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用于无缝合修复深层前角膜缺损的复制人眼角膜基质结构的水凝胶补片。

Corneal stromal structure replicating humanized hydrogel patch for sutureless repair of deep anterior-corneal defect.

机构信息

Eye Institute of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Qingdao, 266071, China.

Eye Institute of Shandong First Medical University, Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), Jinan, 250021, China.

出版信息

Biomaterials. 2025 Feb;313:122754. doi: 10.1016/j.biomaterials.2024.122754. Epub 2024 Aug 14.

DOI:10.1016/j.biomaterials.2024.122754
PMID:39197237
Abstract

A critical shortage of donor corneas exists worldwide. Hydrogel patches with a biological architecture and functions that simulate those of native corneas have garnered considerable attention. This study introduces a stromal structure replicating corneal patch (SRCP) composed of a decellularized cornea-templated nanotubular skeleton, recombinant human collagen, and methacrylated gelatin, exhibiting a similar ultrastructure and transmittance (above 80 %) to natural cornea. The SRCP is superior to the conventional recombinant human collagen patch in terms of biomechanical properties and resistance to enzymatic degradation. Additionally, SRCP promotes corneal epithelial and stromal cell migration while preventing the trans-differentiation of stromal cells into myofibroblasts. When applied to an ocular surface (37 °C), SRCP releases methacrylated gelatin, which robustly binds SRCP to the corneal stroma after activation by 405 nm light. Compared to gelatin-based photocurable hydrogel, the SRCP better supports the restoration of normal corneal curvature and withstands deformation under an elevated intraocular pressure (100 mmHg). In an in vivo deep anterior-corneal defect model, SRCP facilitated epithelial healing and vision recovery within 2 weeks, maintained graft structural stability, and inhibited stromal scarring at 4 weeks post-operation. The ideal performance of the SRCP makes it a promising humanized corneal equivalent for sutureless clinical applications.

摘要

全世界都存在供体角膜严重短缺的问题。具有模拟天然角膜生物结构和功能的水凝胶贴片引起了广泛关注。本研究介绍了一种由脱细胞角膜模板纳米管状骨架、重组人胶原蛋白和甲基丙烯酰化明胶组成的基质结构复制角膜贴片(SRCP),其具有类似于天然角膜的超微结构和透光率(超过 80%)。与传统的重组人胶原蛋白贴片相比,SRCP 在生物力学性能和抗酶降解方面具有优势。此外,SRCP 促进角膜上皮和基质细胞迁移,同时防止基质细胞向肌成纤维细胞的转分化。当应用于眼表面(37°C)时,SRCP 释放甲基丙烯酰化明胶,在 405nm 光激活后,甲基丙烯酰化明胶可使 SRCP 牢固地结合到角膜基质上。与基于明胶的光固化水凝胶相比,SRCP 更有利于恢复正常的角膜曲率,并在 100mmHg 的高眼压下耐受变形。在体内深层前角膜缺损模型中,SRCP 可在 2 周内促进上皮愈合和视力恢复,在术后 4 周时保持移植物结构稳定,并抑制基质瘢痕形成。SRCP 的理想性能使其成为一种有前途的、适合于无缝线临床应用的人源化角膜等效物。

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