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马来酸酐化胶原蛋白的特性分析及其在基于挤出式 3D 生物打印中的生物墨水应用。

Characterization and application of photocrosslinkable collagen maleate as bioink in extrusion-based 3D bioprinting.

机构信息

Department of Chemical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan.

Program of Green Materials and Precision Devices, School of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan.

出版信息

Biomater Sci. 2024 Sep 25;12(19):5063-5075. doi: 10.1039/d4bm00826j.

Abstract

3D bioprinting, a significant advancement in biofabrication, is renowned for its precision in creating tissue constructs. Collagen, despite being a gold standard biomaterial, faces challenges in bioink formulations due to its unique physicochemical properties. This study introduces a novel, neutral-soluble, photocrosslinkable collagen maleate (ColME) that is ideal for 3D bioprinting. ColME was synthesized by chemically modifying bovine type I collagen with maleic anhydride, achieving a high substitution ratio that shifted the isoelectric point to enhance solubility in physiological pH environments. This modification was confirmed to preserve the collagen's triple-helix structure substantially. Bioprinting parameters for ColME were optimized, focusing on adjustments to the bioink concentration, extrusion pressure, nozzle speed, and temperature. Results demonstrated that lower temperatures and smaller nozzle sizes substantially improved the print quality of grid structures. Additionally, the application of intermittent photo-crosslinking facilitated the development of structurally robust 3D multilayered constructs, enabling the stable fabrication of complex tissues. Cell viability assays showed that encapsulated cells within the ColME matrix maintained high viability after printing. When compared to methacrylated gelatin, ColME exhibited superior mechanical strength, resistance to enzymatic digestion, and overall printability, positioning it as an outstanding bioink for the creation of durable, bioactive 3D tissues.

摘要

3D 生物打印是生物制造领域的一项重大进展,以其在组织构建方面的精确性而闻名。胶原蛋白虽然是一种黄金标准的生物材料,但由于其独特的物理化学性质,在生物墨水配方方面面临挑战。本研究引入了一种新型的、中性可溶性的光交联顺丁烯二酸酰化胶原(ColME),非常适合 3D 生物打印。ColME 通过用马来酸酐化学修饰牛 I 型胶原蛋白合成,实现了高取代比,将等电点转移以增强在生理 pH 环境中的溶解度。这种修饰被证实基本保持了胶原蛋白的三螺旋结构。优化了 ColME 的生物打印参数,重点调整了生物墨水浓度、挤出压力、喷嘴速度和温度。结果表明,较低的温度和较小的喷嘴尺寸显著提高了网格结构的打印质量。此外,间歇光交联的应用促进了结构坚固的 3D 多层构建体的发展,能够稳定地制造复杂组织。细胞活力测定表明,打印后包埋在 ColME 基质中的细胞保持高活力。与甲基丙烯酰化明胶相比,ColME 表现出优异的机械强度、抗酶消化性和整体打印性能,使其成为创建耐用、生物活性 3D 组织的出色生物墨水。

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