calcium phosphate ; bone substitute ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Hydroxypropylmethylcellulose (HPMC) of high-viscosity grade is used as a ligand for a bioactive calcium phosphate ceramic (the filler) in a ready-to-use injectable sterilized biomaterial for bone and dental surgery. Application of physico-chemical methods such as XPS, NMR, or Raman spectroscopy encounters difficulties when used to study such a multiphased material. This paper reports on the application of FT-IR microspectroscopy (FT-IRM) for the investigation of inorganic and organic phases of the rough composite and separated phases obtained by mechanical or chemical extraction methods. A comparison of FT-IRM with the conventional KBr pellet method was made and indicates that the macro and micro FT-IR methods are complementary: the former revealed new chemical groups not visualized with the KBr method whereas the latter detected the major compound of the blend. FT-IR microspectroscopy was revealed to be a powerful method of analysis that is complementary to other existing spectroscopic methods. Moreover, it is expected to be a useful tool in the study of biomaterials in biological samples. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 167-170, 1998.
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    Journal of Biomedical Materials Research 42 (1998), S. 45-54 
    ISSN: 0021-9304
    Keywords: nanospheres ; polylactic acid-polyethylene glycol ; protein encapsulation ; protein delivery ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The development of injectable nanoparticulate “stealth” carriers for protein delivery is a major challenge. We have shown the possibility of entrapping human serum albumin (HSA) in polyethylene glycol (PEG)-coated monodisperse biodegradable nanospheres with a mean diameter of about 200 nm, prepared from amphiphilic diblock PEG-polylactic acid (PLA) copolymers, with loadings up to 9% (w/w). Microscopic techniques and surface analysis studies enabled us to prove that the protein was well entrapped and not adsorbed onto the particle surface. Zeta potential and water uptake studies corroborated that part of the PEG chains are located in the nanosphere matrix. Water uptake in the nanospheres was related to their chemical composition, i.e., the respective wt% of PEG and PLA in the matrix, and not on their fabrication procedure. The hydrophilic PEG blocks absorbed up to 130% (w/w) water, whereas PLA absorbed only about 10% (w/w). However, the rate of swelling at the beginning of the process was related to the structure of the matrix, more particularly to the manner in which PEG was disposed at the surface. Furthermore, it was shown that the PEG “brush” at the nanosphere surface drastically reduces HSA adsorption on the PEG-PLA nanospheres compared to the PLA ones. © 1998 John Wiley & Sons, Inc. J. Biomed Mater Res, 42, 45-54, 1998.
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  • 73
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The effectiveness of ethanol pretreatment on preventing calcification of glutaraldehyde-fixed porcine aortic bioprosthetic heart valve (BPHV) cusps was previously demonstrated, and the mechanism of action of ethanol was attributed in part to both lipid removal and a specific collagen conformational change. In the present work, the effect of ethanol pretreatment on BPHV aortic wall calcification was investigated using both rat subdermal and sheep circulatory implants. Ethanol pretreatment significantly inhibited calcification of BPHV aortic wall, but with less than complete inhibition. The maximum inhibition of calcification of BPHV aortic wall was achieved using an 80% ethanol pretreatment; calcium levels were 71.80 ± 8.45 μg/mg with 80% ethanol pretreatment compared to the control calcium level of 129.90 ± 7.24 μg/mg (p = 0.001). Increasing the duration of ethanol exposure did not significantly improve the inhibitory effect of ethanol on aortic wall calcification. In the sheep circulatory implants, ethanol pretreatment partly prevented BPHV aortic wall calcification with a calcium level of 28.02 ± 4.42 μg/mg compared to the control calcium level of 56.35 ± 6.14 μg/mg (p = 0.004). Infrared spectroscopy (ATR-FTIR) studies of ethanol-pretreated BPHV aortic wall (vs. control) demonstrated a significant change in protein structure due to ethanol pretreatment. The water content of the aortic wall tissue and the spin-lattice relaxation times (T1) as assessed by proton nuclear magnetic resonance spectroscopy did not change significantly owing to ethanol pretreatment. The optimum condition of 80% ethanol pretreatment almost completely extracted both phospholipids and cholesterol from the aortic wall; despite this, significant calcification occurred. In conclusion, these results clearly demonstrate that ethanol pretreatment is significantly but only partially effective for inhibition of calcification of BPHV aortic wall and this effect may be due in part to lipid extraction and protein structure changes caused by ethanol. It is hypothesized that ethanol pretreatment may be of benefit for preventing bioprosthetic aortic wall calcification only in synergistic combination with another agent. © 1998 John Wiley & Sons, Inc. J. Biomed Mater Res, 42, 30-37, 1998.
