Homogeneous osteogenesis and bone regeneration by demineralized bone matrix loading with collagen-targeting bone morphogenetic protein-2.
Considerable research has been focused on the development of bone morphogenetic protein-2 (BMP-2) delivery system for homologous and efficient bone regeneration. The aim of the present study was to develop a collagen-based targeting bone repair system. A collagen-binding domain (CBD) was added to the N-terminal of native BMP-2 to allow it bind to collagen specifically. We showed that the collagen-binding bone morphogenetic protein-2 (named bone morphogenetic protein2-h, BMP2-h) had maintained the full biological activity as compared to rhBMP2 lacking the CBD. In vitro functional study also demonstrated that collagen matrix could maintain higher bioactivity of BMP2-h than native BMP-2. When demineralized bone matrix (DBM) impregnated with BMP2-h was implanted subcutaneously in rats, homogeneous bone formation was observed. Moreover, in a rabbit mandible defect model, surgical implantation of collagen matrix loaded with BMP2-h exhibited remarkable osteoinductive properties and excellent homogeneous bone formation. Our studies suggested that this novel collagen-based BMP-2 targeting bone repair system induced better bone formation not only in quantity but also in quality. Similar approaches may also be used for the repair of other tissue injuries.
Chen
Bing
B
Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing 100080, China.
Lin
Hang
H
Wang
Jianhua
J
Zhao
Yannan
Y
Wang
Bin
B
Zhao
Wenxue
W
Sun
Wenjie
W
Dai
Jianwu
J
D000818:Animals; D018775:Bone Demineralization Technique; D001857:Bone Matrix / Q000737:chemistry*; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D001861:Bone Regeneration / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry; D017102:Fracture Healing / Q000187:drug effects; D008297:Male; D008337:Mandibular Fractures / Q000188:drug therapy* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D016896:Treatment Outcome
C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D016212:Transforming Growth Factor beta; D003094:Collagen