{"title":"3D bioprinted GelMA/collagen hydrogel for corneal stroma regeneration.","authors":"Yingni Xu, Wenfang Liu, Qi Zhao, Xiaoyan Feng, Zhibiao Li, Yongrui Huang, Jia Liu, Yuehai Peng, Wenjing Song, Li Ren","doi":"10.1088/1758-5090/ade7b2","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2000,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biofabrication","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1088/1758-5090/ade7b2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
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.
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).