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  • 1
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    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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  • 2
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    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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  • 3
    Electronic Resource
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    Hoboken, NJ : Wiley-Blackwell
    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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  • 4
    Electronic Resource
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 43 (1998), S. 46-53 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; electrophoretic coating ; composite ; alumina ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: By means of an electrophoretic deposition technique followed by sintering, alumina and zirconia ceramics were coated with apatitic composites composed of porous surface and intermediate layers of hydroxyapatite and an adhesive calcium phosphate layer. The electrophoretic deposition of these layers was attained by the use of a mixed solvent of acetylacetone and alcohol as well as the mixed powders of the calcium phosphates and alumina. The adhesive layer was formed by the codeposition of calcium phosphate glass powders (Ca/P = ½) with hydroxyapatite, while the open porosity of the surface layer was increased with the addition of alumina to the hydroxyapatite layers. The resultant phases of sintered composite layers were tricalcium phosphate and alumina with a small amount of hydroxyapatite. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 46-53, 1998
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  • 5
    Electronic Resource
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 43 (1998), S. 77-81 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; porous ceramics ; coating ; interfacial bond ; strength ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A thin film of hydroxyapatite (HA) was successfully coated onto a highly porous substrate of alumina by using a novel solution technique. The coated HA bonded strongly to the substrate through a glass sintering aid with an intermediate thermal expansion coefficient. The coating was also found to be microstructurally and chemically uniform on the surfaces of the interconnected pores in the matrix of the substrate. Mechanical property testing results showed that the strength of the HA-coated composite was significantly improved, indicating a high potential for structural bone substitutes in hard tissue prosthetics. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 77-81, 1998
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  • 6
    ISSN: 0021-9304
    Keywords: calcium phosphate(s) ; brushite ; hydroxyapatite ; calcite ; remodeling ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Four calcium phosphate cement formulations were implanted in the rabbit distal femoral metaphysis and middiaphysis. Chemical, crystallographic, and histological analyses were made at 2, 4, and 8 weeks after implantation. When implanted into the metaphysis, part of the brushite cement was converted into carbonated apatite by 2 weeks. Some of the brushite cement was removed by mononuclear macrophages prior to its conversion into apatite. Osteoclastlike cell mediated remodeling was predominant at 8 weeks after brushite had converted to apatite. The same histological results were seen for brushite plus calcite aggregate cement, except with calcite aggregates still present at 8 weeks. However, when implanted in the diaphysis, brushite and brushite plus calcite aggregate did not convert to another calcium phosphate phase by 4 weeks. Carbonated apatite cement implanted in the metaphysis did not transform to another calcium phosphate phase. There was no evidence of adverse foreign body reaction. Osteoclastlike cell mediated remodeling was predominant at 8 weeks. The apatite plus calcite aggregate cement implanted in the metaphysis that was not remodeled remained as poorly crystalline apatite. Calcite aggregates were still present at 8 weeks. There was no evidence of foreign body reaction. Osteoclastlike cell remodeling was predominant at 8 weeks. Response to brushite cements prior to conversion to apatite was macrophage dominated, and response to apatite cements was osteoclast dominated. Mineralogy, chemical composition, and osseous implantation site of these calcium phosphates significantly affected their in vivo host response. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 451-461, 1998
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  • 7
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 39 (1998), S. 407-414 
    ISSN: 0021-9304
    Keywords: plasma spraying ; amorphous phases ; hydroxyapatite ; coating microstructure ; X-ray diffraction ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The amorphous phase content of air plasma-sprayed hydroxyapatite coatings is dependent upon spraying and deposition conditions. X-ray diffraction and optical microscopy were used to investigate the influence of spray parameters on the formation of the amorphous phase. Results show three factors which most influence the formation of the amorphous phase: dehydroxylation of the molten particle during flight, the cooling rate as it impinges onto the metal substrate, and the substrate temperature. Crystalline regions were identified as unmelted particles and elongated recrystallized areas. Amorphous phase regions vary throughout the coating but are more commonly found at the coating-substrate interface, i.e., the regions decrease toward the surface of the coating. Such an inhomogeneous distribution of phase content is expected to affect the clinical process of bone deposition, and therefore successful implant fixation. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 407-414, 1998.
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  • 8
    Electronic Resource
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 39 (1998), S. 580-587 
    ISSN: 0021-9304
    Keywords: plasma spraying ; hydroxyapatite ; decomposition ; vaporization ; amorphous ; X-ray diffraction ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Thermally processed hydroxyapatite coatings used on dental implants and hip prostheses for enhanced fixation may typically consist of a number of chemical and structural phases. These phases affect coating performance and tissue attachment. Hydroxyapatite was plasma sprayed to examine the phase evolution during processing. Coatings were examined with X-ray diffraction and elemental analysis. Results indicate that phase transformations are produced by (a) preferential removal of hydroxyl and phosphate leading to a change in melt composition, and (b) the high cooling rate due to the thermal spray process. Hydroxyl group removal promotes the amorphous phase and oxyapatite. Further heating produces a less viscous melt facilitating decomposition of hydroxyapatite to tricalcium and tetracalcium phosphate. Phosphate removal during flight produces a more calcium-rich melt preferring tetracalcium phosphate and calcium oxide formation. A proposed model shows the phase location within the lamellae of these coatings. Coating processes must thus prevent removal of hydroxide and phosphate during processing to maximize the hydroxyapatite content. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 580-587, 1998.
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  • 9
    ISSN: 0021-9304
    Keywords: antibiotics ; calcium phosphate cement ; drug delivery system ; hydroxyapatite ; anti-washout type ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The effect of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement (aw-FSCPC) was investigated in a preliminary evaluation of aw-FSCPC containing drugs. Flomoxef sodium was employed as the antibiotic and was incorporated into the powder-phase aw-FSCPC at up to 10%. The setting time, consistency, wet diametral tensile strength (DTS) value, and porosity were measured for aw-FSCPC containing various amounts of flomoxef sodium. X-ray diffraction (XRD) analysis was also conducted for the identification of products. To evaluate the drug-release profile, set aw-FSCPC was immersed in saline and the released flomoxef sodium was determined at regular intervals. The spread area of the cement paste as an index of consistency of the cement increased progressively with the addition of flomoxef sodium, and it doubled when the aw-FSCPC contained 8% flomoxef sodium. In contrast, the wet DTS value decreased with increase in flomoxef sodium content. Bulk density measurement and scanning electron microscopic observation revealed that the set mass was more porous with the amount of flomoxef sodium contained in the aw-FSCPC. The XRD analysis revealed that formation of hydroxyapatite (HAP) from aw-FSCPC was reduced even after 24 h, when the aw-FSCPC contained flomoxef sodium at ≥6%. Therefore, the decrease of wet DTS value was thought to be partly the result of the increased porosity and inhibition of HAP formation in aw-FSCPC containing large amounts of flomoxef sodium. The flomoxef sodium release from aw-FSCPC showed the typical profile observed in a skeleton-type drug delivery system (DDS). The rate of drug release from aw-FSCPC can be controlled by changing the concentration of sodium alginate. Although flomoxef sodium addition has certain disadvantageous effects on the basic properties of aw-FSCPC, we conclude that aw-FSCPC is a good candidate for potential use as a DDS carrier that may be useful in surgical operations. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 308-316, 1998.
