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Effect of gamma-radiation on a polyanhydride implant containing gentamicin sulfate.

Septacin, a polyanhydride implant containing gentamicin sulfate, was sterilized by gamma-radiation. Its copolymer molecular weight (M(w) by GPC) was increased after this radiation. No cross-linking was shown in the radiated samples as no gel content was found by the filtration method. The chemical structure as detected by 1H NMR for non-radiated and radiated samples was comparable. For samples radiated at higher dose levels (70-100 kGy), the IR spectra showed that the intensity of absorbance attributable to the C-H stretching vibration (at 2852 and 2927 cm(-1)) was attenuated, indicating free-radical formation or loss of hydrogen atoms from C-H bonds. However, the mass spectra for the gamma-radiated and the non-radiated controls after they were completely depolymerized in methylene chloride were virtually identical. Therefore, it could be concluded that the increase in copolymer molecular weight for radiated Septacin was a result of chain extension in the copolymer backbone during radiation. In addition, wide-angle X-ray diffraction and polarizing light microscopy (PLM) revealed a change in the physical structure of the radiated copolymer. There was an increase in crystallinity of the copolymer with increasing radiation doses; the greatest increase in crystallinity occurred at the dose range of 70-80 kGy, which was also shown to result in the greatest molecular-weight increase. The crystalline morphology of the samples as detected by PLM was not altered by gamma-radiation, regardless of the dose levels.

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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.

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Preparation of and tissue response to DNA-lipid films.

DNA-containing films have the potential to form complexes with antibiotics or cytokines by intercalation or groove-binding. This principle can be highly relevant for regenerative wound-healing around oral implants and in periodontology. In this study, we prepared DNA-lipid films and examined tissue responses to them as an indicator of their biological properties. The lipids were synthesized from the reaction of L-alanine, n-alkyl alcohol, and p-toluenesulfonic acid. We prepared the self-standing, water-insoluble DNA-lipid films by casting the DNA-lipid complex from chloroform/ethanol solution. The DNA-lipid complexes, which had 1:1 ratios of phosphate anions to cationic lipid, were found to have a double-helical B-form structure. The DNA-lipid films were almost dissolved 3 days after subcutaneous implantation in the backs of rats. There were no inflammatory reactions or inhibition of new tissue formation. We concluded that DNA-lipid films can be prepared by simple methods, and that they do not cause an unfavorable tissue response.

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Bone-like polyethelyne burr-hole cover.

OBJECTIVE: Several materials are available for covering burr holes but none of them are ideal with respect to biocompatibility, strength and morbidity. With these properties in mind, our objective was to design a porous polyethylene device, which looked like bone and provides protection and cosmesis while being quick and easy to apply. METHODS AND MATERIALS/RESULTS: A burr-hole cover was created to cover small cranial defects and craniostomies. Using high-density polyethylene, this cover was designed to resemble the bony structure of the skull. Its porous architecture allows for tissue ingrowth and bony integration. It consists of a cylinder which fits into the burr hole and a cap which can be sutured or anchored with titanium screws. CONCLUSIONS: The "bone-like" burr-hole cover provides adequate protection, biocompatibility and cosmesis and is simple to use. Alternative implants can be toxic to surrounding tissues, costly and time consuming to apply. This high-density polyethylene cover is compatible with surrounding tissue as well as being of a porous nature and the material it is made from offers high tensile strength for adequate protection.

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Treatment of syndesmotic disruptions of the ankle with bioabsorbable screw fixation.

