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基于细胞外基质的生物黏附性水凝胶用于无痕修复深层前角膜缺损。

ECM-based bioadhesive hydrogel for sutureless repair of deep anterior corneal defects.

机构信息

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Research Center for Advanced Technologies in Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran 1411713138, Iran.

出版信息

Biomater Sci. 2024 Apr 30;12(9):2356-2368. doi: 10.1039/d4bm00129j.

Abstract

Corneal transplantation is the gold standard treatment for corneal-related blindness; however, this strategy faces challenges such as limited donor cornea, graft rejection, suture-related complications, and the need for specialized equipment and advanced surgical skills. Development of tissue adhesives for corneal regeneration is of great clinical value. However, currently available corneal tissue sealants pose challenges, such as lack of safety, biocompatibility, and desired mechanical properties. To meet these requirements simultaneously, a bovine stromal corneal extracellular matrix (dCor) was used to design a bioadhesive photocurable hydrogel based on gelatin methacrylate (GelMA) and polyethylene glycol diacrylate (PEGDA) hydrogels (dCor/Gel-PEG). Integration of dCor into the dual networks of GelMA and PEGDA (Gel-PEG) led to a bioadhesive hydrogel for curing corneal defects, which could be crosslinked by Irgacure 2959 within 5 min ultraviolet irradiation. The viability of corneal stromal stem cells (CSSCs) was improved on the dCor/Gel-PEG hydrogel in comparison to the Gel-PEG hydrogel. The gene expression profile supported the keratocyte differentiation of CSSCs seeded on dCor/Gel-PEG increased KERA and ALDH, with inhibited myofibroblast transdifferentiation decreased α-SMA due to the presence of dCor. Interestingly, the dCor/Gel-PEG hydrogel exhibited favorable mechanical performance in terms of elasticity and bioadherence to the host corneal stroma. and examinations proved the feasibility of this hydrogel for the sutureless reconstruction of deep anterior corneal defects with promising histopathological results.

摘要

角膜移植是治疗角膜相关失明的金标准方法;然而,这种策略面临着供体角膜有限、移植物排斥、缝线相关并发症以及对专门设备和先进手术技能的需求等挑战。开发用于角膜再生的组织粘合剂具有重要的临床价值。然而,目前可用的角膜组织密封剂存在一些挑战,例如缺乏安全性、生物相容性和所需的机械性能。为了同时满足这些要求,使用牛基质角膜细胞外基质(dCor)设计了一种基于明胶甲基丙烯酸酯(GelMA)和聚乙二醇二丙烯酸酯(PEGDA)水凝胶的生物粘附光固化水凝胶(dCor/Gel-PEG)。将 dCor 整合到 GelMA 和 PEGDA(Gel-PEG)的双网络中,形成一种用于修复角膜缺损的生物粘附水凝胶,可在 5 分钟内通过 Irgacure 2959 紫外线照射交联。与 Gel-PEG 水凝胶相比,角膜基质干细胞(CSSC)在 dCor/Gel-PEG 水凝胶上的活力得到了提高。基因表达谱支持 CSSC 在 dCor/Gel-PEG 上的角膜细胞分化,增加了 KERA 和 ALDH,由于 dCor 的存在,抑制了肌成纤维细胞的转分化,减少了α-SMA。有趣的是,dCor/Gel-PEG 水凝胶在弹性和对宿主角膜基质的生物粘附方面表现出良好的机械性能。组织学和免疫组织化学检查证明了这种水凝胶用于无缝线重建深层前角膜缺损的可行性,具有有前途的组织病理学结果。

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