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  • 10
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 39 (1998), S. 390-397 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; particle size ; osteoblasts ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Over the past decade, a large number of biomaterials have been proposed as artificial bone fillers for repairing bone defects. The material most widely used in clinical medicine is hydroxyapatite. The aim of our investigation was to study the effect of hydroxyapatite size mechanism on osteoblasts.The osteoblasts were cultured in vitro with 0.1% (1 mg/mL) of various sized hydroxyapatite particles (0.5-3.0, 37-63, 177-250, and 420-841 μm) for 1 h, 3 h, 1 day, 3 days, and 7 days. The results showed that adding hydroxyapatite particles to osteoblast cultures can significantly affect osteoblast cell count. Osteoblast populations decreased significantly. Osteoblast mean surface areas also changed significantly. Transforming growth factor-β1 (TGF-β1) concentrations in culture medium decreased significantly with the addition of hydroxyapatite particles. Prostaglandin E2 (PGE2) concentrations in medium increased significantly. The changes in TGF-β1 and PGE2 concentration were more significant and persisted longer in smaller-particle groups. The inhibitory effects of hydroxyapatite particles on osteoblast cell cultures were mediated by the increased synthesis of PGE2. Caution should be exercised before using a hydroxyapatite product which could easily break down into fine particles. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 390-397, 1998.
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  • 11
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 40 (1998), S. 358-364 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; hydroxyl groups ; hexamethylene diisocyanate ; isocyanatoethyl methacrylate ; coupling agents ; surface modification ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The surface grafting reactions of a series of isocyanates with hydroxyapatite particles at different temperatures were studied by Infrared spectrophotometry (IR) and thermal gravimetric analysis (TGA). The study results show that both hexamethylene diisocyanate (HMDI) and isocyanatoethyl methacrylate (ICEM) react readily with HA while ethyl isocyanate acetate (EIA) and butyl isocyanate (BIC) have lower reactivity towards HA particles. It also has been found that the reaction of ICEM with HA follows a second-order reaction mechanism, despite the heterogeneous nature of the reaction, while the reaction of HMDI with HA does not due to the complexity of the reaction. Based on this study, it is concluded that ICEM and HMDI are suitable agents for the coupling of polymers due to their reactivity towards HA. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 358-364, 1998.
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  • 12
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 40 (1998), S. 407-413 
    ISSN: 0021-9304
    Keywords: amorphous phase ; nanocrystalline ; plasma spraying ; hydroxyapatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Study of an amorphous phase in plasma-sprayed hydroxyapatite (HA) coatings is important owing to its unique characteristics and nonnegligible amount of the amorphous phase compared to crystalline HA. However, little is known about the component parts of an amorphous phase. It is known that amorphous phase usually appears as the diffusion maximum (Dmax) in X-ray diffraction (XRD) patterns. Analyzing Dmax, including the position (Pmax) and area of Dmax, we can indicate the component parts of an amorphous phase and their transitions. In this study, the variation of Dmax in XRD patterns of the coatings during plasma spraying, in postheating, and in dissolving in vitro was studied with the aid of XRD. It was found that component parts of the amorphous phase in the coating varied with increasing thickness, consisting of two parts represented by Dmax1, located between 29.4 and 29.8 degrees (2θ), and Dmax2, located between 31.0 and 31.4 degrees (2θ). It was concluded that Dmax3, located between 32.0 and 32.4 degrees (2θ), should be referred to as nanocrystals of HA. In addition, the particle size of the starting powder may affect the component parts of the amorphous phase in the coating in addition to thickness. With vacuum heating (650°C) and water vapor treatment at a low temperature (125°C) in a saturated vaporic atmosphere, transition of the amorphous components was not as efficient as that at 490°C with water vapor. The reason might be that the amorphous-to-crystalline HA conversion is dependent on both temperature and water vapor pressure. It was found that amorphous components were transformed completely into crystalline HA after heating at 490°C with a partial water vapor pressure of 0.01 MPa for 2 h. It was concluded that the unstable amorphous components (Dmax1, Dmax2) converted into more stable nanocrystals of HA (Dmax3). Degradation in vitro showed that Dmax3 was more stable than Dmax1 and Dmax2. It was concluded that nucleation of apatite in vitro should be attributed to nanocrystals of HA (Dmax3) except for the amorphous components. It is recommended that the optimal phasic contents of the plasma-sprayed HA coating be mainly composed of crystalline HA and nanocrystals of HA (Dmax3) in terms of the stability and biocompatibility of the coating. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 407-413, 1998.
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  • 13
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 41 (1998), S. 541-548 
    ISSN: 0021-9304
    Keywords: apatite ; chitin ; in situ precipitation ; hydroxyapatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Composites of chitin with calcium phosphate were obtained by in situ precipitation of the mineral from a supersaturated solution onto chitin scaffolds. The chitin scaffolds were obtained by freeze drying to give a highly porous structure possessing a polar surface favorable for apatite nucleation and growth. The extent and arrangement of calcium phosphate deposits on the chitin and substituted chitin scaffolds were explored. Up to 55% by mass of calcium phosphate could be incorporated into chitin scaffolds. Deposits on the chitin surface were of a continuous apatite carpet nature while deposits on carboxymethylated chitin surfaces displayed a spherical morphology. Carboxymethylation of chitin exerts an overall inhibitory effect towards calcium phosphate deposition, but it provides for site-specific nucleation of the mineral phase. In situ precipitation can be an important route in the future production of various polymer-calcium phosphate composites. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 541-548, 1998.
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  • 14
    ISSN: 0021-9304
    Keywords: bioactive bone cement ; apatite-wollastonite-glass-ceramic ; hydroxyapatite ; β-tricalcium phosphate; bone-bonding strength ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A study was conducted to compare the bone-bonding strengths of three types of bioactive bone cement, consisting of either apatite- and wollastonite-containing glass-ceramic (AW-GC) powder, hydroxyapatite (HA) powder, or β-tricalcium phosphate (β-TCP) powder as an inorganic filler and bisphenol-a-glycidyl methacrylate (Bis-GMA) based resin as an organic matrix. Seventy percent (w/w) filler was added to the cement. Rectangular plates (10 × 15 × 2 mm) of each cement were made and abraded with #2000 alumina powder. After soaking in simulated body fluid for 2 days, the AW cement (AWC) and HA cement (HAC) formed bonelike apatite over their entire surfaces, but the TCP cement (TCPC) did not. Plates of each type of cement were implanted into the tibial metaphyses of male Japanese white rabbits, and the failure loads were measured by a detaching test at 10 and 25 weeks after implantation. The failure loads of AWC, HAC, and TCPC were 3.95, 2.04, and 2.03 kgf at 10 weeks and 4.36, 3.45, and 3.10 kgf at 25 weeks, respectively. The failure loads of the AWC were significantly higher than those of the HAC and TCPC at 10 and 25 weeks. Histological examination by contact microradiogram and Giemsa surface staining of the bone-cement interface revealed that all the bioactive bone cements were in direct contact with bone. However, scanning electron microscopy and energy-dispersive X-ray microanalysis showed that only AWC had contacted to the bone via a Ca-P rich layer formed at the interface between the AW-GC powder and the bone, which might explain its high bone-bonding strength. Neither the HAC nor the TCPC contacted the bone through such a layer between each powder and the bone, although the HAC and TCPC directly contacted with bone. Our results indicate that all three types of abraded and prefabricated cement have bonding strength to bone, but AWC has superior bone-bonding strength compared to HAC and TCPC. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 223-237, 1998.