BACKGROUND: Bioabsorbable implants have restricted indications because of their unique biochemical properties and their inferior biomechanical properties compared with those of conventional metallic implants. The purpose of this prospective study was to assess the efficacy of screws made of polylevolactic acid (PLLA) in the treatment of syndesmotic disruptions associated with ankle fractures and fracture-dislocations. METHODS: Thirty-three consecutive patients with a syndesmotic disruption were managed with standard metallic plate-and-screw fixation of the malleolar fracture and with 4.5-mm polylevolactic acid screws, with purchase in four cortices, for fixation of the syndesmosis. Intraoperative radiographs confirmed reduction of the syndesmosis, and all of the patients were managed with a non-weight-bearing plaster splint or brace for six weeks. Clinical and radiographic assessment and functional evaluation with use of the Olerud-Molander scoring system were performed at the time of follow-up. RESULTS: Ten patients were lost to follow-up prior to the twenty-four-month evaluation, leaving twenty-three patients with an average duration of follow-up of thirty-four months (range, twenty-four to forty-three months). All of the malleolar fractures healed in an anatomical position at an average of three months, and no postoperative displacement of the syndesmosis or widening of the medial clear space was detectable on radiographs. No episodes of osteolysis or late inflammation secondary to the hydrolyzed polylactide occurred. Nineteen patients (83%) had an excellent result, and four patients (17%) had a good result. All twenty-three patients returned to their preinjury level of work and activities of daily living. No patient had malunion, nonunion, loss of reduction, or complications attributable to the biomechanical or biochemical properties of the implants. CONCLUSIONS: Polylevolactic acid screws are effective in stabilizing disruption of the syndesmosis during healing of unstable ankle fractures. In this small series, the bioabsorbable screw was well tolerated, and there was no need for a second operation to remove it.

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A new bone-inducing biodegradable porous beta-tricalcium phosphate.

A new type of degradable biomaterial with bone-inducing capacity was made by combining porous beta-tricalcium phosphate (beta-TCP) with a delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2). The BMP delivery system consisted of a block copolymer composed of poly-D,L-lactic acid with random insertion of p-dioxanone and polyethylene glycol (PLA-DX-PEG), a known biocompatible and biodegradable material. The efficacy of this biomaterial in terms of its bone-inducing capacity was examined by ectopic bone formation in the dorsal muscles of the mouse. In the beta-TCP implants coated with the PLA-DX-PEG polymer containing more than 0.0025% (w/w) of rhBMP-2, new ectopic bone tissues with marrow were consistently found on the surface of implants. The radiographic density of beta-TCP was diminished in a time-dependent manner. On histological examination, numerous multinucleated osteoclasts with positive tartrate-resistant acid-phosphatase (TRAP) staining were noted on the surface of the beta-TCP. These experimental results indicate that beta-TCP implants coated with synthetic rhBMP-2 delivery system might provide effective artificial bone-graft substitutes with osteoinductive capacity and biodegradable properties. In addition, this type of biomaterial may require less rhBMP-2 to induce significant new bone mass.

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Cementoblast delivery for periodontal tissue engineering.

BACKGROUND: Predictable periodontal regeneration following periodontal disease is a major goal of therapy. The objective of this proof of concept investigation was to evaluate the ability of cementoblasts and dental follicle cells to promote periodontal regeneration in a rodent periodontal fenestration model. METHODS: The buccal aspect of the distal root of the first mandibular molar was denuded of its periodontal ligament (PDL), cementum, and superficial dentin through a bony window created bilaterally in 12 athymic rats. Treated defects were divided into three groups: 1) carrier alone (PLGA polymer sponges), 2) carrier + follicle cells, and 3) carrier + cementoblasts. Cultured murine primary follicle cells and immortalized cementoblasts were delivered to the defects via biodegradable PLGA polymer sponges, and mandibulae were retrieved 3 weeks and 6 weeks post-surgery for histological evaluation. In situ hybridization, for gene expression of bone sialoprotein (BSP) and osteocalcin (OCN), and histomorphometric analysis were further done on 3-week specimens. RESULTS: Three weeks after surgery, histology of defects treated with carrier alone indicated PLGA particles, fibrous tissue, and newly formed bone scattered within the defect area. Defects treated with carrier + follicle cells had a similar appearance, but with less formation of bone. In contrast, in defects treated with carrier + cementoblasts, mineralized tissues were noted at the healing site with extension toward the root surface, PDL region, and laterally beyond the buccal plate envelope of bone. No PDL-bone fibrous attachment was observed in any of the groups at this point. In situ hybridization showed that the mineralized tissue formed by cementoblasts gave strong signals for both BSP and OCN genes, confirming its nature as cementum or bone. The changes noted at 3 weeks were also observed at 6 weeks. Cementoblast-treated and carrier alone-treated defects exhibited complete bone bridging and PDL formation, whereas follicle cell-treated defects showed minimal evidence of osteogenesis. No new cementum was formed along the root surface in the above two groups. Cementoblast-treated defects were filled with trabeculated mineralized tissue similar to, but more mature, than that seen at 3 weeks. Furthermore, the PDL region was maintained with well-organized collagen fibers connecting the adjacent bone to a thin layer of cementum-like tissue observed on the root surface. Neoplastic changes were observed at the superficial portions of the implants in two of the 6-week cementoblast-treated specimens, possibly due in part to the SV40-transformed nature of the implanted cell line. CONCLUSIONS: This pilot study demonstrates that cementoblasts have a marked ability to induce mineralization in periodontal wounds when delivered via polymer sponges, while implanted dental follicle cells seem to inhibit periodontal healing. These results confirm the selective behaviors of different cell types in vivo and support the role of cementoblasts as a tool to better understand periodontal regeneration and cementogen-

