Injectable bioadhesive hydrogels with innate antibacterial properties

Nat Commun. 2014 Jun 24:5:4095. doi: 10.1038/ncomms5095.

Abstract

Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde and branched polyethylenimine. These adhesives kill both Gram-negative and Gram-positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5 wt% oxidized dextran and 6.9 wt% polyethylenimine sets within seconds forming a mechanically rigid (~1,700 Pa) gel offering a maximum adhesive stress of ~2.8 kPa. A murine infection model showed that the adhesive is capable of killing Streptococcus pyogenes introduced subcutaneously at the bioadhesive's surface, with minimal inflammatory response. The adhesive was also effective in a cecal ligation and puncture model, preventing sepsis and significantly improving survival. These bioadhesives represent novel, inherently antibacterial materials for wound-filling applications.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects*
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology*
  • Mice, Inbred BALB C
  • Streptococcal Infections / drug therapy*
  • Streptococcal Infections / microbiology
  • Streptococcus pyogenes / drug effects
  • Streptococcus pyogenes / physiology

Substances

  • Anti-Bacterial Agents
  • Hydrogel, Polyethylene Glycol Dimethacrylate