Liao Yi, Zhou Shengmei, Quantock Andrew J, Li Wei, Xu Yuan, Fang Xie, Young Robert D, He Wanling, Li Qingjian, Zhang Houjian, Wang Ruochen, Han Yi, Cheng Hongwei, Li Wenjun, Peng Lu, Zong Rongrong, Hong Yi, Lin Zhirong, Liu Zuguo
Xiamen University Affiliated Xiamen Eye Center, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Fujian Engineering and Research Center of Eye Regenerative Medicine, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, China.
School of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales, United Kingdom.
Mater Today Bio. 2025 Jul 17;34:102110. doi: 10.1016/j.mtbio.2025.102110. eCollection 2025 Oct.
Although cell-encapsulating hydrogels are of tremendous interest in regenerative medicine, few of them have been used in clinics and rarely used natural extracellular matrices as polymer precursors. One successful example is to use riboflavin (RF)/ultraviolet A (UVA) to cross-link corneal collagen, which has been used in clinics to halt disease progression in patients with corneal ectatic diseases. However, high-energy UVA and its action on RF cause tissue damage, particularly irreversible endothelium loss, and thus standard RF/UVA protocol may have limitations in treating patients at the advanced stage with thin cornea. Photo-initiators lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) has high efficiency under visible 405 nm light, and is widely applied in 3D bioprinting to cross-link synthesized monomers. Here, we introduced a new strategy to cross-link cornea using LAP and visible light (VL). The LAP/VL protocol could effectively increase corneal stiffness with equivalent efficiency to the RF/UVA protocol in both porcine and rabbit cornea. As LAP and VL were used, the loss of corneal endothelial and stromal cells was minimized, and epithelial wound healing and stromal cell repopulation were accelerated. In summary, we propose that the LAP/VL protocol is an effective and safe alternate for cornea CXL with advantages for relatively thin cornea. Our study also expands the application scope of LAP, indicating it is a suitable photocatalyst for natural extracellular matrices CXL.
尽管细胞包封水凝胶在再生医学中备受关注，但其中很少有被用于临床的，并且很少使用天然细胞外基质作为聚合物前体。一个成功的例子是使用核黄素（RF）/紫外线A（UVA）交联角膜胶原蛋白，这已在临床上用于阻止角膜扩张性疾病患者的疾病进展。然而，高能UVA及其对RF的作用会导致组织损伤，尤其是不可逆的内皮细胞损失，因此标准的RF/UVA方案在治疗晚期薄角膜患者时可能存在局限性。光引发剂苯基-2,4,6-三甲基苯甲酰基膦酸锂（LAP）在405nm可见光下具有高效率，并广泛应用于3D生物打印以交联合成单体。在此，我们介绍了一种使用LAP和可见光（VL）交联角膜的新策略。在猪和兔角膜中，LAP/VL方案能够以与RF/UVA方案相当的效率有效增加角膜硬度。由于使用了LAP和VL，角膜内皮细胞和基质细胞的损失最小化，并且上皮伤口愈合和基质细胞重新填充得到加速。总之，我们提出LAP/VL方案是角膜交联的一种有效且安全的替代方法，对于相对薄的角膜具有优势。我们的研究还扩展了LAP的应用范围，表明它是天然细胞外基质交联的合适光催化剂。