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  • 74
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    Journal of Biomedical Materials Research 42 (1998), S. 96-102 
    ISSN: 0021-9304
    Keywords: coral ; calcite ; cell culture ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The two crystalline forms of CaCO3, aragonite (from natural coral) and calcite (from natural limestone), have been used with success as bone graft substitutes. However, natural coral transformed into calcite by heating has never been tested. The objective of this work was to study the proliferation and alkaline phosphatase, osteonectin, and osteocalcin expression of human bone marrow cells cultured on CaCO3 crystallized both in the aragonite form (natural coral) and in the calcite form (natural coral modified by heating). The methods used to characterize calcite obtained from the coral were volumic porosimetry, scanning electron microscopy (SEM) and X-ray diffraction. Cell colonization of the material was assessed by SEM performed on days 1, 7, 20, and 30 and [3H]thymidine incorporation was performed on days 3, 7, 12, 18, 25, and 32. Phenotypic expression was assessed by using in situ cytochemistry (alkaline phosphatase), immunocytochemistry (osteonectin and osteocalcin), and hybridization (osteocalcin, β-actin, and alkaline phosphatase mRNA). Results showed the transformation of aragonite into calcite after heating, the conservation of macroporosity, and a modification of the surface. Calcite appeared to have a smoother and more uniform surface than aragonite crystals. As for [3H]thymidine there was an increase incorporation from days 3 to 18, a stabilization from days 18 to 25, and a decrease from days 25 to 32. After 20 days of culture, immunological studies using monoclonal antibodies to osteocalcin, osteonectin, cytochemical analysis of alkaline phosphatase activity, and in situ hybridization using osteocalcin, β-actin, and alkaline phosphatase cDNA indicated that the cells had not lost their osteoblastic phenotype. These experiments demonstrate that coral crystallized in the aragonite or calcite form present a similar degree of specific cytocompatibility. © 1998 John Wiley & Sons, Inc. J. Biomed Mater Res, 42, 96-102, 1998.
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  • 75
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    Journal of Biomedical Materials Research 42 (1998), S. 112-116 
    ISSN: 0021-9304
    Keywords: drug delivery system ; occlusive dressing ; antibiotic ; drug-polymer conjugate ; infection ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: An ideal drug delivery system (DDS) releases an appropriate drug at specific locations and times. We tried to create a new antibiotic delivery system that releases gentamicin only when wounds are infected by Pseudomonas aeruginosa (P.A.). Exudate from the dorsal pouch of rats infected with P.A. showed significantly higher hydrolytic activity - thrombin-like activity - toward Boc-Val-Pro-Arg-MCA than exudate from noninfected wounds. We therefore constructed a device for controlled release of an antimicrobial drug triggered by thrombin-like activity. Briefly, gentamicin was bound to a polyvinyl alcohol derivative (PVA) hydrogel through a newly developed peptide linker cleavable by the proteinase, PVA-(linker)-gentamicin. In vitro experiments showed that proteinases from wounds infected with P.A. cleaved the linker and gentamicin was released while the exudate from noninfected wounds had no hydrolytic activity toward the linker. This device shows potential as an occlusive dressing with an effective antibiotic delivery system for treating infected wounds. © 1998 John Wiley & Sons, Inc. J. Biomed Mater Res, 42, 112-116, 1998.
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  • 76
    ISSN: 0021-9304
    Keywords: dentin ; demineralization ; shrinkage ; rehydration ; atomic force microscopy ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Most current dentin bonding procedures use acid etchants to partially demineralize the dentin structure and provide pathways for resin infiltration. This study determined the recession rates of peritubular dentin and intertubular dentin as a function of pH during demineralization in citric acid solutions (0.0005-2.5M) and the effects of dehydration and rehydration on the partially demineralized dentin. Polished dentin disks were prepared with an internal reference layer and were studied at specific intervals for citric acid etching between pH 1 and 3.4 in an atomic force microscope. Peritubular dentin etched rapidly and linearly with time until it could no longer be measured. The intertubular surface began etching at nearly the same rate, but then recession slowed for all concentrations and stabilized after recession of less than 1 μm for all but the pH 1 solution. The decrease in recession was attributed to the limitation of contraction of the demineralized collagen scaffold as long as it remained hydrated. Dehydration following etching resulted in significant collapse of the surface, changes in roughness, and a slight decrease in tubule diameter for samples etched for 30 min. Measurements could not be made of the collapse for low pH samples, because shrinkage stresses disrupted the integrity of the reference layer. On rehydration, the dehydrated surfaces underwent an expansion up to the level seen after etching and tubule diameters returned to the etched values. These results indicate that the collapse of demineralized matrix is almost totally recoverable on rehydration. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 500-507, 1998.
