Reconstruction of the bone-bone marrow organ by osteogenin, a bone morphogenetic protein, and demineralized bone matrix in calvarial defects of adult primates

U. Ripamonti, S. S. Ma, N. S. Cunningham, L. Yeates, A Hari Reddi

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Information concerning the efficacy of osteogenin, a bone morphogenetic protein, and demineralized bone matrix in orthotopic sites in nonhuman primates is a prerequisite for potential clinical application in humans. After exposure of the calvaria, 84 cranial defects, 25 mm in diameter, were prepared in 26 adult male baboons (Papio ursinus). Defects were implanted with insoluble collagenous bone matrix (ICBM, the inactive collagenous residue after dissociative extraction of bone matrix with 4 M guanidine hydrochloride) reconstituted with osteogenin fractions isolated from baboon bone matrix by chromatography on heparin-Sepharose and hydroxyapatite- Ultrogel (Og Hep-HA) or osteogenin further purified using Sephacryl S-200 gel filtration chromatography (Og S-200). Baboon osteogenin with the highest biologic activity in a rodent bioassay, as determined by alkaline phosphatase activity, calcium content, and histologic analysis, was used for orthotopic implantation in baboons. Additional defects were implanted with baboon demineralized bone matrix (DBM) or ICBM without osteogenin as control. Defects also were grafted with corticocancellous bone harvested from the iliac crest or left ungrafted to monitor the spontaneous regeneration potential of the adult baboon calvaria. Undecalcified bone sections at 7 μm were prepared from the harvested specimens 30 and 90 days after surgery. Histomorphometry demonstrated that Og S-200 induced copious amounts of bone and osteoid as early as day 30 (P < 0.01 versus ICBM, autogenous grafts and untreated defects). At day 90, in implants of Og S-200, Og Hep-HA, and DBM, bone and marrow formation was extensive, culminating in complete regeneration of the craniotomies. In implants of DBM, bone formed with an intervening phase of cartilage development. This provides the phenotypic evidence of endochondral bone differentiation by induction in defects of membranous calvarial bone in adult primates. These results establish the potential therapeutic application of osteogenin and demineralized bone matrix for the architectural reconstruction of the bone-bone marrow organ in humans.

Original languageEnglish (US)
Pages (from-to)27-36
Number of pages10
JournalPlastic and Reconstructive Surgery
Volume91
Issue number1
StatePublished - 1993
Externally publishedYes

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Bone Morphogenetic Protein 3
Bone Morphogenetic Proteins
Bone Matrix
Primates
Papio
Bone Marrow
Bone and Bones
Skull
Regeneration
Papio ursinus
Craniotomy
Guanidine
Durapatite
Ambulatory Surgical Procedures
Osteogenesis
Biological Assay
Cartilage
Gel Chromatography
Alkaline Phosphatase
Chromatography

ASJC Scopus subject areas

  • Surgery

Cite this

Reconstruction of the bone-bone marrow organ by osteogenin, a bone morphogenetic protein, and demineralized bone matrix in calvarial defects of adult primates. / Ripamonti, U.; Ma, S. S.; Cunningham, N. S.; Yeates, L.; Reddi, A Hari.

In: Plastic and Reconstructive Surgery, Vol. 91, No. 1, 1993, p. 27-36.

Research output: Contribution to journalArticle

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