Chen Fang, Han Uiyoung, Wungcharoen Thitima, Seo Youngyoon Amy, Le Peter, Jiang Li, Kang Nae-Won, Song Euisun, Jang Kyeongwoo, Mundy David, Fernandes-Cunha Gabriella Maria, Heilshorn Sarah, Myung David
Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA.
VA Palo Alto Health Care System, Palo Alto, CA, USA.
NPJ Regen Med. 2025 Feb 4;10(1):8. doi: 10.1038/s41536-024-00385-9.
Corneal transplantation is the primary treatment for corneal blindness, affecting millions globally. However, challenges like donor scarcity and surgical complications remain. Recently, in situ-forming corneal stroma substitutes have emerged, offering potential solutions to these limitations. These substitutes enable liquid-to-hydrogel formation in situ, eliminating sutures and reducing complications. Here we performed a direct, side-by-side comparison of a composite hyaluronan-collagen (HA-Col) hydrogel crosslinked by either photochemistry or bio-orthogonal chemistry to ascertain the impact of reaction specificity on corneal wound healing. Testing in rodent and rabbit models suggests that composite HA-Col gels crosslinked by bio-orthogonal chemistry results in more rapid and optically favorable wound healing compared to the same composition crosslinked by photochemistry as well as bio-orthogonally crosslinked collagen alone. These findings underscore biochemical parameters that may be important to the success of crosslinked, in situ-forming hydrogels as an alternative to corneal transplantation, with the potential for expanded access to treatment and improved outcomes.
角膜移植是治疗角膜盲的主要方法，全球有数百万人受其影响。然而，供体稀缺和手术并发症等挑战依然存在。最近，原位形成的角膜基质替代物出现了，为这些局限性提供了潜在的解决方案。这些替代物能够在原位实现液体到水凝胶的形成，无需缝合线并减少并发症。在此，我们对通过光化学或生物正交化学交联的复合透明质酸 - 胶原蛋白（HA - Col）水凝胶进行了直接的并排比较，以确定反应特异性对角膜伤口愈合的影响。在啮齿动物和兔子模型中的测试表明，与通过光化学交联的相同成分以及单独的生物正交交联胶原蛋白相比，通过生物正交化学交联的复合HA - Col凝胶能实现更快且光学效果更好的伤口愈合。这些发现强调了生化参数，这些参数对于交联的原位形成水凝胶作为角膜移植替代物的成功可能很重要，具有扩大治疗可及性和改善治疗效果的潜力。
