Surface modification of bioactive glasses and preparation of PDLLA/bioactive glass composite films

In order to improve the homogeneous dispersion of particles in the polymeric matrix, 45S5, mesoporous 58S, and 58S bioactive glasses were surface modified by esterification reactions with dodecyl alcohol at reflux temperature of 260 degrees C (named as m-45S5, m-mesoporous 58S, and m-58S, respectively). The modified particles showed better hydrophobicity and longer time of suspension in organic matrix. The PDLLA/bioactive glass composite films were fabricated using surface modified bioactive glass particles through solvent casting-evaporation method. Surface morphology, mechanical property, and bioactivity were investigated. The results revealed that the inorganic particle distribution and tensile strength of the composite films with modified bioactive glass particles were significantly improved while great bioactive properties were maintained. Scanning electron microscopy (SEM) observation illustrated that the modified bioactive glass particles were homogeneously dispersed in the PDLLA matrix. The maximum tensile strengths of composite films with modified bioactive glass particles were higher than that of composite films with unmodified bioactive glass particles. The bioactivity of the composite films were evaluated by being soaked in the simulated body fluid (SBF) and the SEM observation of the films suggested that the modified composite films were still bioactive in that they could induce the formation of HAp on its surface and the distribution of HAp was even more homogeneous on the film. The results mentioned above indicated that the surface modification of bioactive glasses with dodecyl alcohol was an effective method to prepare PDLLA/bioactive glass composites with enhanced properties. By studying the comparisons of modification effects among the three types of bioactive glasses, we could get the conclusion that the size and morphology of the inorganic particles would greatly affect the modification effects and the properties of composites.     

Fabrication of Poly-(DL-Lactic Acid)--Wollastonite Composite Films with Surface Modified {beta}-CaSiO3 Particles

Bioactive poly-(DL-lactic acid) (PDLLA)-wollastonite composite films are successfully fabricated using surface modified wollastonite (m beta-CaSiO 3) particles through solvent casting-evaporation method. The surface modification of beta-CaSiO3 particles are conducted by reaction of the ceramic particles with dodecyl alcohol. Surface morphology, tensile strength, and bioactivity of the composite films are investigated. The results show that the particle distribution and tensile strength of the composite films with modified beta-CaSiO3 particles are significantly improved while the bioactivity is retained. As a result, the maximum tensile strength is enhanced 52.2% when compared with the PDLLA-beta-CaSiO3 composite films prepared using unmodified beta-CaSiO3 particles when the inorganic filler content is 15 wt%. Scanning electron microscopy (SEM) observation suggests that the modified m beta-CaSiO3 particles are homogeneously dispersed in the PDLLA matrix. The bioactivity of the composite films is evaluated by soaking in a simulated body fluid (SBF) and the result suggests that the modified composite film is still bioactive and can induce the formation of HAp on its surface after the immersion in SBF, despite the bonded dodecyl alkyl on the surface of the inorganic particles. All these results imply that the surface modification of beta-CaSiO3 with dodecyl alcohol is an effective approach to prepare PDLLA-beta-CaSiO3 composite with improved properties.     

Nanolayering of phosphoric acid ester monomer on enamel and dentin

Following the "adhesion-decalcification" concept, specific functional monomers possess the capacity to primary chemically interact with hydroxyapatite (HAp). Such ionic bonding with synthetic HAp has been demonstrated for 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP), manifest as self-assembled "nanolayering". In continuation of that basic research this study aimed to explore whether nanolayering also occurs on enamel and dentin when a 10-MDP primer is applied following a common clinical application protocol. Therefore, the interaction of an experimental 10-MDP primer and a control, commercially available, 10-MDP-based primer (Clearfil SE Bond primer (C-SE), Kuraray) with enamel and dentin was characterized by X-ray diffraction (XRD), complemented with transmission electron microscopy interfacial ultrastructural data upon their reaction with enamel and dentin. In addition, XRD was used to study the effect of the concentration of 10-MDP on nanolayering on dentin. Finally, the stability of the nanolayers was determined by measuring the bond strength to enamel and dentin when a photoinitiator was added to the experimental primer or when interfacial polymerization depended solely on the photoinitiator supplied with the subsequently applied adhesive resin. XRD confirmed nanolayering on enamel and dentin, which was significantly greater on dentin than on enamel, and also when the surface was actively rubbed with the primer. Nanolayering was also proportional to the concentration of 10-MDP in the primer. Finally, the experimental primer needed the photoinitiator to obtain a tensile bond strength to dentin comparable with that of the control C-SE primer (which also contains a photoinitiator), but not when bonded to enamel. It is concluded that self-assembled nanolayering occurs on enamel and dentin, even when following a clinically used application protocol. The lower bonding effectiveness of mild self-etch adhesives to enamel should be ascribed in part to a lower chemical reactivity (nanolayering) with enamel HAp.     