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  • 15
    ISSN: 0021-9304
    Keywords: BMP ; geometry ; carriers ; hydroxyapatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Bone morphogenetic protein (BMP) is known to require a suitable carrier to induce ectopic bone formation in vivo. Hydroxyapatite ceramics have been reported to be effective in some forms but ineffective in others as a carrier of BMP-induced bone formation. In this study we compare three geometrically different forms of hydroxyapatite to examine their functions as carriers of BMP-induced bone formation. A fraction containing all the active BMPs (BMP cocktail) was partially purified from a 4M guanidine extract from bovine bone by a three-step chromatographic procedure. The BMP cocktail was combined with each of three forms of hydroxyapatite - solid particles (SPHAP), porous particles (PPHAP), and coral-replicated porous tablets (coral-HAP) - and implanted subcutaneously into rats. Both the PPHAP and coral-HAP systems induced osteogenesis 2 weeks after implantation, as evidenced by morphological and biochemical observations. Details of the osteogenetic process were followed by double-fluorescence labeling in the coral-HAP system to confirm bone formation on the surface of hydroxyapatite. However, there was no evidence of osteogenesis or chondrogenesis in the SPHAP system. The results indicate that the geometry of the interconnected porous structure in PPHAP and coral-HAP create spaces for vasculature that lead to osteogenesis while the smooth structure and close contact of particles in SPHAP inhibit vascular formation and proliferation of mesenchymal cells, preventing bone and cartilage formation. It was concluded that the geometrical structure in hydroxyapatite ceramics that induces vasculature is crucial as a carrier for BMP-induced bone formation. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 190-199, 1998.
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  • 16
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 41 (1998), S. 79-86 
    ISSN: 0021-9304
    Keywords: carbonate ; hydroxyapatite ; substitution ; precipitation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Carbonate substitution in the apatite crystal lattice can occur in either the hydroxyl or the phosphate sites, designated as A or B type, respectively, and previous investigations generally have described precipitated carbonate hydroxyapatite as being B type on the basis of infra red and X-ray data. This paper documents the effects of two precipitation variables, namely temperature and bicarbonate ion concentration, on the morphology, phase composition, and calcium, phosphorus, and carbon contents of precipitated carbonate hydroxyapatite. Variations in both temperature and bicarbonate concentration could yield either acicular or spheroidal crystals. X-ray diffraction and infra red spectroscopy indicated the presence of carbonate in the A site for low carbonate contents (〈 4 wt%), and at higher carbonate contents (〉 4 wt%), the carbonate was located predominantly in the B site. On the basis of these observations and chemical analyses, a new AB carbonate substitution mechanism is proposed that better describes the experimental data than the B-type models used previously. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 79-86, 1998.
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  • 17
    ISSN: 0021-9304
    Keywords: bone morphogenetic protein-2 ; hydroxyapatite ; osseointegration ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To determine if recombinant human bone morphogenetic protein-2 (rhBMP-2) can be adsorbed onto porous ceramic hydroxyapatite (HA) and promote the integration of HA to host bone, 54 subperiosteal pockets were created on the skulls of 19 adult Pasteurella-free white rabbits. Fourteen HA implants were saturated with saline and placed in subperiosteal pockets (control), 22 HA implants were saturated with saline and placed into subperiosteal pockets after burring 1-2 mm of calvarium to expose bleeding cancellous bone, and 18 HA implants were saturated with rhBMP-2 and placed into subperiosteal pockets. The animals were sacrificed at 1 month with examination to determine implant mobility. Histology was used to determine the amount of bone growth into the implant. Of the 14 control sites, 10 implants were found to be freely mobile, five demonstrated host bone resorption, and only one exhibited bone growth into the implant. Of the 22 burred sites, eight were freely mobile and 10 demonstrated bone growth into the implant (p = 0.04). Of the 18 rhBMP-2 sites, only two were freely mobile, none demonstrated host bone resorption, and 16 exhibited bone growth into the implant (p = 0.00002). This study supports the use of porous ceramic HA as a biocompatible, osteoconductive implant material for use in craniomaxillofacial augmentation and reconstruction. It also provides evidence that rhBMP-2 enhances osseointegration, thereby fixing the implant in position against the host-bone interface. In the clinical setting, osseous fixation of the implant should aid in preventing displacement, minimizing host bone resorption, and decreasing the incidence of extrusion. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 359-363, 1998.
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  • 18
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    Journal of Biomedical Materials Research 42 (1998), S. 458-464 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; fluorapatite ; tricalcium phosphate ; kinetics ; hydrolysis ; fluoridation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Although there is interest in forming synthetic analogs of hard tissues at physiologic temperature, significant gaps in knowledge exist with respect to the mechanisms by which precursor solids convert to apatites and also with respect to the apatite compositions that may be formed. In this study calcium-deficient HAp [Ca9(HPO4)(PO4)5OH] was prepared by hydrolysis of tricalcium phosphate (TCP), α-Ca3(PO4)2. The kinetics of HAp formation were studied as a function of temperature by isothermal calorimetry. TCP hydrolyzed completely within about 12 h, and the hydrolysis reaction evolved 133 kJ/mol of HAp formed. Although the kinetics of hydrolysis exhibited a strong temperature dependence, the mechanistic path taken appeared independent of temperature. The fluoridation of hydroxyapatite compositions having Ca/P ratios higher than 1.59 previously has been investigated. However, little work has been done on the fluoridation of more calcium-deficient hydroxyapatite. Ca9(HPO4)(PO4)5OH was formed at temperatures between 37.4° and 55°C to vary its morphology. These preparations then were reacted in NaF solution and the kinetics of fluoride incorporation studied. Solution chemical analyses were used to determine the amounts of fluoride incorporated. The extent of hydroxyl replacement by fluoride ranged from 17 to 72% and correlated with the surface area of the parent HAp. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 458-464, 1998.
