U. Ripamonti et al., EXPRESSION OF THE OSTEOGENIC PHENOTYPE IN POROUS HYDROXYAPATITE IMPLANTED EXTRASKELETALLY IN BABOONS, Matrix, 13(6), 1993, pp. 491-502
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.