Functional restoration of critically sized segmental defects with bone morphogenetic protein-2 and heparin treatment

Clin Orthop Relat Res. 2011 Nov;469(11):3111-7. doi: 10.1007/s11999-011-2012-x.


Background: Bone defects and fracture nonunions remain a substantial challenge for clinicians. Grafting procedures are limited by insufficient volume and donor site morbidity. As an alternative, biomaterial scaffolds functionalized through incorporation of growth factors such as bone morphogenetic proteins (BMPs) have been developed and appear to regenerate the structure and function of damaged or degenerated skeletal tissue.

Objectives/purposes: Our objectives were therefore to determine whether: (1) the addition of heparin alone to collagen scaffolds sufficed to promote bone formation in vivo; (2) collagen-heparin scaffold improved BMP-mediated bone regeneration; and (3) precomplexed heparin and BMP-2 delivered on collagen scaffold could restore long bone biomechanical strength.

Methods: We created bilateral surgical defects in the femora of 20 rats and filled the defects with PCL scaffolds with one of five treatments: collagen matrix (n = 5), collagen/heparin matrix (n = 7), collagen matrix + BMP-2 (n = 9), collagen/heparin matrix + BMP-2 (n = 9), or collagen matrix + BMP-2/heparin complex (n = 9). Bone formation was observed with radiographs and micro-CT analysis and biomechanical testing was used to assess strength.

Results: The addition of heparin alone to collagen did not promote bone ingrowth and the addition of heparin to collagen did not improve BMP-mediated bone regeneration. Delivery of precomplexed BMP-2 and heparin in a collagen matrix resulted in new bone formation with mechanical properties similar to those of intact bone.

Clinical relevance: Our findings suggest delivery of precomplexed BMP-2 and heparin may be an advantageous strategy for treatment of clinically challenging bone defects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone Regeneration / drug effects*
  • Bone Regeneration / physiology
  • Collagen / chemistry
  • Collagen / pharmacology
  • Compressive Strength
  • Disease Models, Animal
  • Drug Combinations
  • Femur / drug effects
  • Femur / injuries
  • Femur / physiopathology
  • Fracture Healing / drug effects*
  • Fracture Healing / physiology
  • Heparin / pharmacology*
  • Osteogenesis / drug effects*
  • Osteogenesis / physiology
  • Osteotomy / methods
  • Rats
  • Tissue Engineering
  • Tissue Scaffolds / chemistry


  • Bone Morphogenetic Protein 2
  • Drug Combinations
  • Heparin
  • Collagen