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  • 77
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    Journal of Biomedical Materials Research 42 (1998), S. 278-285 
    ISSN: 0021-9304
    Keywords: apatite ; assay ; biomaterial ; biomimetic ; osteoclast ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: We have investigated the applicability of a simple and inexpensive osteoclastic assay system using bone-like apatite-coated polyethyleneterephthalate (PET) disks. A 1 μm thick apatite layer, uniform and homogeneous bone-mineral-like with no organic components, was made on PET disks using a biomimetic process. As substrates for an osteoclastic assay, these coated disks were compared with dentine as well as with bone-like or heat-treated apatite of various thicknesses on apatite- and wollastonite-containing glass ceramic (A-W GC) disks. The unfractionated bone cells, including osteoclasts, of a neonatal rabbit were seeded onto these substrates. By scanning electron microscopic examination, the resorption lacunae of the thick bone-like apatite clearly showed track-like shapes at various depths, similar to those of dentine although the border between the A-W GC and the apatite was unclear. In contrast, those of heat-treated apatite showed small and shallow shapes with irregular margins, quite different from those of dentine. By reducing the thickness of bone-like apatite to 1 μm as well as using PET as its substrate, the margins of the resorption lacunae became quite clear, and with the use of phase-contrast microscopy during culture, osteoclasts and resorption pits could be precisely observed. The resorbed area, easily measured with the aid of bright-field microscopy and an image analyzer, was found to have increased in a time-dependent manner and at the end of 4 days of culture was not statistically different from that of dentine. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 278-285, 1998.
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  • 78
    ISSN: 0021-9304
    Keywords: RGTA/heparin-like ; collagen ; atherosclerosis ; antifibrosis ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: We developed regenerating agents (RGTAs) corresponding to polysaccharides derived from dextran and containing defined amounts of carboxymethyl (CM), carboxymethyl sulfate (CMS), carboxymethyl benzylamide (CMB), or carboxymethyl benzylamide sulfate (CMBS) groups with varying degrees of substitution. These compounds mimicked some effects of heparin on smooth muscle cell (SMC) proliferation and promoted in vivo tissue remodeling. We demonstrated that only RGTAs containing both CM and sulfate groups decreased SMC proliferation, in correlation with increased sulfation level. This effect was amplified by the presence of benzylamide. Independent of this activity on cell proliferation (i.e., with postconfluent cells), RGTAs modulated collagen biosynthesis by SMCs. On the one hand, CMBS more than CMS RGTAs induced a decrease of collagen III synthesis at the level of mRNA steady state and protein production. On the other hand, CMS to a greater extent than CMBS RGTAs increased both collagen V mRNA and protein production. In addition, only benzylamide-containing RGTAs increased accumulation of collagen I and III in the cell layer. In conclusion, RGTA bioactivities required the presence of CM functions, increased with the sulfation level, and varied with benzylamide substitution. RGTAs that modulate cell proliferation and collagen biosynthesis by differential mechanisms may represent potential antifibrotic agents. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 286-294, 1998.
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  • 79
    ISSN: 0021-9304
    Keywords: sol-gel films ; titania ; silica ; dip coating ; bioactivity ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Different sol-gel-derived titania and titania-silica films were prepared and their properties related to in vitro bioactivity. The films were prepared by depositing the sols on the substrate surface using a dip-coating method. The sols were monitored carefully as a function of time, using rheological techniques and dynamic light scattering. The topography of the films was characterized using atomic force microscopy, and thicknesses and refractive indexes of the films were evaluated by fitting transmittance spectra measured in a wave length region of 370-1100 nm with a spectrophotometer. The in vitro bioactivity tests were performed in simulated body fluid. Surface topography was found to be of great importance with respect to the bioactivity of the studied films. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 295-302, 1998.
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  • 80
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    Journal of Biomedical Materials Research 42 (1998), S. 272-277 
    ISSN: 0021-9304
    Keywords: anodic oxide titanium ; hydrothermal treatment ; SA-treated titanium ; biomaterial ; immunocyte ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: All dental root implants come in contact with the oral epithelium, and many complex factors are found to arise in this region. In order to perform a successful dental root implantation, it is necessary to clarify the interaction of the dental root implant material with the host defense mechanisms involved in the specific and nonspecific immune responses to many antigens in oral bacteria and their components. Recently, focusing on developing the dental root implant, the Nikon Corporation improved the surface characteristics of pure titanium even further by developing a hydroxyapatite (HA) layer formed on an anodic titanium oxide film containing Ca and P via hydrothermal treatment (SA treatment). However, since little is known about the effect of SA-treated pure titanium (HA/Ti) on the defense mechanisms of the oral membrane epithelium, we investigated (1) the in vitro proliferation of murine splenic B lymphocytes on the surface of HA/Ti in the presence of three lipopolysaccharide (LPS) concentrations and (2) interleukin-1α (IL-1α) production by the reaction of human peripheral blood mononuclear cells (PBM cells) on the surface of HA/Ti under the same concentrations. After culture, murine splenic lymphocytes were measured by uptake of 3H-thymidine, and cytokine release (IL-1α) from PBM cells was measured by ELISA. Results showed that HA/Ti had hardly any effect on the LPS-induced proliferation of B lymphocytes and IL-1α production. In vitro investigations of the effects of HA/Ti on the LPS-induced proliferation of murine splenic B lymphocytes and IL-1α from PBM cells might be a useful way of elucidating the defense mechanism between implants and the oral epithelium. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 272-277, 1998.
