3D bioprinted GelMA/collagen hydrogel for corneal stroma regeneration.

IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Yingni Xu, Wenfang Liu, Qi Zhao, Xiaoyan Feng, Zhibiao Li, Yongrui Huang, Jia Liu, Yuehai Peng, Wenjing Song, Li Ren
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Abstract

Blindness caused by corneal stroma disease affects millions worldwide, the regeneration of corneal stroma has always been a challenge due to its sophisticated curvature structure and keratocyte-fibroblast transformation. In this study, we developed and optimized a series of gelatin methacrylate (GelMA)/collagen-based bioinks to fabricate convex corneal implants via 3D printing techniques. A novel method was proposed to enhance collagen solubility in neutral solutions by combining 2,3-epoxypropyltrimethylammonium chloride (EPTAC) with high-molecular-weight type I collagen, with simulations suggesting that the mechanism primarily involved electrostatic interactions. To evaluate whether keratocytes respond to a convex microenvironment and to verify the effectiveness of the proposed printing strategy for corneal stromal regeneration, particularly in mitigating corneal fibrosis, we fabricated topological structures of both flat and convex corneas. These structures were systematically analyzed for their influence on keratocyte-to-fibroblast transformation and keratocyte phenotype maintenance. Morphological observations, along with gene and protein expression analyses, demonstrated that the convex architecture provided an optimal microenvironment for preserving the keratocyte phenotype. Moreover, in vivo transplantation revealed the convex cornea effectively suppressed corneal fibrosis compared to the flat cornea. These findings suggest that convex cornea holds promise as a potential translational approach for treating corneal stroma regeneration.

3D生物打印凝胶/胶原水凝胶用于角膜基质再生。
角膜基质疾病导致的失明影响着全球数百万人,由于其复杂的曲率结构和角化细胞-成纤维细胞转化,角膜基质的再生一直是一个挑战。在这项研究中,我们开发并优化了一系列基于甲基丙烯酸明胶(GelMA)/胶原蛋白的生物墨水,通过3D打印技术制造凸面角膜植入物。提出了一种新的方法,通过将2,3-环氧丙基三甲基氯化铵(EPTAC)与高分子量I型胶原结合来提高胶原在中性溶液中的溶解度,模拟表明其机制主要涉及静电相互作用。为了评估角膜细胞是否对凸微环境有反应,并验证所提出的角膜基质再生打印策略的有效性,特别是在减轻角膜纤维化方面,我们制造了平面和凸角膜的拓扑结构。系统地分析了这些结构对角化细胞向成纤维细胞转化和角化细胞表型维持的影响。形态学观察以及基因和蛋白表达分析表明,凸结构为保存角化细胞表型提供了最佳的微环境。此外,体内移植显示,与平角膜相比,凸角膜能有效抑制角膜纤维化。这些发现表明,凸面角膜有望成为治疗角膜基质再生的潜在转化方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biofabrication
Biofabrication ENGINEERING, BIOMEDICAL-MATERIALS SCIENCE, BIOMATERIALS
CiteScore
17.40
自引率
3.30%
发文量
118
审稿时长
2 months
期刊介绍: Biofabrication is dedicated to advancing cutting-edge research on the utilization of cells, proteins, biological materials, and biomaterials as fundamental components for the construction of biological systems and/or therapeutic products. Additionally, it proudly serves as the official journal of the International Society for Biofabrication (ISBF).
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