Collagen I-coated titanium surfaces: mesenchymal cell adhesion and in vivo evaluation in trabecular bone implants

The goal of the study was the evaluation of the effect of modification of titanium implants by acrylic acid surface grafting-collagen I coupling. Tests were performed on titanium samples treated by galvanostatic anodization to create a porous surface topography. Surface characterization by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) confirms the biochemical modification of the surface and shows a surface topography characterized by pores mostly below 1 mum diameter. In vitro evaluation involving human mesenchymal cells shows enhanced cell growth on collagen coated surfaces as compared to titanium ones. Four weeks in vivo evaluation of implants in rabbit femur trabecular bone shows improvements of bone-to-implant contact, while improvement of bone ingrowth is slightly not significant (p = 0.056), when compared to the control. Overall, these data indicate that integration in trabecular, or cancellous, bone can be enhanced by the surface collagen layer, confirming previous findings obtained by modification of machined surfaces by the same approach in cortical bone implants.     

Bone response to a novel highly porous surface in a canine implantable chamber

Long-term survival of uncemented hip components is dependent upon successful biological fixation. This study examined a new prosthetic surface treatment consisting of a highly porous open structure of commercially pure titanium, Tritanium Dimensionalized Metal; its overall porosity is approximately 65-70%. With the use of an implantable chamber in dogs, the effects of this treatment on bone ingrowth and strength of attachment were compared to both titanium (overall porosity of 30-35%) and cobalt chrome beads (overall porosity of 35-40%), with and without hydroxyapatite coating. At 6 and 12 weeks, chambers were explanted and specimens underwent high-resolution radiographic imaging and mechanical testing. At 12 weeks, Tritanium surfaces had greater bone penetration and tensile strength than remaining surface types. Over 40% of the Tritanium specimens had a tensile strength greater than 500 N, exceeding the testing capability of the servohydraulic equipment. The highly porous Tritanium surfaces allow for a far greater amount of bone ingrowth than beaded surfaces, and may create a geometry that enhances mechanical strength. Tritanium Dimensionalized Metal surface treatment may result in a clinically valuable implant fixation surface to induce rapid ingrowth and a strong bone-implant interface, contributing to increased implant survivorship.     

Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength.

The effect of a plasma-sprayed hydroxylapatite (HA) coating on the degree of bone ingrowth and interface shear attachment strength was investigated using a canine femoral transcortical implant model. Cylindrical implants were fabricated by sintering spherical Co-Cr-Mo particles 500-710 microns in diameter; the nominal implant dimensions were 5.95 +/- 0.05 mm diameter by 18 mm in length. One half of each implant was coated with hydroxylapatite, 25-30 microns in thickness, by a plasma-spray technique. Using strict aseptic technique, the implants were placed through both femoral cortices into defects approximately 0.05 mm undersized. After 2, 4, 6, 8, 12, 18, 26, and 52 weeks, the implants were harvested and subjected to mechanical pullout testing and undecalcified histologic evaluation. The application of the HA coating to porous implants enhanced both the amount of bone ingrowth and the interface attachment strength at all time periods. These differences were statistically significant for the percent of bone ingrowth at the 4-, 6-, 12-, 18-, 26-, and 52-week time periods, and interface shear strength values were significantly different at the 6-, 8-, 12-, 18-, and 26-week time periods. The rate of development of interface strength and bone ingrowth was also more rapid for the HA-coated implants. No evidence of any disruption, mechanical failure, or biologic resorption of the HA coating was observed. The results of the present study--demonstrating a beneficial effect of the HA coating at all time periods--are believed to be due to the use of paired comparisons, which allow assessment of subtle differences that might otherwise have been obscured by normal biological variability.     

Interface shear strength and fracture behaviour of porous glass-fibre-reinforced composite implant and bone model material

