The effect of crosslinking heparin to demineralized bone matrix on mechanical strength and specific binding to human bone morphogenetic protein-2

Biomaterials. 2008 Mar;29(9):1189-97. doi: 10.1016/j.biomaterials.2007.11.032.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Biocompatible Materials / chemistry
  • Biomechanical Phenomena
  • Bone Matrix / chemistry*
  • Bone Matrix / drug effects
  • Bone Matrix / physiology*
  • Bone Matrix / ultrastructure
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / metabolism*
  • Bone Substitutes / chemistry*
  • Calcium / metabolism
  • Cattle
  • Cross-Linking Reagents
  • Heparin / chemistry*
  • Heparin / pharmacology
  • Humans
  • Male
  • Materials Testing
  • Microscopy, Electron, Scanning
  • Osteogenesis
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Engineering
  • Transforming Growth Factor beta / metabolism*

Substances

  • BMP2 protein, human
  • Biocompatible Materials
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Bone Substitutes
  • Cross-Linking Reagents
  • Transforming Growth Factor beta
  • Heparin
  • Alkaline Phosphatase
  • Calcium