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一种基于甲基丙烯酸明胶的水凝胶作为用于3D生物打印和神经元分化的潜在生物墨水。

A Gelatin Methacrylate-Based Hydrogel as a Potential Bioink for 3D Bioprinting and Neuronal Differentiation.

作者信息

Cruz Elisa Marozzi, Machado Lucas Simões, Zamproni Laura Nicoleti, Bim Larissa Valdemarin, Ferreira Paula Scanavez, Pinto Leonardo Alves, Pessan Luiz Antonio, Backes Eduardo Henrique, Porcionatto Marimélia Aparecida

机构信息

Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil.

Department of Materials Engineering, Universidade Federal de São Carlos, São Carlos 13565-905, Brazil.

出版信息

Pharmaceutics. 2023 Feb 13;15(2):627. doi: 10.3390/pharmaceutics15020627.

Abstract

Neuronal loss is the ultimate pathophysiologic event in central nervous system (CNS) diseases and replacing these neurons is one of the most significant challenges in regenerative medicine. Providing a suitable microenvironment for new neuron engraftment, proliferation, and synapse formation is a primary goal for 3D bioprinting. Among the various biomaterials, gelatin methacrylate (GelMA) stands out due to its Arg-Gly-Asp (RGD) domains, which assure its biocompatibility and degradation under physiological conditions. This work aimed to produce different GelMA-based bioink compositions, verify their mechanical and biological properties, and evaluate their ability to support neurogenesis. We evaluated four different GelMA-based bioink compositions; however, when it came to their biological properties, incorporating extracellular matrix components, such as Geltrex, was essential to ensure human neuroprogenitor cell viability. Finally, Geltrex: 8% GelMA (1:1) bioink efficiently maintained human neuroprogenitor cell stemness and supported neuronal differentiation. Interestingly, this bioink composition provides a suitable environment for murine astrocytes to de-differentiate into neural stem cells and give rise to MAP2-positive cells.

摘要

神经元丢失是中枢神经系统(CNS)疾病最终的病理生理事件,而替换这些神经元是再生医学中最重大的挑战之一。为新神经元植入、增殖和突触形成提供合适的微环境是3D生物打印的主要目标。在各种生物材料中,甲基丙烯酸明胶(GelMA)因其具有精氨酸-甘氨酸-天冬氨酸(RGD)结构域而脱颖而出,该结构域确保了其生物相容性以及在生理条件下的降解性。这项工作旨在制备不同的基于GelMA的生物墨水组合物,验证其机械和生物学特性,并评估它们支持神经发生的能力。我们评估了四种不同的基于GelMA的生物墨水组合物;然而,就其生物学特性而言,加入细胞外基质成分(如Geltrex)对于确保人类神经祖细胞的活力至关重要。最后,Geltrex:8%GelMA(1:1)生物墨水有效地维持了人类神经祖细胞的干性并支持神经元分化。有趣的是,这种生物墨水组合物为小鼠星形胶质细胞去分化为神经干细胞并产生微管相关蛋白2(MAP2)阳性细胞提供了合适的环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64a4/9959598/a4ef3d5d05a6/pharmaceutics-15-00627-g001.jpg

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