Glass-fibre-reinforced composites (FRCs) are under current investigation to serve as durable bone substitute materials in load-bearing orthopaedic implants and bone implants in the head and neck area. The present form of biocompatible FRCs consist of non-woven E-glass-fibre tissues impregnated with varying amounts of a non-resorbable photopolymerisable bifunctional polymer resin with equal portions of both bis-phenyl-A-glycidyl dimethacrylate (BisGMA) and triethyleneglycol dimethacrylate (TEGDMA). FRCs with a total porosity of 10-70 vol% were prepared, more than 90 vol% of which being functional (open pores), and the rest closed. The pore sizes were greater than 100?μm. In the present study, the push-out test was chosen to analyse the shear strength of the interface between mechanically interlocked gypsum and a porous FRC implant structure. Gypsum was used as a substitute material for natural bone. The simulative in vitro experiments revealed a significant rise of push-out forces to the twofold level of 1147 ±?271?N for an increase in total FRC porosity of 43%. Pins, intended to model the initial mechanical implant fixation, did not affect the measured shear strength of the gypsum-FRC interface, but led to slightly more cohesive fracture modes. Fractures always occurred inside the gypsum, it having lower compressive strength than the porous FRC structures. Therefore, the largest loads were restricted by the brittleness of the gypsum. Increases of the FRC implant porosity tended to lead to more cohesive fracture modes and higher interfacial fracture toughness. Statistical differences were confirmed using the Kruskal-Wallis test. The differences between the modelled configuration showing gypsum penetration into all open pores and the real clinical situation with gradual bone ingrowth has to be considered.     

Bone response to endosseous titanium implants surface-modified by blasting and chemical treatment: a histomorphometric study in the rabbit femur

This study evaluated the effects of the addition of oxide structure with submicron-scale porous morphology on the periimplant bone response around titanium (Ti) implants with microroughened surfaces. Hydroxyapatite-blasted Ti implants with (experimental) and without (control) a porous oxide structure produced by chemical treatment were investigated in a rabbit femur model. Surface characterizations and in vivo bone response at 4 and 8 weeks after implantation were compared. The experimental implants had submicron-scale porous surface structure consisted of anatase and rutile phase, and the original R(a) values produced by blasting were preserved. The histomorphometric evaluation demonstrated statistically significantly increased bone-to-implant contact (BIC) for experimental implants, both in the three best consecutive threads (p < 0.01) and all threads (p < 0.05) at 4 weeks. There was no remarkable difference in the BIC% or bone area percentage between the two groups at 8 weeks. The porous Ti oxide surface enhanced periimplant bone formation around the Ti implants with microroughened surfaces at the early healing stage. Based on the results of this study, the addition of crystalline Ti oxide surface with submicron-sized porous morphology produced by chemical treatment may be an effective approach for enhancing the osseointegration of Ti implants with microroughened surfaces by increasing early bone-implant contact.     

In vivo histological response to anodized and anodized/hydrothermally treated titanium implants

In the study, characterization of the anodized titanium surface was performed. In addition, histological evaluation and interfacial strength at the bone-implant interface of the characterized surfaces were then evaluated with the use of a rabbit model at 6 and 12 weeks after implantation. Surface treatments consisted of either anodization or anodization followed by hydrothermal treatments. Nontreated titanium surfaces were used as controls in this study. Using scanning-electron microscopy, porous oxide layers were observed on surfaces of anodized titanium implants, whereas porous oxide layers and HA needles were observed on anodized titanium implants following hydrothermal treatments. X-ray diffraction analysis showed the oxide layers were consisted mainly of anatase and a little of rutile. By the hydrothermal treatment on the anodizing surface, HA peaks, as well as the peaks of anatase and trace amounts of rutile peaks were observed. In EPMA analysis, the Ca/P ratio for the anodic oxide was 1.54 for anodized surfaces, whereas the Ca/P ratios for HA needles and the anodic oxide were 1.64 and 0.57, respectively, for anodized surfaces following hydrothermal treatments. Although no significant difference was observed for the percent bone contact on all implants evaluated in the in vivo study, the removal torque strength was significantly higher for anodized implants (48.02+/-5.92 N/cm) than the untreated implants (controls) (27.83+/-1.78 N/cm) at 6 weeks after implantation. As such, it was concluded that the surface anodized implants resulted in a high interfacial strength at an early implantation period as compared to the nontreated titanium implants.     