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  • 81
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    Journal of Biomedical Materials Research 43 (1998), S. 54-61 
    ISSN: 0021-9304
    Keywords: acrylic bone cement ; differential scanning calorimetry ; hydroxyethyl methacrylate ; ethylene glycol dimethacrylate ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The polymerization reaction of standard surgical Simplex®-P radiopaque bone cement was investigated by differential scanning calorimetry to determine the influence of hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) on the polymerization reaction. From the kinetic analysis, the polymerization reaction of the modified acrylic bone cement was found to be approximately a first-order reaction. The reaction rate constants (k) were determined. It was found that the effects of HEMA and EGDMA contents on the rate and the heat of polymerization can be explained by the frequency factor and the activation energy. An increase in HEMA content tends to result in an increase in the values of both frequency factor and activation energy, whereas an increase in EGDMA content tends to induce a decrease in the frequency factor and activation energy. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 54-61, 1998
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  • 82
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    Journal of Biomedical Materials Research 43 (1998), S. 62-68 
    ISSN: 0021-9304
    Keywords: hip prosthesis ; taper ; standardization ; mechanical properties ; ceramic heads ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Standardization of bores and cones for modular hip prosthesis heads has been addressed by both the International Standard Organisation (ISO) and the American Society for Testing and Materials (ASTM) in response to the need to control the conditions of head-trunnion fit that thereby improves implant safety. Standardization of these conditions could help the surgeon avoid fit mismatch, especially during revision surgery. Instituting a system of standardization without taking all critical parameters into consideration, however, could be more dangerous than no system at all. The current article discusses the main taper parameters that directly influence the performance of ceramic head-metallic trunnion assemblies and argue for standardization that integrates all these parameters. Several examples, based on experimental mechanical tests and finite element analysis, are given to support the argument. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 62-68, 1998
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  • 83
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    Journal of Biomedical Materials Research 43 (1998), S. 89-98 
    ISSN: 0021-9304
    Keywords: gelatin ; films ; tissue ; bonding ; argon beam ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Cross-linked gelatin films were bonded to heart muscle and to lung pleura and parenchyma using the electrical discharge of an argon beam radiofrequency coagulator. The bonds were stable in warm saline buffer for minutes to hours. Bonding was thought to partly occur through a mechanical interlock of film and tissue elements. The interdigitation of tissue and film arose during exposure to the argon beam, which denatured protein constituents of both, and created a fluidized state that rapidly coalesced. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 89-98, 1998
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  • 84
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    Journal of Biomedical Materials Research 43 (1998), S. 113-122 
    ISSN: 0021-9304
    Keywords: plasma-sprayed HA coating ; HA coating-metal substrate ; tensile strength ; degradation ; bone bonding ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Tensile strength testing of the interface between bone and a plasma-sprayed hydroxyapatite (HA) coating-Ti-6Al-4V (implant I) and an HA coating-Ti (implant II) was performed. The bone-implant interface and tensile failure mode were evaluated by light microscopy (LM), SEM-energy dispersive X-ray analysis, and backscattered electron imaging. The crystallinity of the HA coating of implant I and implant II was 62 and 40%, respectively. Eleven semidisk implants of each type were inserted in the left tibia of 22 rabbits in each period. After 2, 4, 8, and 16 weeks, the tensile strength of the bone-implant I was 0.86, 1.32, 1.10, and 0.92 MPa, respectively; the value of the bone-implant II was 0.66, 0.92, 0.84, and 1.12 MPa, respectively. No significant difference was found in tensile strength between implant I and implant II, and between the data of different periods. LM and SEM revealed that the two types of coatings behave the same in bone. Failure after the tensile test mainly occurred at the bony tissue at 2 and 4 weeks, inside the HA coating layer at 8 weeks, and at the HA coating-metal substrate interface at 16 weeks. Degradation and delamination of the HA coating continued with time, resulting in the interfacial tensile strength not increasing with time. Thus, we concluded that differences between the two implants, mainly the difference in crystallinity of the HA coating (62 vs. 40%), have no significant influence on bone bonding ability, bone bonding strength, tensile failure mode, and degradation of the coating. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 113-122, 1998
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  • 85
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    Journal of Biomedical Materials Research 42 (1998), S. 321-330 
    ISSN: 0021-9304
