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脱细胞基质生物墨水与甲基丙烯酸明胶结合,可同时改善打印性能和生物功能。

Decellularized matrix bioink with gelatin methacrylate for simultaneous improvements in printability and biofunctionality.

机构信息

Nano-Convergence Manufacturing Systems Research Division, Korea Institute of Machinery and Materials, Daejeon 34103, Republic of Korea; Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.

Medical Research Institute, Pusan National University, Yangsan 50612, Republic of Korea.

出版信息

Int J Biol Macromol. 2024 Mar;262(Pt 2):130194. doi: 10.1016/j.ijbiomac.2024.130194. Epub 2024 Feb 14.

Abstract

Gelatin methacrylate (GelMA) bioink has been widely used in bioprinting because it is a printable and biocompatible biomaterial. However, it is difficult to print GelMA bioink without any temperature control because it has a thermally-sensitive rheological property. Therefore, in this study, we developed a temperature-controlled printing system in real time without affecting the viability of the cells encapsulated in the bioink. In addition, a skin-derived decellularized extracellular matrix (SdECM) was printed with GelMA to better mimic the native tissue environment compared with solely using GelMA bioink with the enhancement of structural stability. The temperature setting accuracy was calculated to be 98.58 ± 1.8 % for the module and 99.48 ± 1.33 % for the plate from 5 °C to 37 °C. The group of the temperature of the module at 10 °C and the plate at 20 °C have 93.84 % cell viability with the printable range in the printability window. In particular, the cell viability and proliferation were increased in the encapsulated fibroblasts in the GelMA/SdECM bioink, relative to the GelMA bioink, with a morphology that significantly spread for seven days. The gene expression and growth factors related to skin tissue regeneration were relatively upregulated with SdECM components. In the bioprinting process, the rheological properties of the GelMA/SdECM bioink were successfully adjusted in real time to increase printability, and the native skin tissue mimicked components providing tissue-specific biofunctions to the encapsulated cells. The developed bioprinting strategies and bioinks could support future studies related to the skin tissue reconstruction, regeneration, and other medical applications using the bioprinting process.

摘要

明胶甲基丙烯酰(GelMA)生物墨水由于其具有可打印性和生物相容性,已被广泛应用于生物打印领域。然而,由于其具有热敏流变特性,在没有任何温度控制的情况下很难打印 GelMA 生物墨水。因此,在本研究中,我们开发了一种实时温度控制打印系统,在不影响生物墨水中包裹细胞活力的情况下进行打印。此外,与仅使用 GelMA 生物墨水相比,使用 GelMA 打印皮肤衍生的去细胞细胞外基质(SdECM)可以更好地模拟天然组织环境,同时增强结构稳定性。从 5°C 到 37°C,模块的温度设置精度计算为 98.58±1.8%,而板的温度设置精度为 99.48±1.33%。模块温度为 10°C 和板温度为 20°C 的组的细胞活力为 93.84%,打印范围在可打印窗口内。特别是,与 GelMA 生物墨水相比,GelMA/SdECM 生物墨水中包裹的成纤维细胞的细胞活力和增殖增加,其形态在七天内显著扩散。与 SdECM 成分相关的皮肤组织再生的基因表达和生长因子相对上调。在生物打印过程中,GelMA/SdECM 生物墨水的流变特性可实时成功调整,以提高可打印性,并且模拟天然皮肤组织的成分向包裹的细胞提供组织特异性的生物功能。所开发的生物打印策略和生物墨水可以支持未来与皮肤组织重建、再生和其他生物打印过程相关的医学应用研究。

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