title: Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman Primate Model.
abstract: Antibody-mediated osseous regeneration (AMOR) has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mAbs) immobilized on a scaffold. Specifically, anti-Bone Morphogenetic Protein- (BMP-) 2 mAbs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. The present study sought to investigate the application of AMOR for repair of mandibular continuity defect in nonhuman primates. Critical-sized mandibular continuity defects were created inMacaca fascicularislocally implanted with absorbable collagen sponges (ACS) functionalized with chimeric anti-BMP-2 mAb or isotype control mAb. 2D and 3D analysis of cone beam computed tomography (CBCT) imaging demonstrated increased bone density and volume observed within mandibular continuity defects implanted with collagen scaffolds functionalized with anti-BMP-2 mAb, compared with isotype-matched control mAb. Both CBCT imaging and histologic examination demonstrated de novo bone formation that was in direct apposition to the margins of the resected bone. It is hypothesized that bone injury may be necessary for AMOR. This is evidenced by de novo bone formation adjacent to resected bone margins, which may be the source of endogenous BMPs captured by anti-BMP-2 mAb, in turn mediating bone repair.
authors.affiliation: Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tian Tan Xi Li No. 4, Beijing 100050, China; Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tian Tan Xi Li No. 4, Beijing 100050, China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tian Tan Xi Li No. 4, Beijing 100050, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Su
authors.affiliation: Laboratory for Immunoregulation and Tissue Engineering (LITE), Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Seiko
authors.identifier: 0000-0003-0716-0616
authors.initials: S
authors.lastname: Min
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Stomatological Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jianxia
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Oral & Maxillofacial Surgery, National Dental Centre, Singapore.
authors.forename: Bee Tin
authors.initials: BT
authors.lastname: Goh
authors.affiliation: Department of Oral & Maxillofacial Surgery, National Dental Centre, Singapore.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Saigo
authors.affiliation: Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA, USA.
authors.forename: Sahar
authors.identifier: 0000-0001-7965-0927
authors.initials: S
authors.lastname: Ansari
authors.affiliation: Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, CA, USA.
authors.forename: Alireza
authors.identifier: 0000-0002-1542-6202
authors.initials: A
authors.lastname: Moshaverinia
authors.affiliation: Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tian Tan Xi Li No. 4, Beijing 100050, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tian Tan Xi Li No. 4, Beijing 100050, China; Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, You An Men Wai Xi Tou Tiao No. 10, Beijing 100069, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tian Tan Xi Li No. 4, Beijing 100050, China.
authors.forename: Yi
authors.identifier: 0000-0002-4998-5547
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Tissue Engineering, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Khojasteh
authors.affiliation: Laboratory for Immunoregulation and Tissue Engineering (LITE), Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Homayoun H
authors.identifier: 0000-0002-7770-9363
authors.initials: HH
authors.lastname: Zadeh
authors.affiliation: Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tian Tan Xi Li No. 4, Beijing 100050, China; Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, You An Men Wai Xi Tou Tiao No. 10, Beijing 100069, China.
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D055396:Bone Morphogenetic Protein 2 / Q000276:immunology* / Q000627:therapeutic use; D001861:Bone Regeneration / Q000187:drug effects / Q000235:genetics; D003094:Collagen / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D008252:Macaca fascicularis; D008334:Mandible / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology; D008336:Mandibular Diseases / Q000503:physiopathology / Q000628:therapy*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014945:Wound Healing
chemical_list: D000911:Antibodies, Monoclonal; D055396:Bone Morphogenetic Protein 2; D003094:Collagen