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Optimal biomaterial for creation of autologous cardiac grafts.

BACKGROUND: The optimal cardiac graft for the repair of congenital heart defects will be composed of autologous cells and will grow with the child. The biodegradable material should permit rapid cellular growth and delayed degradation with minimal inflammation. We compared a new material, epsilon-caprolactone-co-L-lactide sponge reinforced with knitted poly-L-lactide fabric (PCLA), to gelatin (GEL) and polyglycolic acid (PGA), which are previously evaluated materials. METHODS: Syngenic rat aortic smooth muscle cells (SMCs, 2x10(6)) were seeded onto GEL, PGA, and PCLA patches and cultured (n=11 per group). The DNA content in each patch was measured at 1, 2, and 3 weeks after seeding. Histological examination was performed 2 weeks after seeding. Cell-seeded patches were employed to replace a surgically created defect in the right ventricular outflow tract (RVOT) of rats (n=5 per group). Histology was studied at 8 weeks following implantation. RESULTS: In vitro studies showed that the DNA content increased significantly (P<0.05) in all patches between 1 and 3 weeks after seeding. Histology and staining SMCs for anti-alpha-smooth muscle actin (alphaSMA) revealed better growth of cells in the interstices of the grafts with GEL and PCLA than the PGA graft. In vivo studies demonstrated that seeded SMCs survived at least 8 weeks after the patch implantation in all groups. PCLA scaffolds were replaced by more cells with larger alphaSMA-positive areas and by more extracellular matrix with larger elastin-positive areas than with GEL and PGA. The patch did not thin and expanded significantly. The GEL and PGA patches thinned and expanded. All grafts had complete endothelialization on the endocardial surface. CONCLUSIONS: SMC-seeded biodegradable materials can be employed to repair the RVOT. The novel PCLA patches permitted better cellular penetration in vitro and did not thin or dilate in vivo and did not produce an inflammatory response. The cell-seeded PCLA patch may permit the construction of an autologous patch to repair congenital heart defects.

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Cyclic joint loading can affect the initial stability of meniscal fixation implants.

OBJECTIVE: To identify the effect of cyclic joint loads on the initial fixation strength of different meniscal repair techniques. DESIGN: Three different meniscal refixation implants and one suturing technique were tested for initial stability in porcine knee joints after cyclic joint loading. BACKGROUND: Existing studies tested the initial pull out strength of meniscal fixation implants. It remains unknown how such implants perform under cyclic joint loading. METHODS: The Meniscal Fastener, the Meniscal Arrow, the ClearFix Screw, and a horizontal suture (PDS 1) were implanted in 64 porcine knee joints after setting a tear in the posterior horn of the medial meniscus. In one group of each device the menisci were excised directly after implantation and subsequently subjected to a pull out test. The knee joints of the other groups were exposed to 5000 axial load cycles between 10 and 200 N prior to the pull out test. RESULTS: The horizontal suture showed the highest pull out force (103 N, SD 19 N). Arrow (52 N, SD 18 N), Meniscal Fastener (29 N, SD 3 N), and Meniscal Screw (22 N, SD 8 N) failed at significantly lower loads. Cyclic loading led to a decreased initial pull out force only for the horizontal suture (82 N, SD 26 N) and the Meniscal Fastener (23 N, SD 5N). CONCLUSIONS: Cyclic joint loading can lead to reduced fixation strength especially of meniscal refixation implants and sutures with relatively low stiffness. However, it remains unclear which fixation strength is necessary to provide conditions for meniscal healing. RELEVANCE: The current study adds information to the understanding of how meniscal fixation systems perform mechanically especially after cyclic joint loads.

