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Most synthetic bone grafts are either hard and brittle ceramics or paste-like materials that differ in applicability from the gold standard autologous bone graft, which restricts their widespread use. Therefore, the aim of the study was to develop an elastic, highly porous and biodegradable β-tricalciumphosphate/poly(L-lactide-co-ε-caprolactone) (β-TCP/PLCL) composite for bone applications using supercritical CO2 foaming. Ability to support osteogenic differentiation was tested in human adipose stem cell (hASC) culture for 21 d. Biocompatibility was evaluated for 24 weeks in a rabbit femur-defect model. Foamed composites had a high ceramic content (50 wt%) and porosity (65-67 %). After 50 % compression, in an aqueous environment at 37 °C, tested samples returned to 95 % of their original height. Hydrolytic degradation of β-TCP/PLCL composite, during the 24-week follow-up, was very similar to that of porous PLCL scaffold both in vitro and in vivo. Osteogenic differentiation of hASCs was demonstrated by alkaline phosphatase activity analysis, alizarin red staining, soluble collagen analysis, immunocytochemical staining and qRT-PCR. In vitro, hASCs formed a pronounced mineralised collagen matrix. A rabbit femur defect model confirmed biocompatibility of the composite. According to histological Masson-Goldner's trichrome staining and micro-computed tomography, β-TCP/PLCL composite did not elicit infection, formation of fibrous capsule or cysts. Finally, native bone tissue at 4 weeks was already able to grow on and in the β-TCP/PLCL composite. The elastic and highly porous β-TCP/PLCL composite is a promising bone substitute because it is osteoconductive and easy-to-use and mould intraoperatively.

The advantages of synthetic bone graft substitutes over autogenous bone grafts include abundant graft volume, lack of complications related to the graft harvesting, and shorter operation and recovery times for the patient. We studied a new synthetic supercritical CO 2 -processed porous composite scaffold of β-tricalcium phosphate and poly(L-lactide-co-caprolactone) copolymer as a bone graft substitute in a rabbit calvarial defect. Bilateral 12 mm diameter critical size calvarial defects were successfully created in 18 rabbits. The right defect was filled with a scaffold moistened with bone marrow aspirate, and the other was an empty control. The material was assessed for applicability during surgery. The follow-up times were 4, 12, and 24 weeks. Radiographic and micro-CT studies and histopathological analysis were used to evaluate new bone formation, tissue ingrowth, and biocompatibility. The scaffold was easy to shape and handle during the surgery, and the bone-scaffold contact was tight when visually evaluated after the implantation. The material showed good biocompatibility and its porosity enabled rapid invasion of vasculature and full thickness mesenchymal tissue ingrowth already at four weeks. By 24 weeks, full thickness bone ingrowth within the scaffold and along the dura was generally seen. In contrast, the empty defect had only a thin layer of new bone at 24 weeks. The radiodensity of the material was similar to the density of the intact bone. In conclusion, the new porous scaffold material, composed of microgranular β-TCP bound into the polymer matrix, proved to be a promising osteoconductive bone graft substitute with excellent handling properties.

The ability of transforming growth factor-beta 1 (TGF-beta 1) to promote bone formation suggests that it may have potential as a therapeutic agent in bone defects. However, there still exists a need for an effective method of delivering TGF-beta 1 to the site of an osseous defect. In the present study, TGF-beta 1 was embedded in a bioabsorbable polymer paste (a blend of an L-lactide oligomer and a copolymer of epsilon-caprolactone and DL-lactide). The release of TGF-beta 1 from the polymer paste was examined in vitro with an enzyme-linked immunosorbent assay, which showed sustained release of active TGF-beta 1 over a 7-day period. Further, the polymer paste was used to fill a bone defect in the rat distal femur. The amount of TGF-beta 1 per rat was 50 micrograms, while in a control group we used an identical polymer paste without the growth factor. After a follow-up of 1 week and 3 weeks, the femurs were examined radiographically, histologically, histomorphometrically, microradiographically, and were also used for tetracycline-labeling studies. TGF-beta 1 did not enhance healing of the bone defect. A combination of growth factors would probably be a more potent osteoinductor than TGF-beta 1 alone.

The effect of a bioabsorbable pin containing transforming growth factor-beta(1) on fracture healing was studied in a rat model. The growth factor was mixed into a bioabsorbable polymer paste (a blend of an l-lactic acid oligomer and a copolymer of epsilon-caprolactone and dl-lactide) that was used to fill the grooves of a self-reinforced fracture fixation pin made of a poly-ld-lactic acid copolymer. In an in vitro assay, sustained release of the growth factor from the pins over a 7-day period was demonstrated. A distal femoral osteotomy was made in 60 rats and stabilized with the fracture fixation pin in 48 of them; In the remaining 12 rats, no fixation was performed. The pin used in the study group contained either 5 microg (15 rats) or 50 microg (15 rats) of the growth factor, while in a control group of 18 rats an identical pin without the growth factor was used. After a follow-up of 1, 3, or 6 weeks, the femurs were examined radiographically, histologically, histomorphometrically, and microradiographically, and also used in tetracycline labeling studies. Faster callus formation was evident in the growth factor-treated rats but no acceleration in the healing of the osteotomy was detected.

