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用于神经组织再生的氧化石墨烯复合水凝胶的3D生物打印

3D Bioprinting of Graphene Oxide-Incorporated Hydrogels for Neural Tissue Regeneration.

作者信息

Lai Jiahui, Chen Xiaodie, Lu Helen H, Wang Min

机构信息

Department of Mechanical Engineering, The University of Hong Kong, Hong Kong, Hong Kong.

Department of Biomedical Engineering, Columbia University, New York, New York, USA.

出版信息

3D Print Addit Manuf. 2024 Dec 16;11(6):e2022-e2032. doi: 10.1089/3dp.2023.0150. eCollection 2024 Dec.

Abstract

Bioprinting has emerged as a powerful manufacturing platform for tissue engineering, enabling the fabrication of 3D living structures by assembling living cells, biological molecules, and biomaterials into these structures. Among various biomaterials, hydrogels have been increasingly used in developing bioinks suitable for 3D bioprinting for diverse human body tissues and organs. In particular, hydrogel blends combining gelatin and gelatin methacryloyl (GelMA; "GG hydrogels") receive significant attention for 3D bioprinting owing to their many advantages, such as excellent biocompatibility, biodegradability, intrinsic bioactive groups, and polymer networks that combine the thermoresponsive gelation feature of gelatin and chemically crosslinkable attribute of GelMA. However, GG hydrogels have poor electroactive properties, which hinder their applications in neural tissue engineering where electrical conductivity is required. To overcome this problem, in this study, a small amount of highly electroactive graphene oxide (GO) was added in GG hydrogels to generate electroactive hydrogels for 3D bioprinting in neural tissue engineering. The incorporation of GO nanoparticles slightly improved mechanical properties and significantly increased electrical conductivity of GG hydrogels. All GO/GG composite hydrogels exhibited shear thinning behavior and sufficient viscosity and hence could be 3D printed into 3D porous scaffolds with good shape fidelity. Furthermore, bioinks combining rat bone marrow-derived mesenchymal stem cells (rBMSCs) with GO/GG composite hydrogels could be 3D bioprinted into GO/GG constructs with high cell viability. GO nanoparticles in the constructs provided ultraviolet (UV) shading effect and facilitated cell survival during UV exposure after bioprinting. The GO/GG composite hydrogels appear promising for 3D bioprinting applications in repairing damaged neural tissues.

摘要

生物打印已成为组织工程领域强大的制造平台,通过将活细胞、生物分子和生物材料组装到三维结构中,实现了三维活体结构的制造。在各种生物材料中,水凝胶越来越多地用于开发适用于多种人体组织和器官三维生物打印的生物墨水。特别是,结合了明胶和甲基丙烯酰化明胶(GelMA;“GG水凝胶”)的水凝胶混合物因其诸多优点而在三维生物打印中受到广泛关注,这些优点包括优异的生物相容性、可生物降解性、内在生物活性基团以及结合了明胶的热响应凝胶化特性和GelMA的化学可交联属性的聚合物网络。然而,GG水凝胶的电活性较差,这阻碍了它们在需要电导率的神经组织工程中的应用。为了克服这一问题,在本研究中,向GG水凝胶中添加了少量高电活性的氧化石墨烯(GO),以制备用于神经组织工程三维生物打印的电活性水凝胶。GO纳米颗粒的加入略微改善了GG水凝胶的机械性能,并显著提高了其电导率。所有GO/GG复合水凝胶均表现出剪切变稀行为和足够的粘度,因此可以三维打印成具有良好形状保真度的三维多孔支架。此外,将大鼠骨髓间充质干细胞(rBMSCs)与GO/GG复合水凝胶相结合的生物墨水可以三维生物打印成具有高细胞活力的GO/GG构建体。构建体中的GO纳米颗粒提供了紫外线(UV)遮蔽效果,并有助于生物打印后紫外线照射期间细胞的存活。GO/GG复合水凝胶在修复受损神经组织的三维生物打印应用中似乎很有前景。

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