α-Lactalbumin based scaffolds for infected wound healing and tissue regeneration

Int J Pharm. 2024 Sep 30:663:124578. doi: 10.1016/j.ijpharm.2024.124578. Epub 2024 Aug 15.

Abstract

Interruption of wound healing by multi-drug resistant-bacterial infection is a harmful issue for the worldwide health care system, and conventional treatment approaches may not resolve this issue due to antimicrobial resistance. So, there is an unmet need to develop scaffolds with intrinsic wound healing properties to combat bacterial-infected wounds. Inspired by the α-lactalbumin's (Lalb's) ability to promote collagen synthesis, we herein electrospun Lalb with cephalexin (CPL) and epigallocatechin (EP) to produce nanofibers (CE-Lalb NFs) to solve this issue. The CE-Lalb NFs were prepared using the electrospinning technique and subjected to physicochemical characterizations, in vitro, and in vivo assessments. The CE-Lalb NFs promoted fibroblast migration, proliferation, and collagen synthesis, while CPL/EP annihilated MRSA and E. coli infections. Physicochemical characterizations proved the successful fabrication and doping of CE-Lalb NFs. Antimicrobial assays and fractional inhibitory concentration index (FICI) declared synergistic antibacterial activity of CE-Lalb NFs against MRSA and E. coli. The in vivo and immunohistochemical data evidenced its exceptional potential for wound healing, promoting growth factor, collagen synthesis, and reduced scar formation. The presence of mature collagen, fewer inflammatory cytokines, increased expression of blood vessels, and low expression of IL-6 at the wound site support in vitro and in vivo results. In our view, the tailored scaffold is the next step for personalized wound dressings that could meet patients with infected wounds' unmet needs by the subscription of noninvasive and easily navigable therapeutic options.

Keywords: Cephalexin; Electrospun nanofibers; Epigallocatechin; Infected wounds; α-lactalbumin.

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives
  • Catechin / chemistry
  • Catechin / pharmacology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cephalexin / administration & dosage
  • Cephalexin / chemistry
  • Cephalexin / pharmacology
  • Collagen
  • Escherichia coli / drug effects
  • Escherichia coli Infections / drug therapy
  • Fibroblasts / drug effects
  • Humans
  • Lactalbumin* / chemistry
  • Lactalbumin* / pharmacology
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Mice
  • Nanofibers / chemistry
  • Rats
  • Regeneration / drug effects
  • Staphylococcal Infections / drug therapy
  • Tissue Scaffolds / chemistry
  • Wound Healing* / drug effects

Substances

  • Anti-Bacterial Agents
  • Lactalbumin
  • Collagen
  • Catechin
  • Cephalexin