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3D 生物打印光交联 GelMA/甲基纤维素水凝胶模拟天然角膜模型,具有增强的体外细胞相容性和持续的角膜基质细胞表型,用于基质再生。

3D bioprinted photo crosslinkable GelMA/methylcellulose hydrogel mimicking native corneal model with enhanced in vitro cytocompatibility and sustained keratocyte phenotype for stromal regeneration.

机构信息

Electrochemical Process Engineering, CSIR-Central Electrochemical Research Institute (CECRI), Karaikudi 630003, Tamil Nadu, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

Electrochemical Process Engineering, CSIR-Central Electrochemical Research Institute (CECRI), Karaikudi 630003, Tamil Nadu, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

出版信息

Int J Biol Macromol. 2024 Apr;264(Pt 1):130472. doi: 10.1016/j.ijbiomac.2024.130472. Epub 2024 Feb 28.

Abstract

Corneal transplantation serves as the standard clinical therapy for serious corneal disorders. However, rejection of grafts, significant expenditures, and most crucially, the global donor shortage, may affect the outcome. Recently, 3D bioprinting using biodegradable polymeric materials has become a suitable method for creating tissue replicas with identical architecture. One such most renowned material is GelMA, for its scaffold's three-dimensional structure, biocompatibility, robust mechanics, and favourable optical transmittance. However, GelMA's inadequate viscosity to print at body temperature with better form integrity remains an obstacle. The aim of this work is to create 3D printed GelMA/MC hydrogels for corneal stroma tissue engineering using MC's printability at room temperature and GelMA's irreversible photo cross-linking with UV irradiation. The print speed and pressure conditions for 3D GelMA/MC hydrogels were tuned. Thermal, morphological and physicochemical characteristics were studied for two distinct concentrations of GelMA/MC hydrogels. The hydrogels achieved a transparency of ~78 % (at 700 nm), which was on par with that of the normal cornea (80 %). The in vitro studies conducted using goat corneal stromal cells demonstrated the ability of both hydrogels to promote cell adhesion and proliferation. Expression of Vimentin and keratan sulphate validated the phenotype of keratocytes in the hydrogel. This 3D printed GelMA/MC hydrogel model mimics biophysical characteristics of the native corneal stroma, which may hold promise for clinical corneal stromal tissue engineering.

摘要

角膜移植是治疗严重角膜疾病的标准临床疗法。然而,移植物排斥、高昂的费用,以及最关键的全球供体短缺,都可能影响治疗效果。最近,使用可生物降解聚合物材料的 3D 生物打印已成为创建具有相同结构的组织复制品的合适方法。其中一种最著名的材料是 GelMA,因为它的支架具有三维结构、生物相容性、坚固的机械性能和良好的光透过率。然而,GelMA 的粘度不足以在体温下进行打印,并且形态完整性较差,这仍然是一个障碍。本工作旨在使用 MC 在室温下的可打印性和 GelMA 与 UV 照射的不可逆光交联来创建用于角膜基质组织工程的 3D 打印 GelMA/MC 水凝胶。对 3D GelMA/MC 水凝胶的打印速度和压力条件进行了调整。研究了两种不同浓度的 GelMA/MC 水凝胶的热、形态和物理化学特性。水凝胶的透光率达到了约 78%(在 700nm 处),与正常角膜相当(80%)。使用山羊角膜基质细胞进行的体外研究表明,两种水凝胶都能够促进细胞黏附和增殖。波形蛋白和硫酸软骨素的表达验证了水凝胶中角膜基质细胞的表型。这种 3D 打印的 GelMA/MC 水凝胶模型模拟了天然角膜基质的生物物理特性,这可能为临床角膜基质组织工程带来希望。

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