Preparation and characterization of keratin-chitosan composite film.

Keratin-chitosan composite film was prepared by casting the mixed solution of both biopolymers in 75% acetic acid. Although keratin film without any additive is very fragile, 10-30 wt% of chitosan addition gave strong and flexible film (ultimate strength: 27-34 MPa, ultimate elongation: 4-9%). Glycerol (20 wt%) also afforded flexibility to keratin film (ultimate strength: 1 MPa, ultimate elongation: 28%). Further addition of chitosan to glycerol-containing keratin film increased the ultimate strength to 9-14 MPa but gave little effect on ultimate elongation. These data suggest that mechanical properties of keratin film are adjustable by appropriately adding chitosan and glycerol. Waterproof characteristics such as swelling behavior and mechanical properties after swelling were much ameliorated for the composite film compared with keratin and chitosan films, respectively. Furthermore, keratin-chitosan composite film as well as chitosan film decreased bacteria number when the bacteria suspension was treated with a film owing to the irreversible adsorption of bacteria onto the film. The composite film as well as keratin and chitosan films supported fibroblast attachment and proliferation, demonstrating to be a good substrate for mammalian cell culture.     

The fabrication and biochemical evaluation of alumina reinforced calcium phosphate porous implants

Alumina reinforced calcium phosphate porous implants were manufactured to improve the mechanical strength while maintaining the bioactivity of calcium phosphate ceramics. The alumina porous bodies, which provided the mechanical strength, were fabricated by a polyurethane sponge method and multiple coating techniques resulted in the porous bodies with a 90-75% porosity and a compressive strength of up to approximately 6MPa. The coating of hydroxyapatite (HAp) or tricalcium phosphate (beta-TCP) was performed by dipping the alumina porous bodies into calcium phosphate ceramic slurries and sintering the specimens. The fairly strong bonding between the HAp or TCP coating layer and the alumina substrate was obtained by repeating the coating and sintering processes. The biochemical evaluations of the porous implants were conducted by in vitro and in vivo tests. For in vitro test, the implants were immersed in Ringer's solution and the release of Ca and P ions were detected and compared with those of calcium phosphate powders. For in vivo test, the porous bodies were implanted into mixed breed dogs and bone mineral density measurements and histological studies were conducted. The alumina reinforced HAp porous implants had a higher strength than the HAp porous implants and exhibited a similar bioactivity and osteoconduction property to the HAp porous implants.     

Effect of elapsed time following bleaching on the shear bond strength of composite resin to enamel

The purpose of this study was to investigate the effect of post-treatment time on the shear bond strength of composite resin to enamel after bleaching with 10% carbamide peroxide (CP) and 35% hydrogen peroxide (HP) bleaching systems. One hundred and thirty-five flattened labial enamel surfaces obtained from human mandibular incisors were divided into two bleaching groups of 10% CP (n = 60) and 35% HP (n = 60) and a control group (n = 15). Specimens in the control group (group 1) were not bleached. Each bleaching group was then divided into four subgroups (n = 15). For both CP and HP groups, group 2 consisted of specimens bonded immediately after bleaching. In groups 3, 4, and 5, specimens were immersed in artificial saliva for 24 h, 1 week, or 2 weeks after bleaching, respectively. After the specimens were bonded with Clearfil SE Bond and Clearfil ST, they were tested in shear until failure. For both CP and HP groups, shear bond strength of composite resin to enamel that was bonded immediately after bleaching was significantly lower than that of unbleached enamel (p < 0.05). However, in CP group restored after 24 h, the bond strength returned to values close to those of nonbleached enamel (p > 0.05). It took 1 week to return to conditions that lead to control bond values for HP bleaching applications (p > 0.05). The results of this study proved that immediate bonding of composite to enamel bleached with 10% CP and 35% HP gels result in a significant decrease in shear bond strength. It is advisable that composite resin application onto bleached enamel surfaces should be delayed at least 24 h for 10% CP and 1 week for 35% HP.     

