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BIOACTIVE BONE SUBSTITUTES – FROM SCIENCE TO SURGERY



Abstract

Osteogenic proteins (OPs), also referred to as bone morphogenetic proteins (BMPs), are a family of bone-matrix polypeptides isolated from a variety of mammalian species. These proteins are members of the transforming growth factors-beta superfamily of molecules that contain a highly conserved 7 cysteine transforming growth factor domain in their C-termini. Implantation of osteogenic proteins induce a sequence of cellular events that leads to the formation of new bone.

In preclinical studies, the implantation of recombinantly produced human osteogenic protein-1 (OP-1, also referred to as BMP-7) in conjunction with bovine bone derived Type 1 collagen or various nonproteinaceous biodegradable carriers into surgically created, critical size diaphyseal segmental defects resulted in the regeneration of new bone that was fully functional biologically and biomechanically. Injection of an OP-1 solution into a fresh fracture model accelerated the bone repair process compared with control fracture healing. Significantly increased biomechanical strength was the result of greater and earlier new bone formation. Further study has demonstrated that OP-1 can be used as a bone graft substitute to promote spinal fusion, aid in the incorporation of metal implants, and improve the performance of autograft and allograft bone. OP-1 has also shown promise as an agent for the repair of osteochondral defects.

Clinical study of the OP-1 device for the treatment of tibial nonunion fractures has shown healing characteristics similar to that obtained with autogenous iliac crest bone graft. The randomized, prospective clinical evaluation included 30 patients with 31 tibal nonunion fractures. The mean time from injury was 27.2 months (minimum 9 months). All patients were treated with reamed intramedullary rods. At the 9 month evaluation 14 of 16 OP-1 and 14 of 15 autograft treated fractures were clinically and radiographically healed. Advantages of OP-1 included no donor site complications, less blood loss, an a shorter operative time.

The abstracts were prepared by Professor Jegan Krishnan. Correspondence should be addressed to him at the Flinders Medical Centre, Bedford Park 5047, Australia.