Vancomycin-bearing synthetic bone graft delivers rhBMP-2 and promotes healing of critical rat femoral segmental defects

Clin Orthop Relat Res. 2014 Dec;472(12):4015-23. doi: 10.1007/s11999-014-3841-1. Epub 2014 Aug 7.


Background: Bone grafts simultaneously delivering therapeutic proteins and antibiotics may be valuable in orthopaedic trauma care. Previously, we developed a poly(2-hydroxyethyl methacrylate)-nanocrystalline hydroxyapatite (pHEMA-nHA) synthetic bone graft that, when preabsorbed with 400-ng rhBMP-2/7, facilitated the functional repair of critical-size rat femoral defects. Recently, we showed that pHEMA-nHA effectively retains/releases vancomycin and rhBMP-2 in vitro. The success of such a strategy requires that the incorporation of vancomycin does not compromise the structural integrity of the graft nor its ability to promote bone healing.

Questions/purposes: (1) To evaluate the ability of pHEMA-nHA-vancomycin composites in combination with 3-µg rhBMP-2 to repair 5 mm rat femoral segmental defects, and (2) To determine if the encapsulated vancomycin impairs the graft/rhBMP-2-assisted bone repair.

Methods: pHEMA-nHA-vancomycin, pHEMA-nHA, or collagen sponge control with/without 3-µg rhBMP-2 were press-fit in 5 mm femoral defects in SASCO-SD male rats (289-300 g). Histology, microcomputed tomography, and torsion testing were performed on 8- and 12-week explants to evaluate the extent and quality of repair. The effect of vancomycin on the temporal absorption of endogenous BMP-2 and stromal cell-derived factor-1 was evaluated by immunohistochemistry. These factors are important for bone healing initiation and stem cell recruitment, respectively.

Results: Partial bridging of the defect with bony callus by 12 weeks was observed with pHEMA-nHA-vancomycin without rhBMP-2 while full bridging with substantially mineralized callus and partial restoration of torsional strength was achieved with 3-µg rhBMP-2. The presence of vancomycin changed the absorption patterns of endogenous proteins on the grafts, but did not appear to substantially compromise graft healing.

Conclusions: The composite pHEMA-nHA-vancomycin preabsorbed with 3-µg rhBMP-2 promoted repair of 5 mm rat femoral segmental defects. With the sample sizes applied, vancomycin encapsulation did not appear to have a negative effect on bone healing.

Clinical relevance: pHEMA-nHA-vancomycin preabsorbed with rhBMP-2 may be useful in the repair of critical-size long bone defects prone to infections.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Biomechanical Phenomena
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Substitutes*
  • Bone Transplantation / instrumentation*
  • Bone Transplantation / methods
  • Chemokine CXCL12 / metabolism
  • Coated Materials, Biocompatible*
  • Disease Models, Animal
  • Femoral Fractures / diagnostic imaging
  • Femoral Fractures / metabolism
  • Femoral Fractures / physiopathology
  • Femoral Fractures / therapy*
  • Femur / diagnostic imaging
  • Femur / drug effects*
  • Femur / metabolism
  • Femur / physiopathology
  • Femur / surgery*
  • Fracture Healing / drug effects*
  • Hydroxyapatites / chemistry*
  • Male
  • Osseointegration / drug effects
  • Polymethacrylic Acids / chemistry*
  • Prosthesis Design
  • Rats
  • Recombinant Proteins / administration & dosage
  • Time Factors
  • Torsion, Mechanical
  • Vancomycin / administration & dosage*
  • X-Ray Microtomography


  • Anti-Bacterial Agents
  • BMP2 protein, human
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Substitutes
  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Coated Materials, Biocompatible
  • Hydroxyapatites
  • Polymethacrylic Acids
  • Recombinant Proteins
  • poly(2-hydroxyethyl methacrylate)-nanocrystalline hydroxyapatite
  • Vancomycin