Injectable polydimethylsiloxane-hydroxyapatite composite cement

An injectable polydimethylsiloxane/hydroxyapatite (PDMS/HAp) composite cement was synthesised using linear PDMS and HAp (particles of about 100 nm in size) of different mass fractions. The effect of HAp mass fraction (5-60 mass%) on the hardness of PDMS/HAp composite cement was investigated. The hardness achieved is 25-49 degrees ShA. Differential scanning calorimetry (DSC) was used to study the cross-linking process and the influence of HAp on the temperature and duration of PDMS/HAp cross-linking. The microstructure of composite cement surfaces after 10 days in vivo tests was observed by scanning electron microscopy (SEM). The presence of well-adhered macrophages, fibroblasts and monocytes was found on the implant surface upon its extraction from the organism.     

Increase in cell adhesiveness on a poly(ethylene terephthalate) fabric by sintered hydroxyapatite nanocrystal coating in the development of an artificial blood vessel

Nano-scaled sintered hydroxyapatite (HAp) crystals were covalently linked onto a poly(ethylene terephthalate) (PET) fabric substrate chemically modified by graft polymerization with gamma-methacryloxypropyl triethoxysilane (MPTS) for development of an artificial blood vessel. The weight gain of graft polymerization with poly(MPTS) on PET in benzyl alcohol containing H2O2 as an initiator increased as increasing the reaction time and finally reached a plateau value of about 3.5 wt%. The surface characterization of surface modification with poly(MPTS)-grafting was conducted by x-ray photoelectron spectroscopy. HAp nanocrystals of approximately 50 nm in diameter, monodispersed in pure ethanol, were coupled with alkoxysilyl groups of the poly(MPTS)-grafted PET substrate. The HAp nanocrystals were uniformly and strongly coated on the surface of the PET fabrics, although HAp particles adsorbed physically on the original PET without poly(MPTS) grafting were almost removed by ultrasonic wave treatment. More human umbilical vein endothelial cells adhered to the HAp/PET composite fabric compared with original PET after only 4 hours of initial incubation, and the same was observed on the collagen-coated PET. The coating of sintered HAp nanocrystals imparted bioactivity to the polyester substrate, which is a widely used biomedical polymer, without a coating of adhesion proteins derived from animals, such as collagen or gelatin. A prototype of an artificial blood vessel was finally fabricated by use of HAp/PET composite.     

Effect of oxygen inhibition on composite repair strength over time

The study was aimed at examining whether an oxygen inhibition layer is required for bonding a repairing to a pre-existing composite, and to determine the time required for free radicals within a composite substrate to decay to the extent that the composite repair strength drops significantly. Ten slabs of Gradia Direct Anterior (GC Corp.) were divided into (1) control group: an interfacial oxygen inhibition layer was created by applying and light-curing two layers of bonding resin (D/E Resin, Bisco) to the slabs surface in atmospheric air; (2) experimental group: the absence of an interfacial oxygen inhibition layer was obtained by light-curing the second bonding resin layer in a nitrogen atmosphere. After 1 and 2 h, 1, 14, and 30 days of air storage, a composite repair was layered over the bonding resin. Microtensile bond strengths were measured and statistically analyzed. The curing atmosphere was not a significant factor for bond strength (p = 0.82), and time and curing atmosphere-time interaction were significant (p < 0.001). The 30 day-strengths were the lowest (p < 0.05). An oxygen-inhibited layer is not initially required for bonding to resin composite, and it takes more than 14 days before the bond strength between a pre-existing and a fresh composite drops.     

Improved photochemical bonding of composites to dentin using 4-methacryloxyethyl trimellitate anhydride

The main objective was to evaluate the use of 4-methacryloxyethyl trimellitate anhydride (4-META) to improve bonding of composite materials to dentin. Bowen's resin, containing camphoroquinone, was polymerized by exposure to visible light. In composites, made with a silanated silicate, inclusion of 4-META (3%) had little effect in increasing mechanical strength or adhesion to bovine teeth. However, direct application of 4-META via acetone solution was found to be an effective way of increasing tensile adhesive strength; by 240% to dentin (to 7.2 MPa) and by 160% to enamel (to 10.8 MPa). Applying the experience mentioned above, 4-META was used to bond a proprietary photocuring microfilled composite material to Class V cavities in freshly extracted human teeth. After thermal cycling between water baths held at 5 degrees C and 60 degrees C, all dentin restorations without 4-META failed, as judged by marginal leakage of a dyestuff. In contrast, using 4-META there was no leakage in 9 out of 10 cases. In restorations involving enamel, 4-META failed to prevent marginal leakage at the enamel margins but did prevent penetration along the dentin/composite interface. It is concluded that 4-META shows great promise for preventing marginal leakage at dentin/composite interfaces.     

