用于三维打印的组织特异性水凝胶及其在外周神经再生中的潜在应用。

Tissue-Specific Hydrogels for Three-Dimensional Printing and Potential Application in Peripheral Nerve Regeneration.

机构信息

Guangdong Peripheral Nerve Tissue Engineering and Technology Research Center, Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Guangdong Provincial Soft Tissue Biofabrication Engineering Laboratory, Guangzhou, China.

出版信息

Tissue Eng Part A. 2022 Feb;28(3-4):161-174. doi: 10.1089/ten.TEA.2021.0093. Epub 2022 Jan 5.

Abstract

Decellularized extracellular matrix hydrogel (dECM-G) has demonstrated its significant tissue-specificity, high biocompatibility, and versatile utilities in tissue engineering. However, the low mechanical stability and fast degradation are major drawbacks for its application in three-dimensional (3D) printing. Herein, we report a hybrid hydrogel system consisting of dECM-Gs and photocrosslinkable gelatin methacrylate (GelMA), which resulted in significantly improved printability and structural fidelity. These premixed hydrogels retained high bioactivity and tissue-specificity due to their containing dECM-Gs. More specifically, it was realized that the hydrogel containing dECM-G derived from porcine peripheral nerves (GelMA/pDNM-G) effectively facilitated neurite growth and Schwann cell migration from two-dimensional cultured dorsal root ganglion explants. The nerve cells were also encapsulated in the GelMA/pDNM-G hydrogel for 3D culture or underwent cell-laden bioprinting with high cell viability. The preparation of such GelMA/dECM-G hydrogels enabled the recapitulation of functional tissues through extrusion-based bioprinting, which holds great potential for applications in regenerative medicine. Impact statement Tissue-derived decellularized matrices have drawn broad interests for their versatile applications in tissue engineering and regenerative medicine, especially the decellularized peripheral nerve matrix, which can effectively facilitate axonal extension, remyelination, and neural functional restoration after peripheral nerve injury. However, neither decellularized porcine nerve matrix (pDNM) nor pDNM hydrogel (pDNM-G) can be directly used in three-dimensional printing for personalized nerve constructs or cell transplantation. This work developed a hybrid hydrogel consisting of decellularized extracellular matrix hydrogel (dECM-G) and photocrosslinkable gelatin methacrylate (GelMA), which resulted in significantly improved printability and structural fidelity. The GelMA/pDNM-G hydrogel retained high bioactivity and tissue-specificity due to its dECM-G content. Such hybrid hydrogel systems built up a springboard in advanced biomaterials for neural tissue engineering, as well as a promising strategy for dECM containing bioprinting.

摘要

去细胞细胞外基质水凝胶(dECM-G)在组织工程中表现出显著的组织特异性、高生物相容性和多功能性。然而,其机械稳定性低和快速降解是其在三维(3D)打印中应用的主要缺点。本文报道了一种由去细胞细胞外基质水凝胶(dECM-G)和光交联明胶甲基丙烯酰胺(GelMA)组成的混合水凝胶系统,该系统显著提高了可打印性和结构保真度。由于含有 dECM-G,这些预混合水凝胶保持了高生物活性和组织特异性。更具体地说,我们意识到含有源自猪周围神经的 dECM-G 的水凝胶(GelMA/pDNM-G)有效地促进了二维培养的背根神经节外植体的轴突生长和施万细胞迁移。神经细胞也被包裹在 GelMA/pDNM-G 水凝胶中进行 3D 培养,或通过高细胞活力进行细胞负载生物打印。GelMA/dECM-G 水凝胶的制备能够通过基于挤出的生物打印来再现功能性组织,这为再生医学中的应用提供了巨大的潜力。 组织来源的去细胞化细胞外基质因其在组织工程和再生医学中的广泛应用而受到广泛关注,特别是去细胞化周围神经基质,它可以有效地促进轴突延伸、髓鞘形成和周围神经损伤后的神经功能恢复。然而,去细胞化的猪神经基质(pDNM)或 pDNM 水凝胶(pDNM-G)都不能直接用于三维打印用于个性化神经构建或细胞移植。这项工作开发了一种由去细胞细胞外基质水凝胶(dECM-G)和光交联明胶甲基丙烯酰胺(GelMA)组成的混合水凝胶,显著提高了可打印性和结构保真度。由于含有 dECM-G,GelMA/pDNM-G 水凝胶保留了高生物活性和组织特异性。这种混合水凝胶系统为神经组织工程中的先进生物材料搭建了一个跳板,也为含 dECM 的生物打印提供了一个有前途的策略。

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