title: Application of AMOR in craniofacial rabbit bone bioengineering.
abstract: Endogenous molecular and cellular mediators modulate tissue repair and regeneration. We have recently described antibody mediated osseous regeneration (AMOR) as a novel strategy for bioengineering bone in rat calvarial defect. This entails application of anti-BMP-2 antibodies capable of in vivo capturing of endogenous osteogenic BMPs (BMP-2, BMP-4, and BMP-7). The present study sought to investigate the feasibility of AMOR in other animal models. To that end, we examined the efficacy of a panel of anti-BMP-2 monoclonal antibodies (mAbs) and a polyclonal Ab immobilized on absorbable collagen sponge (ACS) to mediate bone regeneration within rabbit calvarial critical size defects. After 6 weeks, de novo bone formation was demonstrated by micro-CT imaging, histology, and histomorphometric analysis. Only certain anti-BMP-2 mAb clones mediated significant in vivo bone regeneration, suggesting that the epitopes with which anti-BMP-2 mAbs react are critical to AMOR. Increased localization of BMP-2 protein and expression of osteocalcin were observed within defects, suggesting accumulation of endogenous BMP-2 and/or increased de novo expression of BMP-2 protein within sites undergoing bone repair by AMOR. Considering the ultimate objective of translation of this therapeutic strategy in humans, preclinical studies will be necessary to demonstrate the feasibility of AMOR in progressively larger animal models.
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA, USA ; Department of Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
authors.forename: Marcelo
authors.identifier: 0000-0003-4906-7698
authors.initials: M
authors.lastname: Freire
authors.affiliation: Department of Orthodontics, School of Dentistry, Seoul National University, Jongno-gu, Seoul 110-749, Republic of Korea.
authors.forename: Jeong-Ho
authors.identifier: 0000-0003-4529-7218
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Department of Periodontology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea.
authors.forename: Young Deok
authors.initials: YD
authors.lastname: Chee
authors.affiliation: Department of Oral Biochemistry, School of Dentistry, Chosun University, Gwangju, Republic of Korea.
authors.forename: Joong-Ki
authors.initials: JK
authors.lastname: Kook
authors.affiliation: Department of Periodontology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea.
authors.forename: Hyung-Keun
authors.identifier: 0000-0002-4585-0477
authors.initials: HK
authors.lastname: You
authors.affiliation: Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA ; Laboratory for Immunoregulation & Tissue Engineering, Herman Ostrow School of Dentistry, University of Southern California, 925 West 34th Street, Los Angeles, CA 90089, USA.
authors.forename: Homayoun H
authors.initials: HH
authors.lastname: Zadeh
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D057005:Bioengineering; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*; D001861:Bone Regeneration / Q000276:immunology*; D006801:Humans; D015675:Osteocalcin / Q000096:biosynthesis / Q000276:immunology; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D054457:Tissue Scaffolds
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D015675:Osteocalcin