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  • 19
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    Journal of Biomedical Materials Research 43 (1998), S. 399-409 
    ISSN: 0021-9304
    Keywords: amorphous calcium phosphate ; bone substitute ; bone graft ; hydroxyapatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The in vitro and in vivo properties of a novel, fully resorbable, apatitic calcium phosphate bone substitute (ABS) are described. The ABS was prepared from calcium phosphate precursors that were hydrated to form an injectable paste that hardens endothermically at 37 °C to form a poorly crystalline apatitic calcium phosphate (PCA). The PCA reaction product is stable in vivo as determined by FTIR and XRD analysis of rabbit intramuscular implants of ABS retrieved 4, 7, and 14 days postimplantation. Bone formation and resorption characteristics of the ABS material were characterized in a canine femoral slot defect model. Femoral slot defects in dogs were filled with either autologous bone implants or the ABS material. Sections of femoral bone defect site from animals sacrificed at 3, 4, 12, 26, and 52 weeks demonstrated that new bone formation proceeded similarly in both autograft and ABS filled slots. Defects receiving either material were filled with trabecular bone in the first 3 to 4 weeks after implantation; lamellar or cortical bone formation was well established by week 12. New bone formation in ABS filled defects followed a time course comparable to autologous bone graft filled defects. Histomorphometric evaluation of ABS resorption and new bone formation indicated that the ABS material was greater than 99% resorbed within 26 weeks; residual ABS occupied 0.36 ± 0.36% (SEM, n = 4) of the original defect area at 26 weeks. Quantitatively and qualitatively, the autograft and ABS were associated with similar new bone growth and defect filling characteristics. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 43: 399-409, 1998
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  • 20
    ISSN: 0021-9304
    Keywords: fluorapatite ; hydroxyapatite ; implant ; resorption ; stereology ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Resorption (defined as loss of ceramic coating because of cellular activity or dissolution) of ceramic coatings is a matter of concern for the long-term performance of ceramic-coated implants. A new fluorine-containing coating, fluorapatite (FA), has been shown to be more stable than hydroxyapatite (HA) in unloaded models. In a weight-bearing model in trabecular bone, we evaluated loss (defined as reduction of coating irrespective of type of mechanism) of HA and FA coatings during 25 weeks of implantation. Eight mature dogs had HA- or FA-coated implants inserted bilaterally into the weight-bearing region of the medial femoral condyle. Quantified loss of ceramic coating was estimated at the light microscopic level using stereological methods. The experiment showed significant loss of both types of coatings. However, no statistical difference in loss of ceramic coating was found regarding surface area, implant coverage, volume, and thickness (p = 0.77, p = 0.13, p = 0.56, p = 0.23, respectively). Completely resorbed HA coating was replaced by 36 ± 6.0% (range: 26-42) bone in direct contact with the implant surface compared with 29 ± 16.0% (range: 12-59) for FA (p = 0.40), suggesting that the implant was firmly fixed despite loss of the ceramic coating. Transmission electron microscopy in combination with electron energy spectroscopy and electron spectroscopic imaging showed that osteclast-like cells, osteocytes, macrophage-like cells, and fibroblasts had phagocytosed calcium-containing fragments, indicating cell-mediated resorption of the ceramic coating. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 141-152, 1998.
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  • 21
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    Journal of Biomedical Materials Research 39 (1998), S. 176-183 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; crystallinity ; materials characterization ; alkaline phosphatase activity ; osteocalcin concentration ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The clinical success of dental implants is governed by implant surfaces and bone cell responses that promote rapid osseointegration and long-term stability. The specific objective of this study was to investigate osteoblast precursor cell responses to hydroxyapatite (HA) surfaces of different treatments. Since the nature of bone cell responses in vitro is influenced by the properties of HA ceramics, this study was divided into two components: a chemical and crystallographic characterization of the HA ceramics and an in vitro cell culture study. The sintered HA samples were observed to have the highest crystallite size as compared to the as-received HA and calcined HA samples. No differences in the surface roughness and chemical composition were observed among the sintered, calcined, and as-received HA surfaces. In concurrence with the X-ray diffraction, high resolution XPS resolution of Ca 2p also indicated a higher crystallinity on sintered HA samples as compared to the calcined and as-received HA samples. As indicated by increased alkaline phosphatase-specific activity, increased cell-surface and matrix-associated protein, and 1,25 (OH2) vitamin D3-stimulated osteocalcin production, a more differentiated osteoblast-like phenotype was observed on the sintered HA surfaces compared to the as-received HA and calcined HA surfaces. An increased osteoblast-like cell activity on the sintered HA surfaces suggested that the crystallite size of HA surfaces may play an important role in governing cellular response. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 176-183, 1998.
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  • 22
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    Journal of Biomedical Materials Research 40 (1998), S. 171-179 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; titanium ; calvarial cells ; cell-specific alkaline phosphatase activity ; bone-related proteins gene expression ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Rat calvarial cell mitogenic behavior was investigated on various biomaterials coated with Matrigel®, a basement membrane matrix containing growth factors. Low (20-40%) and high (70-90%) crystallinity hydroxyapatite (rHA and cHA), rough titanium (Ti), and tissue culture polystyrene (TP) surfaces were compared. Surface chemistry and calcium resorption of HA coatings, alkaline phosphatase activity (APA), and growth of cells were measured for Matrigel®-coated and uncoated surfaces at 2, 7, and 14 days. Gene expression for four noncollagenous bone-related proteins (osteonectin, osteopontin, alkaline phosphatase, and osteocalcin) was also investigated by reverse transcription and polymerase chain reaction up to 28 days. Ca concentration in incubating solutions increased with time for the two types of HA coatings and was always greater for rHA than cHA. Surface chemistry and coating dissolution rates were not affected by the presence of Matrigel® or cells throughout the study. APA of cells on the two HA-coated surfaces was comparably enhanced in the presence of Matrigel® and was greater than on Ti surfaces. Only HA surfaces showed an increased APA of cells with time in the presence of Matrigel®. Cell growth peaked at 7 days and was greatest for cells on the two HA surfaces and without Matrigel®. At 14 days, cell growth was comparable on the four surfaces. The presence of HA and Matrigel® enhanced cell-specific APA at 14 days. Gene expression for all four proteins investigated showed no differences between surfaces after 7 days. At 2 and 7 days, gene expression was indicative of proliferation for Ti, and of proliferation, differentiation, and mineralization for HA and TP more so without Matrigel®. The addition of this matrix significantly enhanced mitogenicity of calvarial cells on HA only after 14 days. Matrigel® eliminated differences seen between the two HA coatings. Gene expression was not enhanced or inhibited by the presence of Matrigel®. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 171-179, 1998.
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  • 23
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    Journal of Biomedical Materials Research 40 (1998), S. 48-56 
    ISSN: 0021-9304
    Keywords: bioactive glass ; hydroxyapatite ; cell adhesion ; fibronectin ; protein conformation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Bioactive glasses and ceramics enhance bone formation and bond directly to bone, and have emerged as promising substrates for bone tissue engineering applications. Bone bioactivity involves physicochemical surface reactions and cellular events, including cell attachment to adsorbed extracellular matrix proteins. The effects of fibronectin (Fn) adsorption and glass surface reaction stage on the attachment of osteoblast-like cells (ROS 17/2.8) to bioactive glass were analyzed. Bioactive glass disks were pretreated in a simulated physiologic solution to produce three reaction layers: unreacted glass (BG0), amorphous calcium phosphate (BG1d), and carbonated hydroxyapatite (BG7d). Synthetic hydroxyapatite (sHA) and nonreactive borosilicate glass (CG) were used as controls. A spinning disk device which applied a linear range of forces to attached cells while maintaining uniform chemical conditions at the interface was used to quantify cell adhesion. The number of adherent cells decreased in a sigmoidal fashion with applied force, and the resulting detachment profile provided measurements of adhesion strength. For the same amount of adsorbed Fn, cell adhesion was higher on surface-reacted bioactive glasses (BG1d and BG7d) than on BG0, CG, and sHA. For all substrates, cell attachment was primarily mediated by the RGD binding site of Fn, as demonstrated by blocking experiments with antibodies and RGD peptides. Cell adhesion strength increased linearly with adsorbed Fn surface density. Analysis of this fundamental relationship revealed that improved adhesion to reacted bioactive glasses resulted from enhanced cell receptor-Fn interactions, suggesting substrate-dependent conformational changes in the adsorbed Fn. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 48-56, 1998.
