The use of BMP-2 coupled - Nanosilver-PLGA composite grafts to induce bone repair in grossly infected segmental defects

Biomaterials. 2010 Dec;31(35):9293-300. doi: 10.1016/j.biomaterials.2010.08.041. Epub 2010 Sep 22.

Abstract

Healing of contaminated/infected bone defects is a significant clinical challenge. Prevalence of multi-antibiotic resistant organisms has renewed interest in the use of antiseptic silver as an effective, but less toxic antimicrobial with decreased potential for bacterial resistance. In this study, we demonstrated that metallic nanosilver particles (with a size of 20-40nm)-poly(lactic-co-glycolic acid) (PLGA) composite grafts have strong antibacterial properties. In addition, nanosilver particles-PLGA composite grafts did not inhibit adherence, proliferation, alkaline phosphatase activity, or mineralization of ongrowth MC3T3-E1 pre-osteoblasts compared to PLGA controls. Furthermore, nanosilver particles did not affect the osteoinductivity of bone morphogenetic protein 2 (BMP-2). Infected femoral defects implanted with BMP-2 coupled 2.0% nanosilver particles-PLGA composite grafts healed in 12 weeks without evidence of residual bacteria. In contrast, BMP-2 coupled PLGA control grafts failed to heal in the presence of continued bacterial colonies. Our results indicate that nanosilver of defined particle size is bactericidal without discernable in vitro and in vivo cytotoxicity or negative effects on BMP-2 osteoinductivity, making it an ideal antimicrobial for bone regeneration in infected wounds.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / therapeutic use
  • Bone Morphogenetic Protein 2 / adverse effects
  • Bone Morphogenetic Protein 2 / chemistry*
  • Bone Morphogenetic Protein 2 / therapeutic use
  • Bone Regeneration / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Immunohistochemistry
  • Lactic Acid / adverse effects
  • Lactic Acid / chemistry*
  • Lactic Acid / therapeutic use
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Microscopy, Electron, Scanning
  • Nanocomposites / adverse effects
  • Nanocomposites / chemistry*
  • Nanocomposites / therapeutic use
  • Nanocomposites / ultrastructure
  • Nanotechnology
  • Polyglycolic Acid / adverse effects
  • Polyglycolic Acid / chemistry*
  • Polyglycolic Acid / therapeutic use
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Prostheses and Implants / adverse effects*
  • Prostheses and Implants / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Silver / chemistry*
  • Silver / therapeutic use
  • Wound Healing / drug effects*
  • X-Ray Microtomography

Substances

  • Anti-Infective Agents
  • Bone Morphogenetic Protein 2
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Silver