The structure of the bond between bone and porous silicon-substituted hydroxyapatite bioceramic implants

The significance of micrometer-sized strut porosity in promoting bone ingrowth into porous hydroxyapatite (HA) scaffolds has only recently been noted. In this study, silicon-substituted HA (0.8 wt % Si-HA) with approximately 8.5% of the total porosity present as microporosity within the struts of the implant was prepared for high-resolution transmission electron microscopy (HR-TEM) via both ultramicrotomy and focused ion beam milling. Between the struts of the porous Si-HA, pores with varying shapes and sizes (1-10 microm in diameter) were characterized. Within the struts, the Si-HA contained features such as grain boundaries and triple-junction grain boundaries. Bone ingrowth and dissolution from a Si-HA implant were studied using HR-TEM after 6 weeks in vivo. Minor local dissolution occurred within several pores within the struts. Organized, mineralized collagen fibrils had grown into the strut porosity at the interface between the porous Si-HA implant and the surface of the surrounding bone. In comparison, deeper within the implant, disorganized and poorly mineralized fibers were observed within the strut porosity. These findings provide valuable insight into the development of bone around porous Si-HA implants.     

The effect of sol-gel-formed calcium phosphate coatings on bone ingrowth and osteoconductivity of porous-surfaced Ti alloy implants

Ti-6Al-4V implants formed with a sintered porous surface for implant fixation by bone ingrowth were prepared with or without the addition of a thin surface layer of calcium phosphate (Ca-P) formed using a sol-gel coating technique over the porous surface. The implants were placed transversely across the tibiae of 17 rabbits. Implanted sites were allowed to heal for 2 weeks, after which specimens were retrieved for morphometric assessment using backscattered scanning electron microscopy and quantitative image analysis. Bone formation along the porous-structured implant surface, was measured in relation to the medial and lateral cortices as an indication of implant surface osteoconductivity. The Absolute Contact Length measurements of endosteal bone growth along the porous-surfaced zone were greater with the Ca-P-coated implants compared to the non-Ca-P-coated implants. The Ca-P-coated implants also displayed a trend towards a significant increase in the area of bone ingrowth (Bone Ingrowth Fraction). Finally, there was significantly greater bone-to-implant contact within the sinter neck regions of the Ca-P-coated implants.     

Bioactive macroporous titanium surface layer on titanium substrate

A macroporous titanium surface layer is often formed on titanium and titanium alloy implants for morphological fixation of the implants to bone via bony ingrowth into the porous structure. The surface of titanium metal was recently shown to become highly bioactive by being subjected to 5.0 M-NaOH treatment at 60 degrees C for 24 h and subsequent heat treatment at 600 degrees C for 1 h. In the present study, the NaOH and heat treatments were applied to a macroporous titanium surface layer formed on titanium substrate by a plasma spraying method. The NaOH and heat treatments produced an uniform amorphous sodium titanate layer on the surface of the porous titanium. The sodium titanate induced a bonelike apatite formation in simulated body fluid at an early soaking period, whereby the apatite layer grew uniformly along the surface and cross-sectional macrotextures of the porous titanium. This indicates that the NaOH and heat treatments lead to a bioactive macroporous titanium surface layer on titanium substrate. Such a bioactive macroporous layer on an implant is expected not only to enhance bony ingrowth into the porous structure, but also to provide a chemical integration with bone via apatite formation on its surface in the body.     

Biomechanical evaluation of the interfacial strength of a chemically modified sandblasted and acid-etched titanium surface

The functional capacity of osseointegrated dental implants to bear load is largely dependent on the quality of the interface between the bone and implant. Sandblasted and acid-etched (SLA) surfaces have been previously shown to enhance bone apposition. In this study, the SLA has been compared with a chemically modified SLA (modSLA) surface. The increased wettability of the modSLA surface in a protein solution was verified by dynamic contact angle analysis. Using a well-established animal model with a split-mouth experimental design, implant removal torque testing was performed to determine the biomechanical properties of the bone-implant interface. All implants had an identical cylindrical shape with a standard thread configuration. Removal torque testing was performed after 2, 4, and 8 weeks of bone healing (n = 9 animals per healing period, three implants per surface type per animal) to evaluate the interfacial shear strength of each surface type. Results showed that the modSLA surface was more effective in enhancing the interfacial shear strength of implants in comparison with the conventional SLA surface during early stages of bone healing. Removal torque values of the modSLA-surfaced implants were 8-21% higher than those of the SLA implants (p = 0.003). The mean removal torque values for the modSLA implants were 1.485 N m at 2 weeks, 1.709 N m at 4 weeks, and 1.345 N m at 8 weeks; and correspondingly, 1.231 N m, 1.585 N m, and 1.143 N m for the SLA implants. The bone-implant interfacial stiffness calculated from the torque-rotation curve was on average 9-14% higher for the modSLA implants when compared with the SLA implants (p = 0.038). It can be concluded that the modSLA surface achieves a better bone anchorage during early stages of bone healing than the SLA surface; chemical modification of the standard SLA surface likely enhances bone apposition and this has a beneficial effect on the interfacial shear strength.     