The effect of an absorbable pin containing transforming growth factor beta 1 on fracture healing was studied in a rat model of delayed osteotomy fixation. Transforming growth factor beta 1 was mixed into a blend of L-lactide oligomer and a copolymer of epsilon-caprolactone and DL-lactide that was placed in the grooves of a self reinforced fracture fixation pin made of poly-LD-lactic acid copolymer. A distal femoral osteotomy was made in 54 rats and left untreated. A week later surgery was performed to fix the osteotomy with a fracture fixation pin in 48 rats. In the remaining six rats no fixation was performed. The pin that was used in the study group contained either 5 micrograms (15 rats) or 50 micrograms (15 rats) of the growth factor, while in the control group of 18 rats, an identical pin without growth factor was used. The femurs were examined radiographically, histologically, histomorphometrically, and microradiographically. Tetracycline labeling studies were used after a followup of 1, 3, and 6 weeks. Faster callus formation in the transforming growth factor beta 1 treated animals but no acceleration in the healing of the osteotomy is reported. The addition of bone growth factors to bioabsorbable fracture fixation materials may enhance bone healing.

The objective of the study was to evaluate the use of a totally biodegradable fixation device in the fixation of mandibular osteotomy in sheep. Mandibular unilateral body osteotomies were fixed with biodegradable self-reinforced poly-L-lactide (SR-PLLA) multi-layer plates and screws in nine sheep. The unoperated sides acted as control. The follow-up times were 6, 12 and 24 weeks, after which radiological, mechanical and histological studies were carried out. An analysis of the implanted material was also carried out. The results showed that the SR-PLLA plates and screws were strong enough to fix the osteotomy and that the osteotomies healed mainly with callus formation. Therefore we conclude that SR-PLLA multi-layer plates and screws can be used together successfully in the fixation of mandibular osteotomies without maxillomandibular fixation. However, before they can be used in humans, the size of the plate and screws should be decreased.

The consolidation of a transverse transcondylar osteotomy of the distal rabbit femur, fixed with a self-reinforced polylactide expansion plug, was studied radiographically and mechanically. The peak shear force was assessed by stressing the osteotomy site to failure. The intact contralateral femur of the same rabbit served as a control. Fifteen rabbits were tested in groups of five animals with follow-up times of 6, 12 or 24 wk after fixation of the osteotomy. The absorbable plug, measuring 4.5 mm in diameter and 30 mm in length, had an expandable distal locking blade system. Thirteen osteotomies showed a radiographically solid bony union. The mean shear strength of the specimens was 3.5 MPa at 6 wk, 3.5 MPa at 12 wk and 4.3 MPa at 24 wk. The mean shear strength of the control distal femora was 3.6 MPa. In conclusion, the fixation properties of the newly developed absorbable expansion plug were deemed satisfactory in this experimental fracture model.

An absorbable plug for the internal fixation of fractures and osteotomies, measuring 4.5 mm in diameter and 30 mm in length, was constructed of poly-L-lactide using a self-reinforcing fibers-in-matrix manufacturing technique. To increase the rotational stability and grip of the device, the plug has deployable distal fins. The plug was used in the fixation of a transverse distal femoral osteotomy in 20 rabbits. The consolidation of the osteotomy was investigated histologically, histomorphometrically, and microradiographically in groups of five rabbits observed for three, six, 12, or 24 weeks. Fifteen osteotomies showed bony union. In five rabbits, no bridging trabeculae across the osteotomy had developed, but these rabbits belonged to the groups with the shortest follow-up times of three or six weeks. No mechanical failures of the plugs were encountered, and the short-term biocompatibility of the implant was excellent. Future clinical applications are planned.

The tissue-implant interface at a self-reinforced poly-L-lactide (SR-PLLA) expansion plug implanted in distal rabbit femoral cancellous bone was studied histologically, histomorphometrically, and microradiographically in 35 rabbits during consolidation of a transverse transcondylar osteotomy fixed with the SR-PLLA expansion plug. The absorbable plug for internal fixation of fractures and osteotomies measured 4.5 mm in diameter and 30 mm in length and had an expandable distal locking blade system. The femoral specimens were harvested in groups of 5-10 rabbits after a follow-up time of 3, 6, 12, and 24 weeks. The intact contralateral femur served as a control. Vigorous osteogenic response to the implant was already observed at 3 weeks postoperatively, and the osteoid surface fraction at 24 weeks was still significantly higher than in the unoperated contralateral femur. Incomplete union of the osteotomy seemed to result in increased fibrous tissue formation at the tissue-implant boundary. No signs of degradation of the SR-PLLA was observed within the entire follow-up period. The number of inflammatory cells at the tissue-implant interface was low. Consequently, the short-term biocompatibility of the implant was deemed acceptable. Clinical application of the expansion plug is being planned.

We studied absorbable self-reinforced poly-L-lactide screws in the fixation of osteotomies in sheep. A left olecranon osteotomy in 10 sheep was fixed with polylactide screws and in an additional 10 sheep with metallic AO cortical screws. Follow-up times were 6 and 12 weeks. 8 polylactide fixations healed and 2 failed. All metal fixations united; one of them had a fracture of the proximal fragment resulting in malposition. After killing the sheep the olecranons were radiographed and the shear strengths of the osteotomies were compared with those of the non-operated contralateral bones. After 6 weeks the mean comparative strength was 74 percent in the polylactide group and 83 percent in the metallic control group. After 12 weeks the corresponding values were 112 and 47 percent (P less than 0.05). Our study demonstrated that the mechanical weakening of fixed bone can be avoided by using absorbable polylactide screws instead of metallic screws. However, polylactide screws are not recommended for use without external support in places of high mechanical strain.