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  • 24
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    Journal of Biomedical Materials Research 40 (1998), S. 257-263 
    ISSN: 0021-9304
    Keywords: poly(methyl methacrylate) ; poly(butyl methacrylate) ; poly(hydroxyethyl methacrylate) ; surface grafting ; hydroxyapatite ; composites ; bone cement ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In our earlier study, we showed that the surface hydroxyl groups of hydroxyapatite have the ability to react with organic isocyanate groups. In this study, the feasibility of grafting poly(methyl methacrylate) (PMMA), poly(n-butyl methacrylate) (PBMA), and Poly(hydroxyethyl methacrylate) [poly(HEMA)] by using the reaction of isocyanate groups with the hydroxyl groups on the surface of HA was investigated. Double bonds were introduced to the surface of HA via the coupling reaction of isocyanateoethyl methacrylate (ICEM) with HA, or through hexamethylene diisocyanate (HMDI) with hydroxyethyl methacrylate (HEMA) and HA, followed by radical polymerization in MMA, BMA, or HEMA. Infrared spectra indicated the existence of polymers on the surfaces of HA. Thermogravimetric analysis also confirmed the presence of grafted polymers on the surface of HA powder particles (20-26 wt%). The polymers gave typical PMMA, PBMA, or poly(HEMA) infrared spectra, with the exception of amide bands, a result of the coupling reaction of ICEM or HMDI with hydroxy groups of HA or HEMA. Therefore it is concluded that the polymers were chemically bonded to the surface of HA through the isocyanate groups of ICEM or HMDI. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 257-263, 1998.
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  • 25
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    Journal of Biomedical Materials Research 40 (1998), S. 490-497 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; Polyactive™ ; composites ; interface ; mechanical properties ; surface grafting ; coupling agent ; diisocyanate ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In an effort to make composites from hydroxyapatite and a PEG/PBT copolymer (Polyactive™ 70/30), chemical linkages were introduced between the filler particles and polymer matrix using hexamethylene diisocyanate as a coupling agent. Infrared spectra (IR) and thermal gravimetric analysis (TGA) confirmed the presence of Polyactive™ 70/30 on the surface of HA filler particles. The amount of chemically bound polymer was 4.7 wt.%, as determined by TGA. The mechanical properties of the composites, that is, tensile strength and Young's modulus, were improved significantly by the introduction of a chemical linkage between the filler particles and polymer matrix compared to control composites. This method provides an effective way to introduce chemical linkage between HA filler particles and a polymer matrix. By optimizing the grafting process, a further improvement of the mechanical properties in the composites can be expected. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 490-497, 1998.
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  • 26
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    Keywords: hydroxyapatite ; marrow cell ; dexamethasone ; osteocalcin ; alkaline phosphatase ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: We investigated the in vivo osteogenic ability of cultured marrow cells subcultured in porous hydroxyapatite. This osteogenic ability was compared with that of cancellous bone grafts. Fresh marrow cells were obtained from young adult rat femora and cultured in a standard medium for 10 days, then trypsinized and used to make constructs of porous hydroxyapatite (HA) and cultured marrow cells. An additional 2-week culture (subculture) was performed for the construct in standard medium with and without the addition of dexamethasone (Dex). The 2-week subcultured constructs then were implanted into subcutaneous sites of syngeneic rats. These implants and the rat cancellous bone were harvested and prepared for gene expression analysis of alkaline phosphatase (ALP) and osteocalcin (OC) as well as for histological analysis. ALP and OC mRNAs could be detected in Dex-treated subcultured constructs 1 week after implantation, with an increase at 2 weeks, comparable to the observation in cancellous bone. Histological analysis showed active bone formation even 1 week postimplantation. In contrast, the subcultured constructs without the addition of Dex did not show bone formation, and only small levels of ALP and OC mRNAs were found. These results indicate that the bone tissue formed by grafting the Dex-treated construct of cultured marrow cells and hydroxyapatite possesses a high osteoblastic activity comparable to that of viable cancellous bone. Thus the prefabricated osteogenic subcultured marrow/HA construct may be applicable in bone reconstructive surgery. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 568-573, 1998.
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  • 27
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    Journal of Biomedical Materials Research 42 (1998), S. 412-416 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; hydroxyapatite/bone bonding ; hydroxyapatite/bone stability ; homo/heterocoagulation ; hydroxyapatite/bone surface potentials ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Electroacoustic measurements of the zeta (ζ) potential as a function of pH were collected and used to probe the nature of the ionic contributions to the bond formed between synthetic hydroxyapatite (HA) and bone. HA powder and wet bone powder were dispersed into an electrolyte solution comprised of physiologic saline (0.154M NaCl), electroacoustic measurements collected, and the ζ potential calculated as a function of pH. The ζ potential and particle size then were used to calculate the stability of the composite dispersion, where stability is the ability of a particulate suspension to remain unagglomerated. The stability was used to predict the homo- (HA to HA and bone to bone) versus heterocoagulation (HA to bone) behaviors for the HA/bone system. Although single component bone and HA demonstrated stability against agglomeration, the HA/bone interaction was determined to be unstable for all pH levels tested, including pH 7.4, the normal in vivo pH. These results establish one factor responsible for the observed physicochemical bonding between bone and HA noted by many in the orthopedic community. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 412-416, 1998.
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  • 28
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    Journal of Biomedical Materials Research 36 (1997), S. 306-314 
    ISSN: 0021-9304
    Keywords: magnesium ; hydroxyapatite ; calcium phosphate cement ; inhibition ; amorphous calcium phosphate ; nucleation and growth ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Calcium-deficient hydroxyapatite (HA) with a Ca/P molar ratio of 1.50 was synthesized in various concentrations (0.01-75 mM) of MgCl2 at 37.4°C by reaction between particulate CaHPO4 · 2H2O and Ca4(PO4)2O. The effects of magnesium on the kinetics of HA formation were determined using isothermal calorimetry. All reactions completely consumed the precursor phases as indicated by X-ray diffraction analysis and a constant enthalpy of reaction (240 kJ/mol). Magnesium concentrations below 1 mM had no effect on the kinetics of HA formation. Magnesium concentrations between 1 and 2.5 mM affected the reaction path but did not affect the time required for complete reaction. Higher concentrations extended the times of complete reaction due to magnesium adsorption on the precursor phase(s) and HA nuclei, and stabilization of a noncrystalline calcium phosphate (NCP). HA formation in the presence of magnesium resulted in separation of the following two events: initial formation of HA nuclei and NCP, and consumption of CaHPO4 · 2H2O. This was indicated by the appearance of an additional calorimetric peak. Variations in calcium, magnesium, and phosphate concentrations and pH with time were determined. Increasing the magnesium concentration resulted in elevated calcium concentrations. After an initial decrease in magnesium owing to its adsorption onto HA nuclei and precursor(s), a period of slow reaction at constant magnesium concentration was observed. Both the magnesium concentration in solution and the proportions of precursors present decreased prior to any evidence of a crystalline product phase. This is attributed to the formation of NCP capable of incorporating magnesium. This noncrystalline phase persisted for more than 1 year for reactions in magnesium concentrations about 2.5 mM. Its conversion to HA resulted in the release of magnesium to the solution. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res., 36, 306-314, 1997.