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Poly lactic acid--caprolactone copolymer tube with a denatured skeletal muscle segment inside as a guide for peripheral nerve regeneration: a morphological and electrophysiological evaluation of the regenerated nerves.

A biodegradable copolymer of poly L-lactic acid and epsilon-caprolactone (PLAC) was manufactured into a tube, in which a denatured skeletal muscle segment was placed longitudinally. This model tube was implanted as a guide to promote nerve regeneration across a 5 cm gap in the rabbit sciatic nerve. Five months after implantation, good nerve regeneration was found throughout the graft and in the distal host nerve. The population (29.6/16 x 10(2) microm(2)) of regenerated nerves in the graft was higher than that of the contralateral normal sciatic nerve (18.0/16 x 10(2) microm(2)). Regenerated nerve fibers extended to the distal host nerve. The number of myelinated fibers was 13.7/16 x 10(2) microm(2) at a level 1.5 cm from the distal suture. The diameters (below 2 microm) of most regenerated myelinated (nerves in the graft and in the distal host nerve were much smaller than those (6-8 microm) of normal nerves. Electrophysiological evaluation showed that the hindlimb muscle (gastrocnemius) was innervated by motor nerves in all animals 5 months after implantation. These results indicate that the PLAC tube with a denatured muscle segment inside provided good conditions for nerve fiber regrowth. The PLAC tube is thought to protect the denatured muscle segment from rapid dissociation in the host tissue.

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Mechanical testing of bioresorbable implants for use in metacarpal fracture fixation.

The purpose of this study was to evaluate the mechanical properties of a bioresorbable plate and screw system that was developed for the treatment of unstable metacarpal fractures and to compare the strength and stiffness of this system with those of conventional titanium plates and screws. Using a 4-point bending test, we measured the strength and stiffness of these implants over a 12-week period of in vitro degradation. Our data suggest that these implants provide stable bending strength and stiffness for 8 weeks and gradually lose their strength over a period of 12 weeks. Further research is necessary to determine whether this level of fixation is adequate to stabilize unstable metacarpal fractures.

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Experience with freeze-dried PGLA/HA/rhBMP-2 as a bone graft substitute.

We investigated bone induction by recombinant human bone morphogenetic protein-2 in rodents. The purpose of this study was to evaluate the osteoinductive potential of a resorbable bone substitute fabricated from freeze-dried poly(glycolic acid-co-lactic acid) (PGLA) mixed with hydroxyapatite particles incorporated with bone morphogenetic protein-2 in skull defects of rats (FD-PGLA/HA/rhBMP-2). The FD-PGLA/HA/rhBMP-2 composite or as a control, the FD-PGLA/HA by itself were implanted in skull defects (psi 8 mm) of rats. The samples were harvested at 2 or 4 weeks postoperatively and were studied radiographically and histologically. Four weeks after implantation, the FD-PGLA/HA/rhBMP-2 discs were completely replaced by newly-formed bone possessing bone marrow. In contrast, the defects implanted with FD-PGLA/HA were filled only with fibrous connective tissue. The results suggest that the FD-PGLA/HA/rhBMP-2 composite could be an optimum bone substitute with osteoinductive potential and could function as an alternative bone graft material for autogenous bone in humans.

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Biocompatibility of composite membrane consisting of oriented needle-like apatite and biodegradable copolymer with soft and hard tissues in rats.

The purpose of this study was to evaluate histologically the reaction of soft and hard tissues in rats toward a composite membrane consisting of oriented needle-like apatite crystals and biodegradable copolymer. Histological findings regarding the soft tissue reaction showed that the membrane with or without apatite was covered by fibrous connective tissue at four weeks after implantation. In the case of hard tissue, the defect in dura mater--which was covered with an apatite-containing membrane--was fully filled with new bone at four weeks after implantation. As for the membrane without apatite, there was some indication of a granulation tissue reaction around the membrane. These results suggested that the biodegradable composite membrane containing oriented needle-like apatite had excellent biocompatibility with both soft and hard tissues.

