Papaioannou, Stelios; (1995) An evaluation of poly DL-Lactide-co-glycolide implants and xenogeneic bone matrix-derived growth factors on calvarial bone repair in the rabbit. Masters thesis (M.Phil), UCL (University College London).

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Abstract

The aims of this study were: (1) to extract growth factor activity from bovine bone; (2) test in vitro the feasibility of using a 50:50 poly DL-Lactide-co-glycolide polymer Molecular weight (mw) 9000 as a delivery vehicle for bone-derived growth factors; and (3) to test the performance of the bone implant material in vivo. Growth factor activity was extracted from bovine cortical bone with ETDA/Tris-HCl under non-dissociative conditions. Assays with BALB/c/3T3 and MC3T3-E1 cells demonstrated that the bone matrix extract (BMX) contained non-specific growth factor and bone morphogenetic protein activity. BMX was then incorporated into the polymer to form implant discs and incubated for 5 weeks; 60-75% of the biological activity was released during the first week. Scanning electron microscopy revealed the development of significant internal porosity by 2 weeks. Implant discs were inserted into 5 mm calvarial defects in NZW rabbits. After four weeks the discs showed advanced disintegration with little polymer matrix evident; osseous regeneration was variable, although in some animals bone with normal cancellous architecture had bridged the defect. Bone was never observed in intimate contact with the polymer matrix suggesting that the material had acted as a tissue spacer and not as an osteoconductive substrate. Non-osseous tissue comprised a vascular fibrous connective tissue with a variable number of inflammatory cells; these were MHC class II positive indicating the polymer had provoked a foreign body reaction. The implantation of polymer-BMX discs elicited a cellular and humoral immune response which had a profound inhibitory effect on osteogenesis. Histologically, the calvarial defect implanted with polymer plus BMX contained half the bone compared to polymer alone. These data suggest that although the synthetic polymer has potential as a bone graft replacement material, improvements in biocompatibility and osteoconductivity are required before contemplating their use clinically.

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