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  • 29
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    Journal of Biomedical Materials Research 37 (1997), S. 122-129 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; bone marrow ; osteogenesis ; immunohistochemistry ; in situ hybridization ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To analyze the bone-bonding property of hydroxyapatite ceramics (HA), composites of rat marrow cells and porous HA were implanted subcutaneously and harvested at 3 to 4 weeks postimplantation. De novo bone formation was observed primarily on the HA surface without fibrous tissue interposition. The HA/tissue interface was analyzed by the observations of thin undecalcified histological sections and fractured surfaces of the implants. The observations were done with a light microscope and a scanning electron microscope (SEM) connected to an energy dispersive spectrometer. The interfacial analyses showed the appearance of osteoblastic cells on the HA surface and that the cells had initiated partially mineralized bone (osteoid) formation directly onto the surface. The osteoid matured into fully mineralized bone, resulting in firm bone bonding to the HA surface. Characterization of osteoblastic cells on the surface was done by determining levels of protein and gene expression of bone Gla protein (BGP, a.k.a. Osteocalcin), i.e., immunohistochemistry and in situ hybridization, respectively. The existence of BGP and mRNA in the cytoplasmic area of the cells confirmed that active osteoblast apposition fabricated primary bone on the HA surface. All of these results indicate the importance of the HA surface in supporting osteoblastic differentiation of marrow stromal stem cells, which leads to firm bone bonding. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 37, 122-129, 1997.
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  • 30
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    Journal of Biomedical Materials Research 38 (1997), S. 11-16 
    ISSN: 0021-9304
    Keywords: adhesive bone cement ; 4-META ; hydroxyapatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Bone response to hydroxyapatite (HA) fillers in the cured 4-methacryloyloxyethyl trimellitate anhydride (4-META)/methyl methacrylate (MMA)-tri-n-butyl borane (TBB) adhesive bone cement was examined mechanically and histologically. A two-component system, consisting of powder and liquid, was formulated. The liquid portion was 5% 4-META dissolved in MMA and TBB; the powder was composed of 50 wt% poly(MMA) (PMMA) and 50 wt% dense HA fillers. The results indicated that the tensile strength decreased with the increase of HA filler size. The bone-bonding behavior of the improved cement was examined by optical microscopy and scanning electron microscopy. Seventy-two implants in six dogs for up to 24 weeks showed 4-META cement filled with HA was stable in the cement-bone interface. Histologic examinations showed that the exposed HA particles at the surface of the cured cement were generally associated with intimate attachment to bone without fibrous tissue, as well as interdigitation of cement to bone. The results suggest the importance of HA fillers in inducing bone apposition that improves cement binding to bone for long-term stability, thereby complementing rapid initial bone fixation of the cement. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 38: 11-16, 1997
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  • 31
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    Journal of Biomedical Materials Research 36 (1997), S. 265-273 
    ISSN: 0021-9304
    Keywords: bone ; titanium ; hydroxyapatite ; polyactive ; gap ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In order to study bone growth conducting capacities of new biomaterials under standardized conditions, a goat model was developed based on a canine model by Soballe. Titanium alloy implants with and without a hydroxyapatite coating were used as positive and negative controls, and these were implanted with a circumferential gap of one millimeter in the spongious bone of the knee condyles of two groups of four goats. These goats were sacrificed at 6 and 25 weeks. A second experiment was done on two groups of four goats with the same type of titanium alloy and hydroxyapatite-coated implants as controls and with Polyactive® 55-45 coated titanium alloy implants for testing. These goats were sacrificed at 9 and 25 weeks, respectively. Qualitative and quantitative differences in gap healing were evaluated through light microscopy, and initiation and direction of bone apposition were determined with fluorescence microscopy. Apposition of bone was seen directly on all hydroxyapatite surfaces and on some of the noncoated titanium alloy surfaces. The difference between the percentage of bone growth on the titanium alloy implants and the hydroxyapatite-coated implants appeared to be divergent in time: the bone growth on the noncoated implants declined after 9 weeks in contrast to the steady increase of bone growth on the hydroxyapatite-coated implants towards the 25 week follow-up time (p = 0.02). No significant difference was found between the first and the second experiment: apposition of bone on the implants differed only 6.6% on a scale of 0% to 100%. Only scarce bone growth was seen on the polyactive-coated implants in this model. The newly tested Polyactive® 55-45 coating apparently needs initial bone contact for bone-bonding and therefore showed hardly any direct bone formation on its surface. The clear differences in the reaction of bone to the coated and noncoated implants in this goat study and the reproducibility of these reactions of bone to the different controls indicate the sensitivity of the currently used animal model and its suitability for use as a bioactivity assay. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 36, 265-273, 1997.
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    Journal of Biomedical Materials Research 37 (1997), S. 1-8 
    ISSN: 0021-9304
    Keywords: osteoblasts ; culture system ; hydroxyapatite ; three-dimensional configuration ; mineralization ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In vitro bone formation by cells derived from adult rabbit femurs was investigated on or in several substrates with small porous hydroxyapatite granules (HAGs). When the bone fragments were cultured in HAG-packed glass tubes, which were inclined (5°-30°) and rotated 90 degrees per day after one week of culture, thin lamellar tissues were newly formed in narrow spaces among the HAGs. By 11 days of culture, these tissues had been mineralized except for their periphery and had well developed collagen bundles and several monolayer cells. Some cells resided in bone lacuna-like spaces. By contrast, mineralization was negligible in 6-week cultures on two-dimensional glass and polystyrene plates with or without two-dimensionally arranged HAGs on their surfaces and in three-dimensional collagen gels with or without HAGs in spite of active cell proliferation. These results suggest that osteogenesis is accelerated in a specific three-dimensional constitution of extracellular matrix and/or under the effects of mechanical forces for the new tissue and that bioactive HAGs offer favorable three-dimensional spaces for osteogenic tissue formation. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 37, 1-8, 1997.
