title: The osteogenic effect of bone morphogenetic protein-2 on the collagen scaffold conjugated with antibodies.
abstract: Considerable research has been focused on the exploration of bone morphogenetic protein-2 (BMP(2)) delivery vehicles for achieving prolonged availability and maintaining efficient local concentration at the bone injury sites. In this study, heterobifunctional cross-linkers Sulfo-SMCC and cyclic thioimidate compound Traut's Reagent were used to conjugate monoclonal polyhistidine antibody on collagen scaffold demineralized bone matrix (DBM) to create specific binding between BMP(2) containing six histidines tag (His-BMP(2)) and DBM. According to the optimized cross-linking reagent concentration, more polyhistidine antibodies conjugated on DBM with 5mg/ml Traut's Reagent and 25ug/ml Sulfo-SMCC than physical adsorption. Monoclonal antibodies conjugated DBM (MAbs-DBM) could bind more His-BMP(2) than DBM and achieved controlled release in vitro. The alkaline phophatase (AP) activity of C2C12 cells on MAbs-DBM indicated that His-BMP(2) retained on MAbs-DBM preserved the function to induce osteogenic differentiation. His-BMP(2)/MAbs-DBM induced more ectopic bone formation (AP activity assay and histochemistry stain) than control group after subcutaneous implantation. The results demonstrated that antibody-collagen system could be useful for maintaining higher local therapy concentration of growth factors at the injury sites.
authors: Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China.
authors: Yannan
authors: Y
authors: Zhao
authors: Jing
authors: J
authors: Zhang
authors: Xia
authors: X
authors: Wang
authors: Bin
authors: B
authors: Chen
authors: Zhifeng
authors: Z
authors: Xiao
authors: Chunying
authors: C
authors: Shi
authors: Zhanliang
authors: Z
authors: Wei
authors: Xianglin
authors: X
authors: Hou
authors: Qiangbin
authors: Q
authors: Wang
authors: Jianwu
authors: J
authors: Dai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D001857:Bone Matrix / Q000737:chemistry*; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D003094:Collagen / Q000737:chemistry*; D004343:Drug Implants; D004797:Enzyme-Linked Immunosorbent Assay; D006639:Histidine / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D012995:Solubility
chemical_list: D000911:Antibodies, Monoclonal; D055396:Bone Morphogenetic Protein 2; D004343:Drug Implants; D011993:Recombinant Fusion Proteins; D006639:Histidine; D003094:Collagen