Bone growth in rapid prototyped porous titanium implants

Two porous titanium implants with a pore size diameter of 800 and 1200 microm (Ti800 and Ti1200) and an interconnected network were manufactured using rapid prototyping. Their dimensions and structure matched those of the computer assisted design. The porosity of the implants was around 60%. Their compressive strength and Young's modulus were around 80 MPa and 2.7 GPa, respectively. These values are comparable to those of cortical bone. The implants were implanted bilaterally in the femoral epiphysis of 15 New Zealand White rabbits. After 3 and 8 weeks, abundant bone formation was found inside the rapid prototyped porous titanium implants. For the Ti1200 implants, bone ingrowth was (23.9 +/- 3.5)% and (10.3 +/- 2.8)%, respectively. A significant statistical difference (p < 0.05) was found for bone ingrowth in the Ti1200 between the two delays. The percentage of bone directly apposited on titanium was (35.8 +/- 5.4)% and (30.5 +/- 5.0)%. No significant difference was found for bone-implant contact between the different time periods and pore sizes. This work demonstrates that manufacturing macroporous titanium implants with controlled shape and porosity using a rapid prototyping method is possible and that this technique is a good candidate for orthopedic and maxillofacial applications.     

Design and fabrication of cast orthopedic implants with freeform surface textures from 3-D printed ceramic shell

Three-dimensional printing is a solid freeform fabrication process, which creates parts directly from a computer model. The parts are built by repetitively spreading a layer of powder and selectively joining the powder in the layer by ink-jet printing of a binder material. 3D printing was applied to the fabrication of sub-millimeter surface textures with overhang and undercut geometries for use in orthopedic prostheses as bony ingrowth structures. 3D printing is used to fabricate ceramic molds of alumina powder and silica binder, and these molds are used to cast the bony ingrowth surfaces of Co-Cr (ASTM F75) alloy. Minimum positive feature sizes of the ceramic mold and, therefore, minimum negative feature sizes of castings were determined to be approximately 200 x 200 x 175 microm and were limited by the strength of ceramic needed to withstand handling. Minimum negative feature sizes in the ceramic mold and, therefore, minimum positive features in the casting were found to be approximately 350 x 350 x 175 microm and were determined by limitations on removal of powder from the ceramic and the pressure required to fill these small features with molten metal during casting. Textures were designed with 5 layers of distinct geometric definition, allowing for the design of overhung geometry with overall porosity ranging from 30-70%. Features as small as 350 x 350 x 200 microm were included in these designs and successfully cast.     

Percutaneous implants with porous titanium dermal barriers: an in vivo evaluation of infection risk

Osseointegrated percutaneous implants are a promising prosthetic alternative for a subset of amputees. However, as with all percutaneous implants, they have an increased risk of infection since they breach the skin barrier. Theoretically, host tissues could attach to the metal implant creating a barrier to infection. When compared with smooth surfaces, it is hypothesized that porous surfaces improve the attachment of the host tissues to the implant, and decrease the infection risk. In this study, four titanium implants, manufactured with a percutaneous post and a subcutaneous disk, were placed subcutaneously on the dorsum of eight New Zealand White rabbits. Beginning at four weeks post-op, the implants were inoculated weekly with 10(8) CFU Staphylococcus aureus until signs of clinical infection presented. While we were unable to detect a difference in the incidence of infection of the porous metal implants, smooth surface (no porous coating) percutaneous and subcutaneous components had a 7-fold increased risk of infection compared to the implants with a porous coating on one or both components. The porous coated implants displayed excellent tissue ingrowth into the porous structures; whereas, the smooth implants were surrounded with a thick, organized fibrotic capsule that was separated from the implant surface. This study suggests that porous coated metal percutaneous implants are at a significantly lower risk of infection when compared to smooth metal implants. The smooth surface percutaneous implants were inadequate in allowing a long-term seal to develop with the soft tissue, thus increasing vulnerability to the migration of infecting microorganisms.     

Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes

Previous investigations have shown that both the early biological response and the mechanical properties of a porous hydroxyapatite bone graft substitute are highly sensitive to its pore structure. The objective of this study was to evaluate whether the pore structure continued to influence bone integration in the medium to long term. Two screened batches of porous hydroxyapatite (PHA) designated as batch A and batch B, with porosities of approximately 60 and 80%, respectively, were selected for this study and implanted for periods of 5, 13, and 26 weeks into the lower femur of New Zealand White rabbits. Histomorphometric analysis of the absolute volume of bone ingrowth within batch A and B implants from 5 to 26 weeks showed that the absolute volume of bone ingrowth was consistently lower in batch A (10-21%), compared to batch B implants (24-31%). However, when the volume of bone ingrowth was normalised for the available pore space, this difference was reduced (23-47% and 32-42% for batches A and B, respectively). These observations suggest that differences in the volume of bone ingrowth initially depended on pore interconnectivity rather than pore size, whereas the volume or morphology of the PHA influenced the volume and morphology of bone ingrowth at later time points. Compression testing showed that bone ingrowth had a strong reinforcing effect on PHA bone graft substitutes, and a strong correlation was identified between mechanical properties and the absolute volume of ingrowth for both batches A and B. Furthermore, at 13 and 26 weeks, there was no significant variation in the ultimate compressive strength of integrated batch A and B implants. This similarity in ultimate mechanical properties indicated that the absolute volume of ingrowth may be mediated by the PHA structure through its impact on the dynamics of the local biomechanical environment. The results of push-out testing showed that fixation of PHA bone graft substitutes was independent of density within the range studied, with no significant difference in the interfacial shear stress between batches A and B at each time point throughout the study.     

Interfacial shear strength of titanium implants in bone is significantly improved by surface topographies with high pit density and microroughness

Surface structure of implants influences bone response and interfacial shear strength between implants and bone. The aim of this study was to find topographical parameters that correlate with the interfacial shear strength. Two groups of sand-blasted titanium screws were implanted in 17 sheep tibia, each for 2-52 weeks: (A) acid pickled with HF/HNO(3); (B) acid etched with HCl/H(2)SO(4). Screw removal torque was measured and surface topography of both implant groups was studied by scanning electron microscopy, optical profilometry, and scanning probe microscopy. The roughness as well as the surface area of type A surface was higher in the scan region of 100 microm, but the microroughness and surface area of type B surface was higher in the scan region of 10 microm. A significantly higher removal torque (interfacial shear strength) of the surface treatment type B (412 +/- 60 Ncm) compared to surface treatment type A (157 +/- 33 Ncm) was found after 52 weeks of implantation in sheep due to differences in microroughness of both types of screws. It was also shown that the specification of the parameters Delta(a), R(a) and R(q) was not sufficient to characterize the properties of the implant surfaces. The analysis of R(q) parameter over wavelengths was required to characterize the size, shape and distribution of the implant surface structures.     

Integrity of the stem-cement interface in THA: effects of stem surface finish and cement porosity

No consensus exists for the optimal surface finish on cemented total hip prosthesis stems. The purpose of this study was to determine the effects of stem finish and interfacial cement porosity on the integrity of the stem-cement interface. Simulated stems made of Co-Cr, having polished or matte surfaces, at room temperature or heated to 37 degrees C, were cemented into Sawbones simulated femurs. Push out testing of the stem-cement interface was performed immediately after cement polymerization and after two aging periods in 37 degrees C saline or 37 degrees C air, and the extent of interfacial porosity at the stem-cement interface was determined. Polished stems exhibited an average 60% greater interfacial strength than that of matte stems initially and up to 240% after aging treatments. Cement porosity at the stem-cement interface and incomplete cement interdigitation into surface asperities on matte stems likely allowed saline penetration into the stem-cement interface during wet aging, resulting in a rapid decrease of shear strength. Stem preheating to 37 degrees C virtually eliminated interfacial pores and resulted in greater shear strengths regardless of surface finish. Polished stem surfaces with stem preheating provided the best interfacial shear strength and sealing ability against saline penetration into the stem-cement interface and could result in increased longevity of stem fixation.     