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  • 33
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    Journal of Biomedical Materials Research 36 (1997), S. 429-440 
    ISSN: 0021-9304
    Keywords: bone ; interface ; cement line ; bioactive glass ; AW glass ceramic ; hydroxyapatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Rods of three bioactive materials, apatite/wollastonite glass ceramic (AW-GC), bioactive glass (BG), and dense slip-cast hydroxyapatite (HA), were implanted in the femora of 23 Wistar rats for periods of 1-4 weeks. The samples were harvested following vascular perfusion fixation and the femora freeze-fractured for scanning electron microscopy to expose the bone/implant interface. The focus of our observations was when new bone was forming on the implant surfaces irrespective of the implantation period. Scanning microscopy of the hydroxyapatite rods demonstrated that in areas where bone bonding had occurred, the implant surface was composed of globular accretions which fused to form a cement-like matrix to which collagen fibers were attached. Dissolution of individual grains of the implant surface created a roughened surface topography. Such features were not found in the transcortical portions of these implants. Similar globular accretions were also found on the surfaces of bulk AW-GC, although bone apposition was not disrupted by the critical point-drying procedure, and thus the interface was more difficult to image. Nevertheless, the collagen of the bony compartment interdigitated with an interfacial layer which was morphologically similar to that found on HA. The most surface reactive material, BG, demonstrated an interfacial structure where the surface reactive calcium phosphate layer was clearly distinguished from the underlying bulk implant material. However, this layer was separated from the overlying collagen-containing bony compartment by a second, thinner, calcified layer which corresponded to the cement line matrix into which the collagen fibers were inserted. Our results show that the new bone interface formed with these three bioactive materials is morphologically comparable to that of cement lines found naturally in bone-remodeling sites, and that this interfacial layer is formed on the chemically active surface of the biomaterial. The degree to which the cement line matrix interdigitated with the implant was a product of the reactivity of the implant surface. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 36, 429-440, 1997.
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    Journal of Biomedical Materials Research 37 (1997), S. 508-516 
    ISSN: 0021-9304
    Keywords: osteogenesis ; proliferation ; differentiation ; osteoblast ; human ; hydroxyapatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In order to evaluate whether human osteoblastic cells differentiate normally on hydroxyapatite, we have compared the adhesion, proliferation, and differentiation of human trabecular (HT) osteoblastic cells on synthetic-dense hydroxyapatite and on standard plastic culture. We show here that initial HT cell attachment was 4-fold lower on hydroxyapatite than on plastic after 4 h of culture, and that normal cell attachment on hydroxyapatite was restored after 18 h of culture. HT cell proliferation was similar on the two substrates at 2-8 days of culture, but was lower on hydroxyapatite compared to plastic after 15 and 28 days of culture, as evaluated by DNA synthesis or cell number. HT cells cultured on both substrates produced an abundant extracellular matrix which immunostained for Type I collagen. The levels of carboxyterminal propeptide of Type I procollagen (P1CP) in the medium were lower in HT cell cultures on hydroxyapatite than on plastic. In addition, (3H)-proline incorporation into matrix proteins and the mean thickness of matrix layers were 52% and 26% lower, respectively, on hydroxyapatite compared to plastic after 4 weeks of culture, indicating that the total collagenous matrix synthesized by HT cells was lower on hydroxyapatite. However, (3H)-proline and calcium uptake expressed per cell was higher on hydroxyapatite than on plastic. The results show that human osteoblastic cells attach, proliferate, and differentiate on dense hydroxyapatite with a sequence similar to that of plastic. However, the growth of human osteoblastic cells is lower on hydroxyapatite in long-term culture, which results in a reduced amount of extracellular matrix, although matrix production per cell may be increased. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 37, 508-516, 1997.
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    Journal of Biomedical Materials Research 38 (1997), S. 183-190 
    ISSN: 0021-9304
    Keywords: calcification process modeling of heart valves ; kinetics ; hydroxyapatite ; octacalcium phosphate ; calcium phosphates ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A model system was developed for the in vitro quantitative investigation of the calcification process occurring in heart valves. The process of heart valve calcification consists of the formation of calcium phosphates at the heart valve-biological fluid interface. Calcium phosphate deposits may consist of more than one calcium phosphate mineral phase, differing with respect to their physical and chemical properties. The kinetics of the formation of hydroxyapatite, the model inorganic compound for the calcified deposits, was precisely monitored in a reactor containing supersaturated calcium phosphate solutions in which the heart valves were immersed after being treated with glutaraldehyde and mounted on special racks. The precipitation process, accompanied with proton release in the solution, was monitored by a pair of glass-saturated calomel electrodes. Upon initiation of the formation of calcium phosphate deposits, the supersaturation in the working solution was reestablished through the addition of titrant solutions made with the appropriate concentration to compensate for the ions precipitated. With this methodology, not only the rates were measured very precisely but also the nucleation capability of the various substrates could be evaluated. Moreover, it was possible to identify the formation of intermediate calcium phosphate phases formed during the calcification process. Valves previously treated with glutaraldehyde were shown to nucleate octacalcium phosphate, which at lower supersaturations converted to the thermodynamically more stable hydroxyapatite. The rates measured were found to depend on the solution supersaturation, while the apparent order of the precipitation process was found to be 1. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 38: 183-190, 1997
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  • 36
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; fluorapatite ; osteoarthritis ; synoviocytes ; interleukin-1α ; lipoxygenase pathways ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: We investigated the effects of the biomaterials hydroxyapatite (HAP) and fluorapatite (FAP) on cultured human osteoarthritis type B synoviocytes by analyzing interleukin-1α (IL-1α) production and arachidonic acid metabolism via lipoxygenase pathways. A portion of opsonized particles was endocytosed and was found in numerous phagolysosomes in human synoviocyte cytoplasms. The present study demonstrates that HAP and FAP calcined at 700°C induced a decrease in IL-1α production but markedly decreased the synthesis of lipoxygenase products after 1-month incubation with the particles. This model will allow us to study the possible inflammatory response (arachidonic acid metabolism, proinflammatory cytokines) that can be induced by any biomaterials used in orthopedics. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 38: 243-256, 1997
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  • 37
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    Journal of Biomedical Materials Research 37 (1997), S. 457-464 
    ISSN: 0021-9304
    Keywords: biocompatibility ; bone ; calcium phosphate cement ; fast-setting ; hydroxyapatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Fast-setting calcium phosphate cement (FSCPC) is a promising new bioactive cement with a significantly short setting time (approximately 5-6 min) compared to conventional calcium phosphate cement (c-CPC) (30-60 min) at physiologic temperatures. As a result of its ability to set quickly, it is applicable in surgical procedures where fast setting is required. In this study, FSCPC was implanted in rat tibiae to evaluate tissue response and biocompatibility. FSCPC was converted to hydroxyapatite (HAP) in bone faster than c-CPC in the first 6 h. By 24 h, significant amounts of both FSCPC and c-CPC had been converted to HAP. The conversion of FSCPC into HAP further proceeded gradually, reaching 100% within 8 weeks. Infrared spectroscopic analysis disclosed the deposition of B-type carbonate apatite, which is a biological apatite contained in human dentin or bone, on the surface of the FSCPC. Histologically, FSCPC showed a tissue response similar to that of c-CPC. A slight inflammatory reaction was observed in the soft tissue apposed to both cements in the early period, and new bone was formed along the surface of the FSCPC at the adjacent bone. However, no resorption of either cement by osteoclasts or macrophages was observed within 8 weeks. We conclude that FSCPC is superior to c-CPC in clinical applications in oral and maxillofacial, orthopedic, plastic, and reconstructive surgery, since it shows a faster setting time and higher mechanical strength in the early period that are required in these surgical procedures, as well as osteoconductivity and excellent biocompatibility similar to that of c-CPC. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 37, 457-464, 1997.
