Local delivery of bone morphogenetic proteins in primates using a reconstituted basement membrane gel:: tissue engineering with Matrigel

BONE MORPHOGENETIC AND OSTEOGENIC proteins (BMPs/OPs) have the striking ability to induce de novo bone formation and have advanced our understanding of cell differentiation and the induction of tissue morphogenesis.(1-4) Osteoblastic differentiation and the induction of bone formation are controlled by the BMPs/OPs, members of the transforming growth factor-beta (TGF-beta) supergene family.(1-4) These soluble signals must be reconstituted with an insoluble substratum that triggers the bone differentiation cascade, as shown in non-human primates and humans.(1-3,10) To achieve this, the basement membrane Matrigel was found to deliver naturally-derived BMPs/OPs and recombinantly produced human osteogenic protein-1 (hOP-1). We have used Matrigel, reconstituted with BMPs/OPs, for a novel localized treatment of systemic bone loss in baboons (Papio ursinus). The bone mineral density of the lumbar vertebrae of ovariectomized baboons was significantly affected by oestrogen depletion. Histomorphometric data on the iliac crest biopsies showed that bone was permanently lost 36 months after ovariectomy. Injection of BMPs/OPs into the lumbar vertebrae 3 and 4 of two animals, using an X-ray image intensifier for guidance, was successfully performed for the first time on primates. Bone mineral density, as measured by dual photon X-ray absorptiometry, subsequently increased. Although new bone formation in the vertebrae was not uniform, it was reproducible, This method may therefore prove to be valuable for the treatment of systemic bone loss by localized bone induction in clinical contexts.