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Bioresorbable poly-L/DL-lactide (P[L/DL]LA 70/30) plates are reliable for repairing large inferior orbital wall bony defects: a pilot study.

PURPOSE: The purpose of this study was to share our clinical experience on the use of bioresorbable poly-L/DL-lactide implants (P[L/DL]LA) 70/30 (PolyMax; Synthes, Oberdorf, Switzerland) to repair, large (> or =2 cm2), inferior orbital wall defects and to evaluate whether P(L/DL)LA 70/30 implants adequately support the orbital soft tissue contents. PATIENTS AND METHODS: Thirteen patients who suffered orbital blowout fractures, with > or =2 cm2 bony defects in the inferior orbital wall, took part in the study. The inferior orbital wall was explored via subconjunctival approach. After repositioning of orbital content, each inferior orbital wall was reconstructed using a round plate of P(L/DL)LA 70/30. Computed tomography and magnetic resonance imaging coronal sections were undertaken before the operation and 2 and 36 weeks postoperatively. RESULTS: The magnetic resonance imaging studies showed no abnormal tissue foreign body reactions in the orbital region. The material showed adequate strength to stabilize bone segments during the critical period of bone healing. The bone healing seems to take place along the bone fragments. The clinical outcome was excellent in 11 of the 13 cases (85%). At the end of the study, only one patient had mild enophthalmos. CONCLUSIONS: Bioresorbable P(L/DL)LA 70/30 implants are safe and reliable for the repair of large defects (> or =2 cm2) in the inferior orbital wall. It seems that this is the first reported biodegradable material, in the literature, to promote bone healing along the bone fragments of the inferior orbital wall.

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In vivo characterisation of a novel bioresorbable poly(lactide-co-glycolide) tubular foam scaffold for tissue engineering applications.

Polylactide-co-glycolide (PLGA) foams of tubular shape were assessed for their use as soft-tissue engineering scaffolds in vitro and in vivo. Porous membranes were fabricated by a thermally induced phase separation process of PLGA solutions in dimethylcarbonate. The parameters investigated were the PLGA concentration and the casting volume of solution. Membranes produced from 5 wt/v % polymer solutions and a 6 ml casting volume of polymer solution were selected for fabricating tubes of 3 mm diameter, 20 mm length and a nominal wall thickness of 1.5 mm. Scanning electron microscopy revealed that the structure of the tubular foams consisted of radially oriented and highly interconnected pores with a large size distribution (50-300 microm). Selected tubes were implanted subcutaneously into adult male Lewis rats. Although the lumen of the tubes collapsed within one week of implantation, histological examination of the implanted scaffolds revealed that the foam tubes were well tolerated. Cellular infiltration into the foams, consisting mainly of fibrovascular tissue, was evident after two weeks and complete within eight weeks of implantation. The polymer was still evident in the scaffolds after eight weeks of implantation. The results from this study demonstrate that the PLGA tubular foams may be useful as soft-tissue engineering scaffolds with modification holding promise for the regeneration of tissues requiring a tubular shape scaffold such as intestine.

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Biomechanical analysis of biodegradable interbody fusion cages augmented With poly(propylene glycol-co-fumaric acid).