    Keywords: titanium ; osteoblast ; oxygen ; corrosion ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Mechanically assisted corrosion processes can greatly increase the oxidation currents generated in passivating alloy systems like Co-Cr and titanium due to oxide film disruption. When oxide films are abraded, repassivation and ionic dissolution both occur at rates that are orders of magnitude higher than undisrupted surfaces. The excess electrons generated by these anodic processes must be consumed in corresponding reduction reactions that include the reduction of oxygen. If large enough, these reduction reactions may locally deplete the concentration of solution-dissolved oxygen and, in turn, affect cell behavior in the vicinity of the implant surface. To date, this hypothesis has not been tested. In the present study, a scanning electrochemical microscope was used to measure oxygen concentration profiles in vitro near a planar titanium electrode polarized to different voltages representative of those attainable by titanium undergoing mechanically assisted corrosion. The potentials investigated ranged from 0 mV to -1000 mV (AgCl). The oxygen concentration as a function of distance from the titanium surface was measured using a platinum-iridium microelectrode and an amperometric technique. Also, preliminary experiments were performed to assess the response of rat calvarial osteoblast-rich cells cultured for 2 h on titanium samples polarized to two different potentials (0 mV and -1000 mV versus AgCl). The results of this study indicate that oxygen concentrations near titanium surfaces are affected by sample potentials out to probe-sample distances as great as 500 μm. Within 2 μm of the surface, oxygen concentrations decreased by 15 to 25% for sample potentials between -100 and -500 mV. At potentials more negative than -600 mV, the oxygen concentration dropped rapidly to near zero by -900 mV. The cell experiments showed a statistically significant difference in the amount of cell spreading, as measured by projected cell area, between the two groups (p 〈 0.03), with the cells cultured at -1000 mV undergoing much less spreading. This implies that -1000 mV inhibits normal cell behavior at the titanium surface and that this is most likely due, at least in part, to a diminished oxygen supply. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 321-330, 1998.
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    Journal of Biomedical Materials Research 42 (1998), S. 340-340 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
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  • 87
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    Journal of Biomedical Materials Research 42 (1998) 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
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  • 88
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    Journal of Biomedical Materials Research 42 (1998), S. 331-338 
    ISSN: 0021-9304
    Keywords: paclitaxel ; nanosphere ; restenosis ; smooth muscle cell ; endocytosis ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Available data suggest that drugs should be delivered to a vascular lesion at a high concentration over an extended period of time to control vascular smooth muscle cell (VSMC) proliferation. This study was undertaken to formulate a paclitaxel, an antimicrotubule agent, into a biodegradable poly (ethylene oxide)-poly(lactide/glycolide) (PEO-PLGA) nanosphere as a sustained drug delivery system and to study its effects on VSMC in culture. The paclitaxel-loaded nanospheres (PT/NS), prepared by an emulsion-solvent evaporation method, had an average diameter of ∼150 nm and showed a sustained release profile over 4 weeks. The PT/NS exhibited antiproliferative effects comparable to those observed with free paclitaxel. The cellular internalization of nanospheres was visualized using confocal fluorescence microscopy, and from a flow cytometry study the progressive cellular uptake profile, uptake inhibition at low temperature, and saturation uptake kinetics (concentration dependency) were observed. These suggest that (adsorptive) pinocytosis is a major uptake mechanism of the nanospheres. The sustained drug release profile and cellular internalization results suggest that nanospheres loaded with paclitaxel may potentially be used as an endocytizable, local sustained drug delivery system for the prevention of restenosis. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 331-338, 1998.
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    Journal of Biomedical Materials Research 42 (1998), S. 341-346 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
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  • 90
    ISSN: 0021-9304
    Keywords: tissue reactions ; bone sites ; histomorphometry ; bioceramics ; porosity ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In order to understand the influence of the implantation site on bone biomaterial evaluation, we implanted cylinders of HA and β-TCP ceramics in the femoral diaphysis and condyle of rabbits. After 3, 8, 12, and 24 weeks of implantation, histological investigation and histomorphometry were performed on undecalcified samples. Our results show that spontaneous bone healing in the empty cavities is significantly different (p 〈 0.05) between cortical (SBH 〉 80%) and cancellous bone sites (SBH 〈 31%) and that no new bone is formed in marrow tissue. For both porous ceramics, the highest osteogenesis was obtained in the cortical site. Osteogenesis was intermediate in the cancellous site and weak in the medullar site. The material biodegradation was the strongest in the medullar site and higher in the cancellous site than in the cortical site. Both activities were better in the β-TCP than in the HA (p 〉 0.05). The marrow tissue presents a foreign-body reaction more reliable, sensitive, and durable than other bone tissues. Therefore, the cancellous bone site is a good site for evaluation of the biofunctionality of biomaterials because of the equilibrium of the osteogenesis and the biodegradation activities, but marrow tissue seems to be better for testing material biocompatibility in vivo. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 357-367, 1998.
