Electrospun Gelatin Fibers with a Multiple Release of Antibiotics Accelerate Dermal Regeneration in Infected Deep Burns

Macromol Biosci. 2016 Sep;16(9):1368-80. doi: 10.1002/mabi.201600108. Epub 2016 Jun 8.

Abstract

Electrospun fibers of hydrophilic polymers meet challenges in a rapid degradation of fiber matrices and discharge of antibiotics to comply with requirements of infection control as a dermal regeneration template. In the current study, a pH conversion process is initially developed to ensure fluent electrospinning, an efficient in situ cross-linking of electrospun gelatin fibers with oxidized alginate and simultaneous loading of gentamicin sulfate (GS) and hydrophobic ciprofloxacin into fibers. The dual drug-loaded fibers indicate a complete release of GS during 6 d and a sustained release of ciprofloxacin for over three weeks, and the antibiotics release indicates significant growth inhibitions on Pseudomonas aeruginosa and Staphylococcus epidermidis. The wound healing efficacy is evaluated on a deep burn model infected with 10(8) CFU of P. aeruginosa. Compared with fibers with loaded individual drugs, the concomitant release of GS and ciprofloxacin significantly reduces the bacteria numbers in wound and livers, at around 2.30 × 10(5) and 1.25 × 10(3) CFU after 3 d, respectively. The wound re-epithelization, blood vessel formation, collagen deposition, and tissue remodeling process are accelerated with a complete healing observed after 21 d. This study provides a feasible strategy to design cross-linked hydrophilic fibers with an extended drug release for biomedical applications.

Keywords: bulk cross-linking; electrospun gelatin fiber; infected deep burn; multiple release; pH conversion process.

MeSH terms

  • Alginates / chemistry
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use*
  • Burns / drug therapy*
  • Burns / microbiology*
  • Burns / pathology
  • Colony Count, Microbial
  • Cross-Linking Reagents / chemistry
  • Dermis / pathology*
  • Drug Liberation
  • Gelatin / chemistry*
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Hydrogen-Ion Concentration
  • Immunohistochemistry
  • Mice
  • NIH 3T3 Cells
  • Pseudomonas aeruginosa / drug effects
  • Regeneration / drug effects*
  • Staphylococcus epidermidis / drug effects
  • Tissue Engineering / methods*
  • Wound Healing / drug effects

Substances

  • Alginates
  • Anti-Bacterial Agents
  • Cross-Linking Reagents
  • Hexuronic Acids
  • Glucuronic Acid
  • Gelatin