EXPRESSION OF THE OSTEOGENIC PHENOTYPE IN POROUS HYDROXYAPATITE IMPLANTED EXTRASKELETALLY IN BABOONS

A porous hydroxyapatite was used as a morphogenetic matrix to study ea rly tissue formation preceding the morphogenesis of bone in extraskele tal sites of the baboon (Papio ursinus). Porous hydroxyapatites, obtai ned by hydrothermal conversion of the calcium carbonate exoskeleton of coral, were implanted extraskeletally in 16 baboons. Specimens were h arvested at days 30, 60 and 90, and processed to obtain decalcified se ctions for histomorphometry, and undecalcified sections for enzyme his tochemical demonstration of alkaline phosphatase, immunohistochemical demonstration of laminin and type I collagen, and for comparative hist ologic analysis. At day 30, the tissue that invaded the porous spaces showed mesenchymal condensations at the hydroxyapatite interface, and prominent vascular penetration. Collagen type I staining was localized within mesenchymal condensations. Bone had not formed in any specimen harvested at day 30. At days 30 and 60, alkaline phosphatase staining was initially localized in the invading vasculature, and subsequently found in cellular condensations prior to their transformation into bo ne, and in capillaries close to cellular condensations. Laminin staini ng was localized around invading capillaries adjacent to and within me senchymal condensations, and in capillaries in direct contact with the hydroxyapatite. Bone had formed by day 60; cartilage, however, was ne ver observed. By day 90, bone formation within the porous spaces was o ften extensive. Goldner's trichrome stain and fluorescence microscopy of tetracycline-labeled specimens demonstrated nascent mineralization within condensations during initial bone morphogenesis. Coating the hy droxyapatite with collagen type I prepared from baboon bone did not in crease the amount of bone formation. In this hydroxyapatite-induced os teogenesis model in primates, vascular invasion and bone differentiati on appear to be accompanied by a specific temporal sequence of alkalin e phosphatase expression. The differentiation of osteogenic cells in d irect apposition to the hydroxyapatite suggests that this substratum m ay act as a solid state matrix for adsorption and controlled release o f endogenously-produced bone morphogenetic proteins. The porous hydrox yapatite, as used in this bioassay in primates, may be an appropriate delivery system for bone morphogenetic proteins for the controlled ini titiation of therapeutic osteogenesis.