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  • 91
    ISSN: 0021-9304
    Keywords: cartilage transplantation ; perfusion culture ; tissue engineering ; polymer scaffolds ; matrix synthesis ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: New cell culture techniques raise the possibility of creating cartilage in vitro with the help of tissue engineering. In this study, we compared two resorbable nonwoven cell scaffolds, a polyglycolic acid/poly-L-lactic acid (PGA/PLLA) (90/10) copolymer (Ethisorb) and pure PLLA (V 7-2), with different degradation characteristics in their aptitude for cartilage reconstruction. Chondrocytes were isolated enzymatically from human septal cartilage. The single cells were resuspended in agarose and transferred into the polymer scaffolds to create mechanical stability and retain the chondrocyte-specific phenotype. The cell-polymer constructs were then kept in perfusion culture for 1 week prior to subcutaneous transplantation into thymusaplastic nude mice. After 6, 12, and 24 weeks, the specimens were explanted and analyzed histochemically on the presence of collagen (azan staining), proteoglycans (Alcian blue staining), and calcification areas (von Kossa staining). Furthermore, different collagen types (collagen type I, which is found in most tissues, but not in hyaline cartilage matrix; and collagen type II, which is cartilage specific) were differentiated immunohistochemically by the indirect immunoperoxidase technique. Vascular ingrowth was investigated by a factor VIII antibody, which is a endothelial marker. Quantification of several matrix components was performed using the software Photoshop. Significant differences were found between both nonwoven structures concerning matrix synthesis and matrix quality as well as vascular ingrowth. Ethisorb, with a degradation time of approximately 3 weeks in vitro, showed no significant differences from normal human septal cartilage in the amount of collagen types I and II 24 weeks after transplantation. Thin fibrous tissue layers containing blood vessels encapsulated the transplants. V 7-2 constructs, which did not show strong signs of degradation even 24 weeks after transplantation, contained remarkably smaller amounts of cartilage-specific matrix components. At the same time, there was vascular ingrowth even in central parts of the transplants. In conclusion, polymer scaffolds with a short degradation time are suitable materials for the development of cartilage matrix products, while longer stability seems to inhibit matrix synthesis. Thus, in vitro engineering of human cartilage can result in a cartilage-like tissue when appropriate nonwovens are used. Therefore, this method could be the ideal cartilage replacement method without the risk of infection and with the possibility of reconstructing large defects with different configurations. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 347-356, 1998.
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  • 92
    ISSN: 0021-9304
    Keywords: charged beads ; soft tissue repair ; degradable ; wound healing ; crosslinked diethylaminoethanol dextran ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Previous work in the area of vulnerary agents is extensive. One material of focus has been positively charged ion exchange beads, which have been shown to promote a variety of wound-healing responses in several models. The goal of this work was to improve upon the clinical utility of positively charged dextran beads by creating a biodegradable version that maintains the material's inherent efficacy. A chemical method consisting of a sodium periodate oxidation was used to create a degradable diethylaminoethanol crosslinked dextran bead. The ability of this process to create a degradable bead was verified in vitro and in vivo. Furthermore, efficacy was shown in a rat linear incision model for a variety of beads exhibiting different degradation rates. The results show that efficacy is maintained by a degradable bead, but there is a diminution of the magnitude of the response as the mass loss rate is increased. Efficacy also was investigated for a moderate but completely degrading bead material over time and dose. Wound breaking strength was evaluated at days 7, 10, 14, 21, and 28 for degradable beads at doses of 10 mg/mL and 50 mg/mL. Although little difference in efficacy was noted for the increased dose, statistically significant increases over control were seen at days 7, 10, and 14 for the 10 mg/mL dose and at days 10 and 14 for the 50 mg/mL dose. At days 21 and 28 there were no differences between treated and control wounds. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 376-386, 1998.
