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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 in Macaca fascicularis locally 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.
PMID
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Authors

Mayor MeshTerms

Tissue Engineering

Keywords
Journal Title biomed research international
Publication Year Start




PMID- 28401163
OWN - NLM
STAT- MEDLINE
DA  - 20170412
DCOM- 20170428
LR  - 20170428
IS  - 2314-6141 (Electronic)
VI  - 2017
DP  - 2017
TI  - Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody
      Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman
      Primate Model.
PG  - 8094152
LID - 10.1155/2017/8094152 [doi]
AB  - 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 in Macaca fascicularis locally
      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.
FAU - Xie, Yilin
AU  - Xie Y
AD  - 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.
FAU - Su, Yingying
AU  - Su Y
AD  - 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.
FAU - Min, Seiko
AU  - Min S
AUID- ORCID: 0000-0003-0716-0616
AD  - Laboratory for Immunoregulation and Tissue Engineering (LITE), Ostrow School of
      Dentistry, University of Southern California, Los Angeles, CA, USA.
FAU - Tang, Jianxia
AU  - Tang J
AD  - Department of Oral and Maxillofacial Surgery, Xiangya Stomatological Hospital,
      Central South University, Changsha, Hunan, China.
FAU - Goh, Bee Tin
AU  - Goh BT
AD  - Department of Oral & Maxillofacial Surgery, National Dental Centre, Singapore.
FAU - Saigo, Leonardo
AU  - Saigo L
AD  - Department of Oral & Maxillofacial Surgery, National Dental Centre, Singapore.
FAU - Ansari, Sahar
AU  - Ansari S
AUID- ORCID: 0000-0001-7965-0927
AD  - Division of Growth and Development, School of Dentistry, University of
      California, Los Angeles, CA, USA.
FAU - Moshaverinia, Alireza
AU  - Moshaverinia A
AUID- ORCID: 0000-0002-1542-6202
AD  - Division of Advanced Prosthodontics, School of Dentistry, University of
      California, Los Angeles, CA, USA.
FAU - Zhang, Chunmei
AU  - Zhang C
AD  - 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.
FAU - Wang, Jinsong
AU  - Wang J
AD  - 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.
FAU - Liu, Yi
AU  - Liu Y
AUID- ORCID: 0000-0002-4998-5547
AD  - 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.
FAU - Khojasteh, Arash
AU  - Khojasteh A
AD  - Department of Tissue Engineering, School of Advanced Technologies in Medicine,
      Shahid Beheshti University of Medical Sciences, Tehran, Iran.
FAU - Zadeh, Homayoun H
AU  - Zadeh HH
AUID- ORCID: 0000-0002-7770-9363
AD  - Laboratory for Immunoregulation and Tissue Engineering (LITE), Ostrow School of
      Dentistry, University of Southern California, Los Angeles, CA, USA.
FAU - Wang, Songlin
AU  - Wang S
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20170316
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/immunology/*therapeutic use
MH  - Bone Morphogenetic Protein 2/*immunology/therapeutic use
MH  - Bone Regeneration/drug effects/genetics
MH  - Collagen/therapeutic use
MH  - Disease Models, Animal
MH  - Humans
MH  - Macaca fascicularis
MH  - Mandible/drug effects/*growth & development/pathology
MH  - Mandibular Diseases/physiopathology/*therapy
MH  - Osteogenesis/drug effects/genetics
MH  - *Tissue Engineering
MH  - Tissue Scaffolds
MH  - Wound Healing
PMC - PMC5376406
COI - The authors declare no potential conflict of interests with respect to the
      authorship and/or publication of this article.
EDAT- 2017/04/13 06:00
MHDA- 2017/04/13 06:00
CRDT- 2017/04/13 06:00
PHST- 2016/10/24 [received]
PHST- 2017/01/05 [revised]
PHST- 2017/01/19 [accepted]
AID - 10.1155/2017/8094152 [doi]
PST - ppublish
SO  - Biomed Res Int. 2017;2017:8094152. doi: 10.1155/2017/8094152. Epub 2017 Mar 16.

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