The effect of crosslinking heparin to demineralized bone matrix on mechanical strength and specific binding to human bone morphogenetic protein-2.
Demineralized bone matrix (DBM) is a collagen-based scaffold, but its low mechanical strength and limited BMP-2 binding ability restrict its application in bone repair. It is known that heparin could be immobilized onto scaffolds to enhance their binding of growth factors with the heparin-binding domain. Here, we crosslinked heparin to DBM to increase its BMP-2 binding ability. To our surprise, the mechanical strength of DBM was also dramatically increased. The compression modulus of heparin crosslinked DBM (HC-DBM) have improved (seven-fold increased) under wet condition, which would allow the scaffolds to keep specific shapes in vivo. As expected, HC-DBM showed specific binding ability to BMP-2. Additional studies showed the bound BMP-2 exerted its function to induce cell differentiation on the scaffold. Subcutaneous implantation of HC-DBM carrying BMP-2 showed higher alkaline phosphatase (ALP) activity (2 weeks), more calcium deposition (4 and 8 weeks) and more bone formation than that of control groups. It is concluded that HC-DBM has increased mechanical intensity as well as specific BMP-2 binding ability; HC-DBM/BMP-2 enhances the osteogenesis and therefore could be an effective medical device for bone repair.
Lin
Hang
H
Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, China.
Zhao
Yannan
Y
Sun
Wenjie
W
Chen
Bing
B
Zhang
Jing
J
Zhao
Wenxue
W
Xiao
Zhifeng
Z
Dai
Jianwu
J
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001696:Biomechanical Phenomena; D001857:Bone Matrix / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D018786:Bone Substitutes / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D003432:Cross-Linking Reagents; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta / Q000378:metabolism*
C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D003432:Cross-Linking Reagents; D016212:Transforming Growth Factor beta; D006493:Heparin; D000469:Alkaline Phosphatase; D002118:Calcium