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    Journal of Biomedical Materials Research 42 (1998), S. 368-375 
    ISSN: 0021-9304
    Keywords: particulate biphasic calcium phosphate ; long-term bone implantation ; inflammatory reaction ; histomorphometry ; material degradation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Biphasic calcium phosphate particles (BCP), alone or combined with a cellulosic ether vehicle in an injectable composite material (COMP), were implanted in femurs of rabbits. The long-term follow-up (up to 78 weeks) indicated: (1) BCP and COMP induced a foreign-body inflammatory reaction but without fibrous encapsulation. Phagocytosis was mediated by mononucleated macrophages (MC) and giant multinucleated cells (GMNC). Phagocytosis was stronger with COMP and required the recruitment of GMNC while it primarily involved MC in the case of BCP. (2) There appeared to be no significant difference between the bone ingrowth in the defects packed with BCP (dBCP) and in those filled with COMP (dCOMP). Bone reconstruction mostly was achieved after 4 weeks in dBCP but took more time to reach the center of dCOMP. High bone remodeling was observed at the last evaluation times, especially in the case of COMP. (3) Degradation of the materials occurred mainly during the first 4 weeks and was more severe for COMP, which probably was related to the smaller granulometry of its mineral phase. Cell-mediated degradation went on for the 78 weeks and followed two processes: phagocytosis and/or extracellular dissolution of the calcium phosphate particles. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 368-375, 1998.
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  • 94
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    Journal of Biomedical Materials Research 42 (1998), S. 387-395 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; hydrothermal-electrochemical ; deposition ; titanium ; coating ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Hydroxyapatite crystals were formed on a titanium electrode using the hydrothermal-electrochemical method in an autoclave with two electrodes. The electrolyte dissolving NaCl, K2HPO4, CaCl2 · 2H2O, trishydroxyaminomethane, and hydrochloric acid was maintained at 80°-200°C. After loading of a constant current at 12.5 mA/cm2 for 1 h, the deposited amounts were measured through the weight gain of the electrode. The deposits were characterized by X-ray diffractometry, Fourier transform infrared spectroscopy, field emission-type scanning electron microscopy, field emission-type transmission electron microscopy, and energy dispersive X-ray spectroscopy. The deposited amount increased with electrolyte temperatures up to 150°C and slightly decreased above that temperature. The deposits were identified as hydroxyapatite crystal rods grown along the c axis and perpendicular to the substrate. The crystallinity of the deposited hydroxyapatite increased continuously with the electrolyte temperature and closed to stoichiometric hydroxyapatite. At 150°-160°C, the hydroxyapatite rod grew very homogeneously perpendicular to the substrate, and the edge of the needle had a flat hexagonal plane. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 387-395, 1998.
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  • 95
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    Journal of Biomedical Materials Research 42 (1998), S. 396-402 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Engineering tissues utilizing biodegradable polymer matrices is a promising approach to the treatment of a number of diseases. However, processing techniques utilized to fabricate these matrices typically involve organic solvents and/or high temperatures. Here we describe a process for fabricating matrices without the use of organic solvents and/or elevated temperatures. Disks comprised of polymer [e.g., poly (D,L-lactic-co-glycolic acid)] and NaCl particles were compression molded at room temperature and subsequently allowed to equilibrate with high pressure CO2 gas (800 psi). Creation of a thermodynamic instability led to the nucleation and growth of gas pores in the polymer particles, resulting in the expansion of the polymer particles. The polymer particles fused to form a continuous matrix with entrapped salt particles. The NaCl particles subsequently were leached to yield macropores within the polymer matrix. The overall porosity and level of pore connectivity were regulated by the ratio of polymer/salt particles and the size of salt particles. Both the compressive modulus (159 ± 130 kPa versus 289 ± 25 kPa) and the tensile modulus (334 ± 52 kPa versus 1100 ± 236 kPa) of the matrices formed with this approach were significantly greater than those formed with a standard solvent casting/particulate leaching process. The utility of these matrices was demonstrated by engineering smooth muscle tissue in vitro with them. This novel process, a combination of high pressure gas foaming and particulate leaching techniques, allows one to fabricate matrices with a well controlled porosity and pore structure. This process avoids the potential negatives associated with the use of high temperatures and/or organic solvents in biomaterials processing. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 396-402, 1998.
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  • 96
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    Journal of Biomedical Materials Research 42 (1998), S. 403-406 
    ISSN: 0021-9304
    Keywords: calcium phosphate cements ; X-ray diffraction ; setting reactions ; bone apatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The setting reactions of calcium phosphate cements in the CaHPO4-α-Ca3(PO4)2 (DCP-α-TCP) system have been investigated. X-ray diffraction (XRD) analyses were performed on DCP-α-TCP cement samples of varying calcium to phosphorus (Ca/P) ratios after setting for 24 h in Ringer's solution at 37°C. XRD measurements showed that the intensity of the DCP peaks decreased linearly as the Ca/P ratio of the mixture increased. However, the intensity of the peaks of a new calcium-deficient hydroxyapatite [CDHA; Ca9(HPO4)(PO4)5OH] precipitating phase increased linearly as the Ca/P ratio increased. Alpha-TCP was not detected after 24 h of setting in any sample. A two-phase mixture XRD model was applied to explain the results, and suitable fits were obtained between observed and expected values of the relevant peak heights. The method used for this study also can be applied to studies of the kinetic behavior of other cement systems. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 403-406, 1998.