STUDY DESIGN: Three different types of biodegradable poly(L-lactide-co-D,L-lactide) cages with and without augmentation of a biodegradable poly(propylene glycol-cofumaric acid) scaffold were compared with autograft and metallic cages of the same design and size by determining the stiffness and failure load of the L4-L5 motion segment of cadaveric human spines. OBJECTIVES: To determine how these devices limit the range of motion in the lumbar spine compared with a metallic cage. If biomechanically equivalent, biodegradable spinal fusion systems ultimately could reduce local stress shielding and diminish the incidence of clinical complications, including device-related osteopenia, implant loosening, and breakage. SUMMARY OF BACKGROUND DATA: Previous studies in dogs and humans have demonstrated vertebral body osteopenia as a result of instrumented spine fusions. To the authors' knowledge, neither an in vitro nor an in vivo biomechanical analysis of a biodegradable interbody fusion system has been performed. METHODS: Forty-eight L4-L5 motion segments were isolated from 22 male and 26 female human donors with an average age of 49.6 +/- 2.7 years (range 36-55 years). Cages of similar dimensions and design, including a threaded, hollow, porous titanium BAK cage and three different BIO cages (BIO cage 1, pure polymer; BIO cage 2, polymer plus hydroxyapatite buffer; BIO cage 3, polymer plus nano-sized hydroxyapatite), produced from the same poly(L-lactide-co-D,L-lactide) polymer were tested in a comparative analysis to intact motion segment, interbody implantation of autograft, and a BIO cage augmented with an expandable biodegradable foam-scaffold fashioned from poly(propylene glycol-cofumaric acid). RESULTS: All cages were able to increase stiffness and failure load of the unstable motion segment significantly (P < 0.01). In comparison with the bone graft, the BAK cage (P < 0.01) and BIO cages 1 and 3 (P < 0.05) were able to increase stiffness and failure load. There was no significant difference between BIO cage 2 and the bone graft. Augmentation of BIO cage 1 with the foaming PPF scaffold resulted in higher stiffness and similar failure load as seen with the BAK cage. CONCLUSION: By comparison, the in vitro lumbar spinal motion segment stiffness and failure load produced by implantation of a biodegradable interbody fusion cage augmented with an expandable PPF scaffold is similar to that of the titanium BAK cage. This suggests that biodegradable anterior interbody fusion systems could be further developed for clinical applications.

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Experimental corneal neovascularization by basic fibroblast growth factor incorporated into gelatin hydrogel.

The study was designed to investigate the feasibility of using an acidic gelatin hydrogel as a biodegradable vehicle for basic fibroblast growth factor (bFGF). bFGF was incorporated by polyion complexation into a biodegradable hydrogel prepared by cross-linking acidic gelatin with the isoelectric point of 4.9. The dried hydrogel (sized to 2x1 mm) was hydrated with bFGF aqueous solution including different doses of bFGF (20, 50, 125, 250 and 500 ng) and implanted into a rabbit corneal pocket (2.5x2 mm). As a control group, the gelatin hydrogel without bFGF or bFGF alone (500 ng) was used. Corneal angiogenesis was evaluated by biomicroscopy, corneal fluorescein angiography and histology for 21 days. Photographs were taken and corneal angiogenesis was evaluated by image analysis. The hydrogel degraded with time after its implantation into the corneal pocket. Experimental eyes receiving the hydrogel containing more than 50 ng of bFGF demonstrated significant corneal angiogenesis. Control eyes and eyes receiving the hydrogel containing 20 ng of bFGF showed no corneal angiogenesis. Corneal angiogenesis, which occurred on the 3rd or 4th day after implantation, reached maximal growth on about day 7 and regressed from day 10 after implantation. The area of angiogenesis showed a dose-dependency on bFGF. The gelatin hydrogel itself induced neither angiogenesis nor inflammation. These results suggested that acidic gelatin hydrogel releases bioactive bFGF with its biodegradation, resulting in corneal neovascularization.

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In vivo investigations on composites made of resorbable ceramics and poly(lactide) used as bone graft substitutes.

Porous composites made of poly(L, DL-lactide) (PLA) and alpha-tricalcium phosphate (alpha-TCP) or the glass ceramic, GB14N, respectively, were investigated in a loaded implant model in sheep. Six, 12 and 24 months after implantation histological and biomechanical evaluation were performed and compared to autogenous bone transplants. No significant differences were observed between the composites. After 6 months, the interconnecting pores of the alpha-TCP-composite and the GB14N-composite were filled with newly formed bone (14 +/- 5% or 29 +/-15% of the implant, respectively) and soft tissue (30 +/-9% or 21 +/-12% of the implant, respectively). Only a mild inflammatory response was observed. The reaction was similar after 12 months. However, after 24 months a strong inflammatory reaction was seen. The newly formed bone was partly osteolytic. The adverse reaction occurred simultaneously to a significant reduction of the PLA component. The histological results were reflected by the biomechanical outcomes. Both composites showed compression strengths in the range of the autologous bone graft until 12 months of implantation. After 2 years, however, the strengths were significantly decreased. It is concluded that the new composites cannot yet be used for clinical application. An improvement in biocompatibility might be reached by a better coordination of the degradation times of the polymer and the ceramic component.

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