Evaluating interface strength of calcium phosphate sol-gel-derived thin films to Ti6Al4V substrate

The interface shear strength of Ca-P thin films applied to Ti6Al4V substrates have been evaluated in this study using a substrate straining method--a shear lag model. The Ca-P films were synthesized using sol-gel methods from either an inorganic or organic precursor solution. Strong interface bonding was demonstrated for both film types. The films were identified as non-stoichiometric hydroxyapatite but with different Ca/P ratios. The Ca-P films were 1-1.5 microm thick and testing and analysis using the shear lag approach revealed a shear strength of approximately 347 and 280 MPa for Inorganic and Organic Route-formed films, respectively. Overall, the exceptional mechanical properties of Ca-P/Ti6Al4V system along with the inherent advantages of sol-gel processing support continued studies to utilize this technology for bone-interfacing implant surface modification.     

Rational design of a high-strength bone scaffold platform based on in situ hybridization of bacterial cellulose/nano-hydroxyapatite framework and silk fibroin reinforcing phase

Bacterial cellulose/hydroxyapatite (BC/HAp) composite had favourable bioaffinity but its poor mechanical strength limited its widespread applications in bone tissue engineering (BTE). Silk fibroin, which possesses special crystalline structure, has been widely used as organic reinforcing material, and different SFs have different amino acid sequences, which exhibit different bioaffinity and mechanical properties. In this regard, bacterial cellulose-Antheraea yamamai silk fibroin/hydroxyapatite (BC-AYSF/HAp), bacterial cellulose-Bombyx mori silk fibroin/hydroxyapatite (BC-BMSF/HAp), and BC/HAp nano-composites were synthesized via a novel in situ hybridization method. Compared with BC/HAp and BC-BMSF/HAp, the BC-AYSF/HAp exhibited better interpenetration, which may benefit for the transportation of nutrients and wastes, the adhesion of cells as well. Additionally, the BC-AYSF/HAp also presented superior thermal stability than the other two composites revealed by differential thermal analysis (DTA) and thermogravimetric analysis (TGA). Compression testing indicated that the mechanical strength of BC-BMSF/HAp was greatly reinforced compared with BC/HAp and was even a little higher than that of BC-AYSF/HAp. Tensile testing showed that BC-AYSF/HAp possesses extraordinary mechanical properties with a higher elastic modulus at low strain and higher fracture strength simultaneously than the other two composites. In vitro cell culture exhibited that MC3T3-E1 cells on the BC-AYSF/HAp membrane took on higher proliferative potential than those on the BC-BMSF/HAp membrane. These results suggested that compared with BC-BMSF/HAp, the BC-AYSF/HAp composite was more appropriate as an ideal bone scaffold platform or biomedical membrane to be used in BTE.     

Fabrication and characterization of polysulfone-dicalcium silicate composite films

Polysulfone (PSU) composite films filled with Beta-dicalcium silicate (Beta-Ca(2)SiO(4)) particles are prepared by the solvent casting-evaporation method. The surface morphologies and mechanical properties of the films are determined. The bioactivity of the composite films is evaluated by soaking them in simulated body fluid (SBF) and the results show that the composites are bioactive as they induce the formation of hydroxyapatite (HAp) on the surface of the composite films. The measurement of the water contact angles suggests that the incorporation of Beta-Ca(2)SiO(4) particles into PSU matrix can improve the hydrophilicity of the composite. PSU composite films filled with modified Beta-dicalcium silicate (Beta-mCa(2)SiO(4)) particles are also prepared after Beta-Ca(2)SiO(4) particles are treated with dodecyl alcohol through surface esterification reactions. The infrared spectra of the Beta-mCa(2)SiO(4) particles before and after aging in water indicate that the surface modification is reversible. The scanning electron microscope (SEM) images (micrographs) of both composites show that the dispersion of inorganic particles in the polymer matrix improves after surface modification. The PSU-Beta-mCa(2)SiO(4) composite is still bioactive and exhibits the same water contact angle after aging in water as compared to that of the PSU-Beta-Ca(2)SiO(4) composite. All these results suggest that the incorporation of Beta-Ca(2)SiO(4) particles is a useful method to prepare composites with improved bioactivity and hydrophilicity, and the surface modification of Beta-Ca(2)SiO(4) particles can improve the dispersion while retaining the bioactivity and hydrophilicity.     

