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.

中文翻译：

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用于无疤痕角膜修复的生物启发生物活性水凝胶


角膜损伤诱导的纤维化是由于角膜上皮基底膜 （EBM） 损伤和再生缺陷而发生的。角膜纤维化抑制和透明度恢复取决于重建的 EBM，其中胶原蛋白网络提供结构稳定性，硫酸乙酰肝素结合角膜上皮衍生的细胞因子以调节体内平衡。受此启发，构建了由胶原蛋白衍生的明胶和高阴离子肝素组成的生物活性水凝胶 （Hep@Gel） 用于无疤痕角膜修复。Hep@Gel类似于 EBM 在 IL-1 、 TGF-β 和 PDGF-BB 的表面限制结合、长期隔离和进行性降解方面的屏障功能，从而强烈抑制角质细胞的细胞凋亡和肌成纤维细胞转化。兔子和非人灵长类动物的动物模型证实，Hep@Gel 有效地限制了炎症和纤维化细胞因子从上皮流入基质，以下调伤口愈合级联反应，有助于提高视力质量，纤维化减少了 73%。Hep@Gel 提供了一种预防角膜损伤引起的疤痕并替代板层角膜移植术以去除疤痕的解决方案。