In vivo evaluation of plasma-sprayed titanium coating after alkali modification

In this paper, plasma-sprayed titanium coatings were modified by alkali treatment. The changes in chemical composition and structure of coatings were examined by SEM and AES. The results obtained indicated that a net-like microscopic texture feature, which was full of the interconnected fine porosity, appeared on the surface of alkali-modified titanium coatings. The surface chemical composition was also altered by alkali modification. A sodium titanate compound was formed on the surface of the titanium coating and replaced the native passivating oxide layer. Its thickness was measured as about 150 nm which was about 10 times of that of the as-sprayed coating. The bone bonding ability of titanium coatings were investigated using a canine model. The histological examination and SEM observation demonstrated that more new bone was formed on the surface of alkali-modified implants and grew more rapidly into the porosity. The alkali-modified implants were found to appose directly to the surrounding bone. In contrast, a gap was observed at the interface between the as-sprayed implants and bone. The push-out test showed that alkali-modified implants had a higher shear strength than as-sprayed implants after 1 month of implantation. An interfacial layer, containing Ti, Ca and P, was found to form at the interface between bone and the alkali-modified implant by EDS analysis.     

Influence of porosity on mechanical properties and in vivo response of Ti6Al4V implants

Metallic biomaterials are widely used to restore the lost structure and functions of human bone. Due to the large number of joint replacements, there is a growing demand for new and improved orthopedic implants. More specifically, there is a need for novel load-bearing metallic implants with low effective modulus matching that of bone in order to reduce stress shielding and consequently increase the in vivo lifespan of the implant. In this study, we have fabricated porous Ti6Al4V alloy structures, using laser engineered net shaping (LENS?), to demonstrate that advanced manufacturing techniques such as LENS? can be used to fabricate low-modulus, tailored porosity implants with a wide variety of metals/alloys, where the porosity can be designed in areas based on the patient’s need to enhance biological fixation and achieve long-term in vivo stability. The effective modulus of Ti6Al4V alloy structures has been tailored between 7 and 60 GPa and porous Ti alloy structures containing 23–32 vol.% porosity showed modulus equivalent to human cortical bone. In vivo behavior of porous Ti6Al4V alloy samples in male Sprague–Dawley rats for 16 weeks demonstrated a significant increase in calcium within the implants, indicating excellent biological tissue ingrowth through interconnected porosity. In vivo results also showed that total amount of porosity plays an important role in tissue ingrowth.     

Pore distribution and material properties of bone cement cured at different temperatures

Implant heating has been advocated as a means to alter the porosity of the bone cement/implant interface; however, little is known about the influence on cement properties. This study investigates the mechanical properties and pore distribution of 10 commercially available cements cured in molds at 20, 37, 40 and 50 °C. Although each cement reacted differently to the curing environments, the most prevalent trend was increased mechanical properties when cured at 50 °C vs. room temperature. Pores were shown to gather near the surface of cooler molds and near the center in warmer molds for all cement brands. Pore size was also influenced. Small pores were more often present in cements cured at cooler temperatures, with higher-temperature molds producing more large pores. The mechanical properties of all cements were above the minimum regulatory standards. This work shows the influence of curing temperature on cement properties and porosity characteristics, and supports the practice of heating cemented implants to influence interfacial porosity.     

Porous poly(DL-lactic-co-glycolic acid)/calcium phosphate cement composite for reconstruction of bone defects

Calcium phosphate (Ca-P) cements are injectable, self-setting ceramic pastes generally known for their favorable bone response. Ingrowth of bone and subsequent degradation rates can be enhanced by the inclusion of macropores. Initial porosity can be induced by CO(2) foaming during setting of the cement, whereas secondary porosity can develop after hydrolysis of incorporated poly(DL-lactic- co-glycolic acid) (PLGA) microparticles. In this study, we focused on the biological response to porous PLGA/Ca-P cement composites. Pre-set composite discs of four formulations (4 wt% or 15 wt% PLGA microparticles and low or high CO(2) induced porosity) were implanted subcutaneously and in cranial defects in rats for 12 weeks. Histological analysis of the explanted composites revealed that bone and fibrous tissue ingrowth was facilitated by addition of PLGA microparticles (number average diameter of 66 +/- 25 microm). No adverse tissue reaction was observed in any of the composites. Significant increases in composite density due to bone ingrowth in cranial implants were found in all formulations. The results suggest that the PLGA pores are suitable for bone ingrowth and may be sufficient to enable complete tissue ingrowth without initial CO(2) induced porosity. Finally, bone-like mineralization in subcutaneous implants suggests that, under appropriate conditions and architecture, porous PLGA/Ca-P cement composites can exhibit osteoinductive properties. These PLGA/Ca-P composites are a promising scaffolding material for bone regeneration and bone tissue engineering.