Periodontal tissue regeneration by combined applications of recombinant human osteogenic protein-1 and bone morphogenetic protein-2. A pilot study in Chacma baboons (Papio ursinus).
Native and recombinant human bone morphogenetic/osteogenic proteins (BMPs/ OPs) singly initiate bone induction in vivo. The finding of synchronous but spatially different BMPs/OPs expression during periodontal tissue morphogenesis suggests novel therapeutic approaches using morphogen combinations based on recapitulation of embryonic development. Twelve furcation defects prepared in the first and second mandibular molars of three adult baboons (Papio ursinus) were used to assess whether qualitative histological aspects of periodontal tissue regeneration could be enhanced and tissue morphogenesis modified by combined or single applications of recombinant hOP-1 and hBMP-2. Doses of BMPs/OPs were 100 microg of each protein per 1 g of insoluble collagenous bone matrix as carrier. Approximately 200 mg of carrier matrix was used per furcation defect. Undecalcified sections cut for histological analysis 60 d after healing of hOP-1-treated specimens showed substantial cementogenesis with scattered remnants of the collagenous carrier. hBMP-2 applied alone induced greater amounts of mineralized bone and osteoid when compared to hOP-1 alone or to combined morphogen applications. Combined applications of hOP-1 and hBMP-2 did not enhance alveolar bone regeneration or new attachment formation over and above the single applications of the morphogens. The results of this study, which is the first to attempt to address the structure-activity relationship amongst BMP/OP family members, indicate that tissue morphogenesis induced by hOP-1 and hBMP-2 is qualitatively different when the morphogens are applied singly, with hOP-1 inducing substantial cementogenesis. hBMP-2 treated defects, on the other hand, showed limited cementum formation but a temporal enhancement of alveolar bone regeneration and remodelling. The demonstration of therapeutic mosaicism in periodontal regeneration will require extensive testing of ratios and doses of recombinant morphogen combinations for optimal tissue engineering in clinical contexts.
Ripamonti
U
U
Bone Research Unit, Medical Research Council/University of the Witwatersrand, Medical School, Johannesburg, South Africa. 177ripa@chiron.wits.ac.za
Crooks
J
J
Petit
J C
JC
Rueger
D C
DC
D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001857:Bone Matrix / Q000187:drug effects / Q000473:pathology; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000737:chemistry / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D003739:Dental Cementum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004337:Drug Carriers; D017823:Furcation Defects / Q000188:drug therapy*; D006801:Humans; D016014:Linear Models; D008297:Male; D008963:Molar; D009024:Morphogenesis / Q000187:drug effects; D010215:Papio; D010519:Periodontium / Q000187:drug effects* / Q000473:pathology; D010865:Pilot Projects; D011994:Recombinant Proteins; D012038:Regeneration / Q000187:drug effects*; D013223:Statistics as Topic; D013329:Structure-Activity Relationship; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000627:therapeutic use*; D014945:Wound Healing
C525718:BMP2 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2