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  • 1
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    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.
    Additional Material: 8 Ill.
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  • 2
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    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.
    Additional Material: 5 Ill.
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  • 3
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 37 (1997), S. 401-412 
    ISSN: 0021-9304
    Keywords: subcutaneous implants ; sensors ; capsules ; diffusion ; transport barrier ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: This report uses normal rat subcutis as a reference point to provide a quantitative analysis of small analyte transport through the tissue which encapsulates implants. Polyvinyl alcohol (PVA) with 60- and 350-μm mean pore size (PVA-60, PVA-350), nonporous PVA (PVA-skin), and stainless-steel cage (SS) specimens were implanted in the subcutis of Sprague-Dawley rats for 4 weeks to elicit a range of capsular wound-healing tissues. Histologic examination showed that the capsular tissue which formed around PVA-skin and SS specimens was densely fibrous and avascular. That forming around PVA-60 and PVA-350 was less densely fibrous and more vascular. The fibrous content of capsular tissue and subcutis was determined from eosin-stained histologic sections. Dual-chamber diffusion measurements of sodium fluorescein (Mw 376 g/mol) through capsular tissue and normal rat subcutis were used to quantitatively compare the effective diffusion coefficients of small analytes on the order of glucose. The two most fibrous capsular tissues exhibited diffusion coefficients that were statistically (p 〈 0.05) less than that determined for rat subcutis by 50 and 25% for PVA-skin and SS, respectively. The diffusion coefficients of the less dense capsular tissue which formed around the porous implants were not statistically different from subcutis. The experimentally measured diffusion coefficients of the two most fibrous capsular tissues were closely predicted by a simple two-component diffusion model consisting of an aqueous interstitium with an array of impenetrable bodies equal in volume fraction to the fibrous content of the tissue. This model overestimates the diffusion coefficients measured for the least fibrous tissues. Using the diffusion coefficient measured for the PVA-skin capsular tissue, a finite difference model predicts that a 200-μm-thick capsular layer would increase from 5 to 20 min the time required for subcutaneously implanted sensor to detect 95% of the blood analyte concentration. This study suggests that the fibrous capsule forming around a subcutaneously implanted smooth-surface sensor imposes a significant diffusion barrier to small analytes such as glucose, thus increasing the lag time of the sensor by as much as threefold. A corollary observation is that a sensor with a porous surface which allows tissue ingrowth may be more responsive to blood analyte fluctuations as a result of its a more vascular and less fibrous encapsulation tissue. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 37, 401-412, 1997.
    Additional Material: 10 Ill.
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  • 4
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 41 (1998), S. 377-385 
    ISSN: 0021-9304
    Keywords: endothelial cell adhesion ; avidin-biotin ; fibronectin ; total internal reflection fluorescence microscopy (TIRFM) ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A preadsorbed layer of “heterogeneous” integrin-dependent and -independent protein was used to enhance initial integrin-mediated endothelial cell attachment and spreading. Glass substrates were treated with fibronectin (Fn) and avidin coupled through adsorbed biotinylated bovine serum albumin (b-BSA). The slides then were seeded with biotinylated BAEC. Control “homogeneous” surfaces were slides adsorbed with either Fn or avidin coupled to b-BSA. The cells were incubated for 0.5 h in serum-containing media and exposed to a range of shear stresses in a laminar flow variable-height flow chamber. The critical shear stress to detach 50% of the seeded cells on the heterogeneous ligand surface was significantly greater than for either of the control homogeneous ligand systems (p 〈 0.001). Cellular spreading during the initial period of 0-2 h also was higher (p 〈 0.05) on the heterogeneous ligand-treated surface than on the surface of either of the homogeneous controls. The close contact area of the cell membrane with the substrate 1 h after seeding in serum-containing media was measured using TIRFM. Cells attached onto the heterogeneous ligand-treated surfaces had a significantly (p 〈 0.01) higher area of close contact with the substrate, which is consistent with a greater degree of attachment and spreading. The results indicate that the combination of integrin-dependent and -independent adhesion systems using heterogeneous ligands further enhances initial endothelial cell attachment and spreading. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 377-385, 1998.
    Additional Material: 4 Ill.
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