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使用甲基丙烯酰化明胶和氧化羧甲基纤维素互穿网络水凝胶进行数字光处理3D生物打印仿生角膜基质等效物

Digital light processing 3D bioprinting of biomimetic corneal stroma equivalent using gelatin methacryloyl and oxidized carboxymethylcellulose interpenetrating network hydrogel.

作者信息

Chand Rashik, Janarthanan Gopinathan, Elkhoury Kamil, Vijayavenkataraman Sanjairaj

机构信息

The Vijay Lab, Division of Engineering, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.

Department of Biomedical Engineering, Tandon School of Engineering, New York University, Brooklyn, NY, United States of America.

出版信息

Biofabrication. 2025 Feb 10;17(2). doi: 10.1088/1758-5090/adab27.

Abstract

Corneal blindness, a leading cause of visual impairment globally, has created a pressing need for alternatives to corneal transplantation due to the severe shortage of donor tissues. In this study, we present a novel interpenetrating network hydrogel composed of gelatin methacryloyl (GelMA) and oxidized carboxymethyl cellulose (OxiCMC) for bioprinting a biomimetic corneal stroma equivalent. We tested different combinations of GelMA and OxiCMC to optimize printability and subsequently evaluated these combinations using rheological studies for gelation and other physical, chemical, and biological properties. Using digital light processing (DLP) bioprinting, with tartrazine as a photoabsorber, we successfully biofabricated three-dimensional constructs with improved shape fidelity, high resolution, and excellent reproducibility. The bioprinted constructs mimic the native corneal stroma's curvature, with central and peripheral thicknesses of 478.9 ± 56.5m and 864.0 ± 79.3m, respectively. The dual crosslinking strategy, which combines Schiff base reaction and photocrosslinking, showed an improved compressive modulus (106.3 ± 7.7 kPa) that closely matched that of native tissues (115.3 ± 13.6 kPa), without relying on synthetic polymers, toxic crosslinkers, or nanoparticles. Importantly, the optical transparency of tartrazine-containing corneal constructs was comparable to the native cornea following phosphate-buffered saline washing. Morphological analyses using scanning electron microscopy confirmed the improved porosity, interconnected network, and structural integrity of the GelMA-OxiCMC hydrogel, facilitating better nutrient diffusion and cell viability.biological assays demonstrated high cell viability (>93%) and desirable proliferation of human corneal keratocytes within the biofabricated constructs. Our findings indicate that the GelMA-OxiCMC hydrogel system for DLP bioprinting presents a promising alternative for corneal tissue engineering, offering a potential solution to the donor cornea shortage and advancing regenerative medicine for corneal repair.

摘要

角膜盲是全球视力损害的主要原因,由于供体组织严重短缺,迫切需要角膜移植的替代方法。在本研究中,我们提出了一种由甲基丙烯酰化明胶(GelMA)和氧化羧甲基纤维素(OxiCMC)组成的新型互穿网络水凝胶,用于生物打印仿生角膜基质等效物。我们测试了GelMA和OxiCMC的不同组合以优化可打印性,随后使用流变学研究对这些组合的凝胶化以及其他物理、化学和生物学特性进行评估。使用数字光处理(DLP)生物打印技术,以酒石黄作为光吸收剂,我们成功地生物制造出了具有改善的形状保真度、高分辨率和出色再现性的三维结构。生物打印的结构模仿了天然角膜基质的曲率,中央和周边厚度分别为478.9±56.5μm和864.0±79.3μm。结合席夫碱反应和光交联的双重交联策略显示出改善的压缩模量(106.3±7.7 kPa),与天然组织的压缩模量(115.3±13.6 kPa)非常匹配,且不依赖于合成聚合物、有毒交联剂或纳米颗粒。重要的是,含酒石黄的角膜结构在磷酸盐缓冲盐水洗涤后,其光学透明度与天然角膜相当。使用扫描电子显微镜进行的形态学分析证实了GelMA - OxiCMC水凝胶的孔隙率增加、网络相互连接以及结构完整性改善,有利于更好的营养物质扩散和细胞活力。生物学检测表明,在生物制造的结构中,人角膜角质形成细胞具有高细胞活力(>93%)和理想的增殖能力。我们的研究结果表明,用于DLP生物打印的GelMA - OxiCMC水凝胶系统为角膜组织工程提供了一种有前景的替代方法,为供体角膜短缺问题提供了潜在解决方案,并推动了角膜修复的再生医学发展。

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