Biologically inspired bioactive hydrogels for scarless corneal repair

Sci Adv. 2024 Dec 20;10(51):eadt1643. doi: 10.1126/sciadv.adt1643. Epub 2024 Dec 18.

Abstract

Corneal injury-induced fibrosis occurs because of corneal epithelial basement membrane (EBM) injury and defective regeneration. Corneal fibrosis inhibition and transparency restoration depend on reestablished EBM, where the collagen network provides structural stability and heparan sulfate binds corneal epithelium-derived cytokines to regulate homeostasis. Inspired by this, bioactive hydrogels (Hep@Gel) composed of collagen-derived gelatins and highly anionic heparin were constructed for scarless corneal repair. Hep@Gel resembled the barrier function of the EBM regarding surface-confined binding, long-time sequestration, and progressive degradation of IL-1, TGF-β, and PDGF-BB, which robustly inhibited the apoptosis and myofibroblast transition of keratocytes. Animal models of rabbits and nonhuman primates confirmed that Hep@Gel effectively limited the influx of inflammatory and fibrotic cytokines from the epithelium into the stroma to down-regulate the wound healing cascade, contributing to better vision quality with 73% reduced fibrosis. Hep@Gel offers a solution for preventing corneal injury-induced scarring and substituting for lamellar keratoplasty to remove scarring.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Cicatrix / metabolism
  • Cicatrix / pathology
  • Cornea / drug effects
  • Cornea / metabolism
  • Cornea / pathology
  • Corneal Injuries / drug therapy
  • Corneal Injuries / metabolism
  • Corneal Injuries / pathology
  • Disease Models, Animal
  • Humans
  • Hydrogels* / chemistry
  • Rabbits
  • Wound Healing* / drug effects

Substances

  • Hydrogels
  • Biocompatible Materials