Xie Lijie, Dong Xiaojuan, Ji Jianping, Ouyang Chen, Wu Jing, Hou Chao, Huang Ting
Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Mater Today Bio. 2024 Feb 22;25:101003. doi: 10.1016/j.mtbio.2024.101003. eCollection 2024 Apr.
Corneal endothelial keratoplasty has been the primary treatment method of endothelial decompensation, but it is often limited in clinical practice due to global shortage of donor cornea. Here, we explored using an ultra-thin allogeneic cornea-derived matrix (uACM) films as a substrate for constructing bioengineered corneal endothelial grafts. We evaluated the films' optical, mechanical, and structural properties, and measured the composition of the extracellular matrix. The uACM was an ultrathin and curved cornea-shaped film with favorable optical and mechanical properties. The fabrication process efficiently preserved corneal extracellular matrix composition and significantly decreased cellular components. Moreover, human corneal endothelial cells and rabbit corneal endothelial cells (RCECs) can adhere and grow on the uACM films with a positive expression of the corneal endothelial functional markers Na/K-ATPase and ZO-1. The successful transplantation of uACM with RCECs grafts into the rabbit model of endothelial dysfunction via Descemet membrane endothelial keratoplasty resulted in prompt restoration of corneal transparency and thickness. During the four-week follow-up period, the uACM with RCECs implanted eyes exhibited comparable corneal transparency, central corneal thickness, and endothelial cell count to that of the healthy rabbit. Histologic examination revealed that the grafts were successfully attached and integrated onto the posterior surface of the corneal stroma. The uACM achieved biomimetic reconstruction in terms of both composition and structure, and can be used to construct the bioengineered corneal endothelial grafts. These results indicate that constructing bioengineered corneal endothelial grafts from discarded human corneal tissues may pave the way for generating high-quality corneal endothelial grafts for transplantation.
角膜内皮移植术一直是内皮失代偿的主要治疗方法，但由于供体角膜全球短缺，在临床实践中常受到限制。在此，我们探索使用超薄同种异体角膜衍生基质（uACM）薄膜作为构建生物工程角膜内皮移植物的基质。我们评估了薄膜的光学、力学和结构特性，并测量了细胞外基质的组成。uACM是一种超薄且呈角膜形状的弯曲薄膜，具有良好的光学和力学性能。制备过程有效地保留了角膜细胞外基质的组成，并显著减少了细胞成分。此外，人角膜内皮细胞和兔角膜内皮细胞（RCECs）可以在uACM薄膜上黏附并生长，角膜内皮功能标志物钠/钾-ATP酶和紧密连接蛋白-1呈阳性表达。通过Descemet膜内皮移植术将uACM与RCECs移植物成功移植到内皮功能障碍的兔模型中，可使角膜透明度和厚度迅速恢复。在四周的随访期内，植入uACM与RCECs的眼睛在角膜透明度、中央角膜厚度和内皮细胞计数方面与健康兔相当。组织学检查显示移植物成功附着并整合到角膜基质后表面。uACM在组成和结构方面实现了仿生重建，可用于构建生物工程角膜内皮移植物。这些结果表明，利用废弃的人角膜组织构建生物工程角膜内皮移植物可能为生成高质量的角膜内皮移植移植物铺平道路。