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  • 38
    ISSN: 0021-9304
    Keywords: calcium phosphate cement ; non-decay type ; putty ; sodium alginate ; hydroxyapatite ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A hydroxyapatite [(HAP) Ca10(PO4)6(OH)2] putty that behaves like a putty or self-curing resin was made by increasing the amount of sodium alginate in non-decay type fast-setting calcium phosphate cement (nd-FSCPC). nd-FSCPC became viscous as the sodium alginate concentration was increased. The best handling properties were obtained when nd-FSCPC contained 8% sodium alginate in its liquid phase. When a 2-kg glass plate was placed on the paste, HAP putty spread to form an area three times that of FSCPC paste. Thus, HAP putty is expected to be easier to use than FSCPC in the filling of bone defects. HAP putty did not decay; in fact, it set within approximately 20 min when immersed in distilled water immediately after mixing. The wet diametral tensile strength value of HAP putty was approximately 12 MPa after 24 h, the same as that for nd-FSCPC containing 0.5% sodium alginate in its liquid phase, or FSCPC that is free from sodium alginate. The elements constituting set HAP putty were examined using powder X-ray diffraction and found to be predominantly apatitic minerals after 24 h. Since the handling properties of a putty or self-curing resinlike cement are very useful in certain surgical procedures, HAP putty made by increasing the sodium alginate concentration in nd-FSCPC is potentially a valuable new biomaterial for use in plastic and reconstructive surgery, as well as oral and maxillofacial surgery. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 36, 393-399, 1997.
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  • 39
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    Journal of Biomedical Materials Research 36 (1997), S. 418-425 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; hydroxyapatite-coated implants ; interface ; bone ; ultrastructure ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The intentions of this study were to characterize the macrosopic, microscopic, and structural aspects of a plasma-sprayed implant and to thoroughly investigate bone tissue response after its implantation in sheep. Therefore, we used scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM, X-ray diffraction, and energy-dispersive X-ray analyses. Assessment of the biomaterial prior to implantation showed a coating with irregular outlines and varying thickness, mainly consisting of hydroxyapatite (HA) covering a rough metallic implant core. Six months after insertion of the HA-coated Ti-6Al-4V implant, neither mechanical failure of the coating-substrate interface nor a significant loss of coating thickness was evident. However, an occasional lack of HA coating and phagocytosis of HA particles were noted. More generally, the implant was surrounded by well-mineralized bone investing the smallest cavities of the plasma-sprayed layer. Newly formed microcrystals with size, shape, and structure similar to those of bone apatite crystals were growing directly at the coating surface. These results suggest that the bone-bonding behavior of the considered grooved implant should provide satisfactory osseointegration and be suitable for fixed prostheses. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 36, 418-425, 1997.
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  • 40
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    Journal of Biomedical Materials Research 38 (1997), S. 129-134 
    ISSN: 0021-9304
    Keywords: blast coating ; sandblast ; hydroxyapatite ; titanium ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: When a titanium plate was blasted with hydroxyapatite [HAP; Ca10-x (HPO4)x(PO4)6-x(OH)2-x] powder at room temperature using an ordinary sandblaster, the surface of the titanium plate was found to be coated with HAP homogeneously and completely. The coated layer was examined with energy dispersive X-ray spectroscopy and X-ray diffraction and was found to be the same as the HAP powder used with respect to composition and crystallographic structure. The coated HAP layer was tightly attached to the surface of the titanium plate, at least at the level of scanning electron microscopy. Interestingly, the HAP particles stuck together at room temperature as if they were sintered. The coating was stable against ultrasonication in water for at least 5 min, and it was difficult to remove by nail scratching. Thus, the bonding strength between the HAP powder and the titanium plate was much higher than that achieved with currently employed room temperature coating processes such as dipping, electrophoretic deposition, and electrochemical deposition. Therefore, the blast coating method is potentially valuable for the fabrication of useful biomaterials for hard tissue replacement. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 38: 129-134, 1997
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  • 41
    ISSN: 0021-9304
    Keywords: bioactive bone cement ; AW glass-ceramic ; hydroxyapatite ; β-TCP ; bioactivity ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Three types of bioactive bone cement (designated AWC, HAC, and TCPC), each consisting of bisphenol-a-glycidyl methacrylate (Bis-GMA)-based resin and a bioactive filler of apatite and wollastonite containing glass-ceramic (AW-GC), sintered hydroxyapatite (HA), or β-tricalcium phosphate (β-TCP) powder were made in order to evaluate the influence of the bioactive filler on the mechanical and biological properties of bone cement. The proportion of filler added to the cements was 70% w/w. The compressive, bending, and tensile strengths and the fracture toughness of AWC were higher than HAC and TCPC under wet conditions. The cements were evaluated in vivo by packing them into the intramedullary canals of rat tibiae. An affinity index that equalled the length of bone in direct apposition to the cement was calculated for each cement and expressed as a percentage of the total length of the cement surface. Histological examination of rat tibiae up to 8 weeks after implantation revealed that AWC had higher bioactivity than HAC and TCPC. New bone had formed along the AWC surface within 2 weeks, and at 4 weeks newly formed bone surrounded the cement surface almost completely. In HAC- and TCPC-implanted tibiae, immature bone had formed directly toward but not along the cement surface at 2 weeks. Observation of cement-bone interfaces showed that AWC had bonded to the bone via a so-called “Ca-P-rich layer”; the cement-bone interface remained stable, and the width of the CA-P-rich layer became thicker with time. On the other hand, in HAC- and TCPC-implanted tibiae, the cement surface fillers were surrounded by new bone and were absorbed gradually to become bone matrix. The cement-bone interfaces went inside the cement with time. Our results indicate that stronger interstitial bonding between the inorganic filler and the organic matrix resin in AWC lead to higher mechanical properties; results also indicate that the more stable cement-bone interface and higher bioactivity of AWC are due to early and uniform apatite formation on the cement surface. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 37, 301-313, 1997.
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  • 42
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    Journal of Biomedical Materials Research 38 (1997), S. 235-241 
    ISSN: 0021-9304
    Keywords: hydroxyapatite ; chitin ; artificial bone ; mechanical properties ; bone composites ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Calcium hydroxyapatite (HA) powder was incorporated into chitin solutions to form an intimate mixture. Upon casting of this mixture into molds of fixed dimensions with subsequent removal of solvent, HAs containing chitin flexible plates were produced. The amount of (HA) was varied from 10 to 50% by mass of HA. The elastic modulus, yield stress, and elongation to fracture, measured at a crosshead speed of 5 mm/min, of these HAs containing chitin flexible plates were evaluated. The amount of HA in the HA incorporated chitin was found to not significantly change the elastic modulus or elongation to fracture. However, a decrease in the maximum tensile stress with an increase in the HA content was found. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 38: 235-241, 1997
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