Effect of temperature and ageing on the mechanical properties of dental polymeric composite materials

Evaluation of the mechanical properties of some dental composite materials, Compact, Finesse and Prisma-Fil based on bisphenol glycidyl methacrylate resin was undertaken by applying compression, tension and hardness tests. The effects of temperature and ageing times on these properties were studied. There was a marked increase in the mechanical properties (compressive strength, diametral tensile strength, compressive elastic modulus and hardness) for all the investigated composites with increase of both temperature and time. This was explained in terms of the influence of temperature on the polymerization rate of the materials. The improvement in the mechanical properties of the samples, kept at 37 degrees C, was attributed to further and continued polymerization of the polymer content of their resin system. Such mechanical improvement was verified by the regression equation of linearity versus both temperature and time.     

Effects of MgO-CaO-P2O5-Na2O-based additives on mechanical and biological properties of hydroxyapatite

In this research, we improved densification, hardness, and compression strength of synthetic hydroxyapatite (HAp) ceramics by introducing small quantities of MgO-CaO-P(2)O(5)-Na(2)O-based sintering additives. Biological properties of HAp were not altered by this procedure. Phase analyses were performed by using a Philips Xpert fully automated diffractometer with Co K-alpha radiation to understand the influence of additives on phase purity in the final products. All compositions were characterized at green and sintered densities to understand the influence of additives on densification. Some of the compositions showed >40% increase in Vickers microhardness compared with pure HAp processed under the same conditions. Improvement in compression strength was also detected in some compositions. In vitro biological testing used a modified human osteoblast cell line to test biocompatibility, cell attachment, and cell proliferation. All these compositions were nontoxic and biocompatible. Our results indicate that MgO-CaO-P(2)O(5)-Na(2)O-based sintering additives can be used to improve both mechanical and biological properties of HAp ceramics.     

Bioadhesion of gelatin films crosslinked with glutaraldehyde.

The present study was carried out in an attempt to make a gelatin film strongly bioadhesive by introducing free dangling aldehyde groups. When gelatin films were treated with 0.5M of glutaraldehyde (GA) solution at 60 degrees C, free aldehyde groups (up to 150 micromol/g) were introduced in the film. The bonding strength of GA-crosslinked gelatin films (GA gelatin films) with biological tissue was assessed using porcine skins. It was found that bonding strength increased with increasing aldehyde content in the film. The GA gelatin films had bonding strength as high as 250 gf/cm2 whereas the native gelatin film (before GA treatment) showed bonding strength of 40 gf/cm2. When the aldehyde groups introduced in the gelatin films were quenched with glycine or reduced by NaBH4, the films no longer demonstrated such high bonding strength. These facts suggest that a Schiff base was formed between the free dangling aldehyde in the GA gelatin films and the amino groups of the natural tissue, which strongly contributed to a marked bioadhesion.Copyright 1999 John Wiley & Sons, Inc.     

Self-organization mechanism in a bone-like hydroxyapatite/collagen nanocomposite synthesized in vitro and its biological reaction in vivo

When bone is lost due to injury and/or illness, the defects are generally filled with natural bone because artificial bone materials have problems of bioaffinity. However, natural bone also has supply and infection problems. If an artificial material has the same biological properties as bone, it can replace natural bone for grafting. We synthesized a hydroxyapaite (HAp) and collagen (Col) composite by a simultaneous titration coprecipitation method using Ca(OH)2, H3PO4 and porcine atelocollagen as starting materials. The composite obtained showed a self-organized nanostructure similar to bone assembled by the chemical interaction between HAp and Col. The consolidated composite by a cold isostatic pressure of 200 MPa indicated a quarter of the mechanical strength of bone. It also indicated the same biological properties as grafted bone: The material was resorbed by phagocytosis of osteoclast-like cells and conducted osteoblasts to form new bone in the surrounding area. This HAp/Col composite having similar nanostructure and composition can replace autologous bone grafts.     

