Three-dimensional bioprinted cell-adaptive hydrogel with anisotropic micropores for enhancing skin wound healing

Int J Biol Macromol. 2024 Nov;280(Pt 4):136106. doi: 10.1016/j.ijbiomac.2024.136106. Epub 2024 Sep 27.

Abstract

Engineered matrices with aligned microarchitectures are pivotal in regulating the fibroblast-to-myofibroblast transition, a critical process for wound healing and scar reduction. However, developing a three-dimensional (3D) aligned matrix capable of effectively controlling this transition remains challenging. Herein, we developed a cell-adaptive hydrogel with highly oriented microporous structures, fabricated through bioprinting of thermo/ion/photo-crosslinked gelatin methacrylate/sodium alginate (GelMA/SA) incorporating shear-oriented polyethylene oxide (PEO) filler. The synergistic interactions among GelMA, PEO, and SA yield a homogeneous mixture conducive to the printing of biomimetic 3D constructs with anisotropic micropores. These anisotropic micropores, along with the biochemical cues provided by the GelMA/PEO/SA scaffolds, enhance the oriented spreading and organization of fibroblasts. The resultant spread and aligned cellular morphologies promote the transition of fibroblasts into myofibroblasts. By co-culturing human keratinocytes on the engineered dermal layer, we successfully create a bilayer skin construct, wherein the keratinocytes establish tight junctions accompanied by elevated expression of cytokeratin-14, while the fibroblasts display a highly spread morphology with increased fibronectin expression. The printed hydrogels accelerate full-thickness wound closure by establishing a bioactive microenvironment that mitigate inflammation and stimulate angiogenesis, myofibroblast transition, and extracellular matrix remodeling. This anisotropic hydrogel demonstrates substantial promise for applications in skin tissue engineering.

Keywords: Myofibroblast; Oriented micropores; Wound repair.

MeSH terms

  • Alginates / chemistry
  • Animals
  • Anisotropy
  • Bioprinting* / methods
  • Fibroblasts* / cytology
  • Fibroblasts* / drug effects
  • Humans
  • Hydrogels* / chemistry
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Porosity
  • Printing, Three-Dimensional*
  • Skin*
  • Tissue Engineering* / methods
  • Tissue Scaffolds* / chemistry
  • Wound Healing* / drug effects

Substances

  • Hydrogels
  • Alginates