Biocompatible Hybrid Organic/Inorganic Microhydrogels Promote Bacterial Adherence and Eradication in Vitro and in Vivo

Nano Lett. 2020 Mar 11;20(3):1590-1597. doi: 10.1021/acs.nanolett.9b04290. Epub 2020 Feb 17.

Abstract

Self-assembling peptides and proteins have the potential to serve as multifunctional building blocks for the generation of versatile materials for a wide range of biomedical applications. In particular, supramolecular hydrogels comprised of self-assembled protein nanofibrils, have been used in contexts ranging from tissue engineering to drug delivery. Due to the rapid emergence of multidrug resistant bacteria, development of biomaterials with intrinsic antimicrobial properties has been continuously increasing. Here, we describe hybrid organic/inorganic nanofibrillar silk microgels decorated with silver nanoparticles that display potent antimicrobial activity in vitro and in vivo and are able to adhere bacterial cells to their surfaces while subsequently eradicating them, through a two-step mechanism of action. Importantly, in contrast to treatments involving conventional silver, these silk-silver microgels are nonhemolytic and noncytotoxic toward mammalian cell lines. Finally, we show that these hybrid microgels display substantial efficacy as topical antimicrobial agents in a murine model of surgical site infections.

Keywords: Antibacterial materials; Biomaterials; Microhydrogels; Organic/inorganic interfaces; Regenerated silk fibroin; Self-assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Anti-Infective Agents* / chemistry
  • Anti-Infective Agents* / pharmacology
  • Bacteria / growth & development*
  • Bacterial Adhesion / drug effects*
  • Bacterial Infections* / drug therapy
  • Bacterial Infections* / metabolism
  • Bacterial Infections* / pathology
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Materials Testing
  • Metal Nanoparticles* / chemistry
  • Metal Nanoparticles* / therapeutic use
  • Mice
  • Nanofibers* / chemistry
  • Nanofibers* / therapeutic use
  • Sheep
  • Silk* / chemistry
  • Silk* / pharmacology
  • Silver* / chemistry
  • Silver* / pharmacology

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Hydrogels
  • Silk
  • Silver