Antimicrobial and Immunomodulatory Surface-Functionalized Electrospun Membranes for Bone Regeneration

Adv Healthc Mater. 2017 May;6(10). doi: 10.1002/adhm.201601345. Epub 2017 Feb 27.

Abstract

Guided bone regeneration (GBR) is a surgical procedure utilizing occlusive membranes for providing space maintenance and enabling selective repopulation of the damaged area. While this technique is effective in regenerating bone, bacterial infiltration occurs frequently and can compromise the regenerative outcome. In this study, the authors describe the development and characterization of a GBR membrane made of medical grade polycaprolactone (mPCL) electrospun fibers with antibacterial and immunomodulatory properties. This is achieved by the immobilization of the antibiotic azithromycin into the membrane via a solvent evaporation technique leading to a sustained release of the drug over 14 d. In vitro testing shows that this controlled release of azithromycin is proficient at inhibiting the growth of Staphylococcus aureus for 14 d. Implantation of azithromycin loaded mPCL membrane in a rodent calvarial defect induces macrophage polarization toward the M2 phenotype after one week and results in significantly more bone regeneration eight weeks post-surgery. The results suggest that this antibacterial membrane should be effective at preventing infection and also impacts on the macrophage polarization enhancing bone regeneration. The drug loading technique developed in this study is simple, effective with a strong potential for clinical translation and can be applied to different types of scaffolds and implants for applications in craniofacial and orthopedics applications.

Keywords: azithromycin; bone regeneration; electrospinning; macrophage polarization.

MeSH terms

  • Animals
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Azithromycin / pharmacology
  • Biocompatible Materials / chemistry
  • Bone Regeneration / drug effects
  • Bone Regeneration / physiology*
  • Humans
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Polyesters / chemistry
  • Staphylococcus aureus / drug effects

Substances

  • Anti-Infective Agents
  • Biocompatible Materials
  • Immunologic Factors
  • Polyesters
  • polycaprolactone
  • Azithromycin