School of Materials Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Key Laboratory of Biomedical Engineering of Guangdong Province, Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, P. R. China.
Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, P. R. China.
Adv Sci (Weinh). 2023 Apr;10(11):e2205878. doi: 10.1002/advs.202205878. Epub 2023 Feb 12.
Blindness caused by corneal damage affects millions of people worldwide, and this number continues to rise. However, rapid epithelization and a stable epithelium process are the two biggest challenges for traditional corneal materials. These processes are related to corneal curvature, which is an important factor in determination of the corneal healing process and epithelial behavior during corneal damage. In this study, smooth 3D-printed convex corneal implants based on gelatin methacrylate and collagen are generated. As epithelium distribution and adhesion vary in different regions of the natural cornea, this work separates the surfaces into four regions and studies how cells sense topological cues on curvature. It is found that rabbit corneal epithelial cells (RCECs) seeded on steeper slope gradient surfaces on convex structures result in more aligned cell organization and tighter cell-substrate adhesion, which can also be verified through finite element simulation and signaling pathway analysis. In vivo transplantation of convex implants result in a better fit with adjacent tissue and stronger cell adhesion than flat implants, thereby accelerating corneal epithelialization and promoting collagen fibers and neural regeneration within 180 days. Taken together, printed convex corneal implants that facilitate corneal regeneration may offer a translational strategy for the treatment of corneal damage.
角膜损伤导致的失明影响着全球数百万人，且这一数字还在不断增加。然而，传统角膜材料面临的两大挑战是快速上皮化和稳定的上皮过程。这些过程与角膜曲率有关，角膜曲率是决定角膜愈合过程和损伤时上皮行为的重要因素。本研究基于甲基丙烯酸明胶和胶原蛋白生成了光滑的 3D 打印凸面角膜植入物。由于天然角膜的不同区域上皮细胞的分布和黏附存在差异，本工作将表面分为四个区域，并研究细胞如何感知曲率的拓扑线索。研究发现，在凸面结构上较陡的斜率梯度表面上接种的兔角膜上皮细胞（RCEC）会导致更规则的细胞组织排列和更紧密的细胞-基底黏附，这也可以通过有限元模拟和信号通路分析来验证。凸面植入物的体内移植与相邻组织的贴合度更好，细胞黏附更强，从而加速角膜上皮化，并在 180 天内促进胶原纤维和神经再生。综上所述，有助于角膜再生的 3D 打印凸面角膜植入物可能为治疗角膜损伤提供一种转化策略。