Whisker-reinforced bioactive composites containing calcium phosphate cement fillers: effects of filler ratio and surface treatments on mechanical properties

Calcium phosphate cement (CPC) sets to form microporous solid hydroxyapatite with excellent osteoconductivity, but its brittleness and low strength prohibit use in stress-bearing locations. The aim of this study was to incorporate prehardened CPC particles and ceramic whiskers in a resin matrix to improve the strength and fracture resistance, and to investigate the effects of key microstructural variables on composite mechanical properties. Two types of whiskers were used: silicon nitride, and silicon carbide. The whiskers were surface-treated by fusing with silica and by silanization. The CPC particle fillers were either silanized or not silanized. Seven mass ratios of whisker-silica/CPC were mixed: 0:1 (no whisker-silica), 1:5, 1:2, 1:1, 2:1, 5:1, and 1:0 (no CPC). Each powder was blended with a bisphenol-a-glycidyl methacrylate-based resin to harden in 2 x 2 x 25 mm molds by two-part chemical curing. The specimens were tested in three-point flexure to measure strength, work-of-fracture (toughness), and elastic modulus. Two-way analysis of variance was used to analyze the data, and scanning electron microscopy was used to examine specimen fracture surfaces. The whisker-silica/CPC ratio had significant effects on composite properties (p < 0.001). When this ratio was increased from 0:1 to 1:0, the strength was increased by about three times, work-of-fracture by five times, and modulus by two times. Whisker surface treatments and CPC filler silanization also had significant effects (p < 0.001) on composite properties. Scanning electron microscopy revealed rough fracture surfaces for the whisker composites with steps and whisker pullout. Resin remnants were observed on the surfaces of the pulled-out whiskers, indicating strong whisker-matrix bonding. In conclusion, incorporating highly osteoconductive CPC fillers and ceramic whiskers yielded composites with substantially improved mechanical properties compared with composites filled with CPC particles without whiskers. The composite properties were determined by whisker-to-CPC ratio and filler surface treatments.     

A multiscale modeling approach to scaffold design and property prediction

The optimum scaffold architecture for bone tissue regeneration is a porous structure with a narrow range of pore sizes, pore density, and a high degree of interconnectivity among pores. To achieve such a design, the microstructure of the scaffold material must be optimized in order to satisfy both biological and mechanical function requirements. In this paper, we present a multiscale modeling approach for designing a scaffold with an optimized porosity and mechanical properties made from a two-phase composite of spherical hydroxyapatite (HAp) particles embedded in a collagen matrix. In particular, first-principles computation is used to calculate the elastic properties and theoretical strengths of nanoscaled HAp particles. The constitutive properties of the HAp/collagen composites are subsequently computed as a function of HAp content via FEM-based micromechanical modeling. The constitutive relations of the composite are then utilized to optimize the mechanical properties of a three-dimensional scaffold for either cortical or cancellous bone by varying the pore size, pore density and volume fractions of HAp in the composite. For the pore size, pore density, volume fractions of HAp considered, the scaffold can be designed to match the mechanical properties of cancellous bone, but not those of cortical bone. The optimized scaffold is one with a pore diameter of 1000 μm, a channel diameter of 100 μm, 27% pore density and at least 20% HAp by volume.     

Development and evaluation of cross-linked collagen-hydroxyapatite scaffolds for tissue engineering

This study examines the tissue engineering potential of type I collagen cross-linked in the presence of hydroxyapatite (HAp). Scaffolds were prepared by controlled freezing followed by lyophilization of composite mixtures of collagen and HAp in acetic acid, followed by cross-linking with 0.3% glutaraldehyde. Scaffolds of three ratios were prepared, corresponding to collagen/HAp ratios of 1:2, 1:4, and 1:6. The scaffolds were evaluated for their microstructure, chemical and physical properties, swelling behavior, mechanical strength, biodegradability hemocompatability, cytocompatibility, and histopathology following subcutaneous implantation in Sprague Dawley rats. The collagen/HAp matrices showed a smaller pore size of 10–40?μm compared to 50–100?μm for pure collagen scaffolds. Pure collagen showed a mechanical strength of 0.25?MPa, and the value almost doubled for cross-linked composites with collagen/HAp ratio 1:6. The improvement in mechanical strength corresponded to a decrease in swelling and enzymatic degradation (measured by resistance to collagenases). FTIR spectra results in conjunction with scanning electron micrographs showed that cross-linking in the presence of HAp did not significantly alter the structure of collagen. MTT assay and calcein AM staining revealed prominent and healthy growth of mesenchymal stem cells in both the pure collagen as well as collagen:HAp composites of ratio 1:2. In vivo implantation in Sprague Dawley rats showed an initial acute inflammatory response during days 3 and 7, followed by a chronic, macrophage-mediated inflammatory response on days 14 and 28. Overall, a cross-linked collagen/HAp composite scaffold of ratio 1:2 was identified as having potential for further development in tissue engineering.