Histological study of tissue reactions to epsilon-caprolactone-lactide copolymer in paste form.

In previous studies, epsilon-caprolactone-lactide copolymer in solid form has been used in experimental animals as suture material, and as a biodegradable nerve guide. The aim of the study reported here was to assess tissue reactions to epsilon-caprolactone-lactide copolymer in paste form, histologically, and to compare bone healing at the sites of implantation versus that at control sites. The other purpose of the study was to evaluate the properties of the implanted material as a filling material for bone defects. Resorption time and intensity of inflammatory reaction were also evaluated. Material was implanted into the abdominal walls and femurs of 34 rats. Follow-up times were from 2 weeks to 1 year. The results showed that epsilon-caprolactone-lactide copolymer in paste form induces a severe inflammatory reaction when placed in muscle, and moderate inflammation when implanted into bone. The resorption time was more than 1 year. Bone healing at sites of implantation was slower than at control sites.

Combining transforming growth factor-beta(1) to a bioabsorbable self-reinforced polylactide pin for osteotomy healing: an experimental study on rats.

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.

Mixture of epsilon-caprolactone-lactide copolymer and tricalcium phosphate: a histological and immunohistochemical study of tissue reactions.

In cranio-maxillofacial surgery, bone transplantation is needed for treatment of bony defects. An autograft, allograft or biomaterial can be used. Autogenous bone grafts are considered to be the best materials available, but there are some disadvantages in their use including donorsite morbidity, need for a second operative site and limited graft supply. A search for new bone-graft materials therefore remains necessary. We prepared a mixture of tricalcium phosphate (TCP), which is a resorbable, non-toxic, osteoconductive ceramic material and epsilon-caprolactone-lactide copolymer P(epsilon-CL/DL-LA), a resorbable polymer, and placed it in the dermis and in mandibular bone defects in 13 rabbits. Follow-up times were two, three, seven, eight, 12, 15 and 18 weeks, tissue reactions were assessed, histologically and immunohistochemically. Times of resorption of the material from tissues were reported. We found that the mixture caused a mild inflammatory reaction when placed in bone and severe inflammation when placed in dermis. No highly fluorescent layer of tenascin or fibronectin was found surrounding the implant area. The mixture was excellent to handle and very easy to place into bone defects. The results are promising and have led us to continue development of the mixture.

Polylactide pin with transforming growth factor beta 1 in delayed osteotomy fixation.

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.

Bone remodelling in the pores and around load bearing transchondral isoelastic porous-coated glassy carbon implants: experimental study in rabbits.

Cylinders of porous-coated glassy carbon were implanted into drill holes made through the articular surface of the medial condyle of both tibiae of ten rabbits for six and 12 weeks. Bone ingrowth and remodelling was examined by radiographic, histologic, oxytetracycline-fluorescence and microradiographic methods. Bone ingrowth into pores and load bearing implants was seen by all examination methods. Bone ingrowth occurred earlier when the pores were facing cancellous bone than cortical bone. Appositional bone formation occurred on the trabeculae a few millimetres from the interface during the early phase of remodelling at six weeks. At 12 weeks resorptive remodelling had occurred both in the surroundings and in those pores that face cancellous bone, whereas the amount of bone still increased in the pores facing cortical bone. In its porous-coated form glassy carbon functions well as a frame for ingrowing bone and it shows good osteoconductivity. Its mechanical properties are suitable for functioning as a structural bone substitute in places where the loads are mainly compressive. The difference between findings at six and 12 weeks indicated physiologic stress distribution and the adverse effects of stiff materials on bone remodelling were avoided by using this isoelastic material.

Glassy carbon implant as a bone graft substitute: an experimental study on rabbits.

The purpose of this experimental investigation was to study the incorporation of porous glassy carbon in bone. Cylinders of porous glassy carbon were implanted in drill holes in diaphyses and metaphyses of rabbits tibia for 1, 3, 6, 12 and 24 weeks. Bone ingrowth into the glassy carbon implants was examined by radiographic, histologic, fluorocrome and microradiographic methods. The material caused no pathological reaction. Tissue ingrowth into pores was seen by all examination methods. The amount of bone in the pores increases with time. The ingrowth was most distinctive in those areas where the implant was in close contact with cortical bone or trabeculae of the cancellous bone. Porous glassy carbon can be used as bone substitute, although the small size of implant available is at the present a limitation for its clinical use.

Shear strength of loaded porous-glassy-carbon/bone interface--an experimental study on rabbits.

The aim of the study was to measure the shear strength of bone/porous-glassy-carbon interface in rabbit. Glassy carbon pellets were implanted into drill holes made through the medial articular surface of the proximal tibia of 15 rabbits. Shear strengths grew statistically significantly from 1 to 6 weeks and reached a maximum of 4.6 MN/m2. Microscopical examination of the sheared surfaces revealed that at 1 and 2 weeks the shearing occurred through the tissue surrounding the implant, and at 3, 6 and 12 weeks through the porous coating of the implant. To diminish the fragility of the porous coating, its porosity should be adjusted to 40%. Results of shear strength studies on current implant materials are reviewed.

Interaction of microporous glassy carbon and living tissue.

Preliminary animal implantation tests with rats showed that microporous glassy carbon has good biocompatibility. Microporous glassy carbon is also stable and suitable for a hard biocompatible implant.