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  • 97
    ISSN: 0021-9304
    Keywords: composite materials ; carbon fiber ; implant ; femoral ; bone ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A novel composite material with an ultra-high strength and a low elastic modulus called carbon-fiber-reinforced liquid crystalline polymer (LCP/CF) has been developed. We studied the effects of an intramedullary LCP/CF rod on bone in rabbits. A LCP/CF rod of 3.2 mm in diameter and 50 mm in length was introduced into the intramedullary canal of the right femur in ten rabbits weighing an average of 3.6 (3.1-4.2) kg. The follow-up intervals were 3 and 52 weeks. No signs of deformity or osteopenia were seen in the operated femurs in the radiographic, histological, and histomorphometric studies. Histologically, the implant was enclosed by cancellous bone in the metaphyseal area and by a thin cancellous bone cuff in medullary cavity. Bone was able to grow in direct contact with the LCP/CF rod. No signs of degradation of the implants or of adverse tissue reaction were seen. The intramedullary LCP/CF rod had no harmful effects on bone in rabbits. The biocompatibility of the LCP/CF appeared to be good. This novel composite material demonstrates properties that may be useful in orthopedic applications. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 407-411, 1998.
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  • 98
    ISSN: 0021-9304
    Keywords: latex examination gloves ; cornstarch lubrication ; powder-free gloves ; absorbable dusting powders ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: There are a wide variety of latex examination gloves now available for use by health care providers. A prospective randomized trial was completed to quantify the forces required to don a sample of seven cornstarch-lubricated gloves and 13 powder-free latex examination gloves. The data collected was analyzed by a 20 × 2 general factorial ANOVA, as well as two 1-way ANOVAs using a least significance difference post hoc test. Some powder-free gloves can be easily donned with dry or wet hands without tearing with forces comparable to those encountered with powdered gloves. With the advent of these powder-free examination gloves, powdered gloves can now be abandoned, protecting health professionals and patients from the dangers of absorbable dusting powders. Despite the dangers of the absorbable dusting powders and the Food and Drug Administration's requirement for labeling examination glove boxes, some manufacturers of powdered examination gloves do not appropriately label their boxes with a warning to the health professional and patient of the presence of powder. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 331-337, 1998
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  • 99
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    Journal of Biomedical Materials Research 43 (1998), S. 350-355 
    ISSN: 0021-9304
    Keywords: prostheses-bone interfaces ; histomorphology ; mechanical interlocking ; bone matrix-materials interactions ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In this overview, which is based on selected books and reviews, the microscopic appearances of prosthesis-bone interfaces resulting from clinically relevant implantation techniques are highlighted. The following techniques are distinguished to insert and attach prostheses in the recipient bone: impaction into bone, primary mechanical interlocking, cement fixation, bone ongrowth and secondary mechanical interlocking with bioinert materials, and enhanced bone ongrowth and bone bonding to bioactive materials. The resulting typical histomorphologies of orthopedic and dental prostheses-bone interfaces are described and illustrated from the author's studies employing light, fluorescence, and backscattered electron microscopy, and corresponding microradiographs of undecalcified ground sections of bone and implants. Special emphasis is given to the mineralization-demineralization kinetics of the interfacial bone matrix interacting with specific surface reactions of some implant materials. Consequently, the distinction between bioinert and bioactive prosthetic materials is critically analyzed. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 350-355, 1998
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  • 100
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    Journal of Biomedical Materials Research 43 (1998), S. 380-398 
    ISSN: 0021-9304
    Keywords: bone graft substitute ; osteogenesis ; hyaluronan ; recombinant human bone morphogenetic protein 2 (rhBMP-2) ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: This article presents a strategy for design, engineering, and fabrication of a bioresorbable, manufactured bone graft substitute (BGS) device. The approach is based on established precepts of osteogenesis, molecular biology of hyaluronic acid and osteoinductive proteins, and theoretical preformance criteria for such a device collated from the literature of 1991 to 1996. Application of this design and engineering strategy results in a composite device consisting of a D,D-L,L-polylactic acid macrostructure optimized to the architecture of cancellous bone, a microstructure composed of a filamentous velour of hyaluronan and a recombinant human bone morphogenetic protein 2 (rhBMP-2). The performance of this construct was tested in vivo in the dog, intertransverse process, spinal fusion model and in a critical sized defect of the rabbit radius. Data from these studies are used to illustrate principle points of the design and engineering concept. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 380-398, 1998
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