Koivisto Janne T, Joki Tiina, Parraga Jenny E, Pääkkönen Rami, Ylä-Outinen Laura, Salonen Laura, Jönkkäri Ilari, Peltola Marja, Ihalainen Teemu O, Narkilahti Susanna, Kellomäki Minna
BioMediTech Institute and Faculty of Biomedical Sciences and Engineering, Tampere University of Technology, Korkeakoulunkatu 3, FI-33720 Tampere, Finland. BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Lääkärinkatu 1, FI-33520 Tampere, Finland.
Biomed Mater. 2017 Mar 24;12(2):025014. doi: 10.1088/1748-605X/aa62b0.
Neural tissue engineering and three-dimensional in vitro tissue modeling require the development of biomaterials that take into account the specified requirements of human neural cells and tissue. In this study, an alternative method of producing biomimetic hydrogels based on gellan gum (GG) was developed by replacing traditional crosslinking methods with the bioamines spermidine and spermine. These bioamines were proven to function as crosslinkers for GG hydrogel at +37 °C, allowing for the encapsulation of human neurons. We studied the mechanical and rheological properties of the formed hydrogels, which showed biomimicking properties comparable to naïve rabbit brain tissue under physiologically relevant stress and strain. Human pluripotent stem cell-derived neuronal cells demonstrated good cytocompatibility in the GG-based hydrogels. Moreover, functionalization of GG hydrogels with laminin resulted in cell type-specific behavior: neuronal cell maturation and neurite migration.
神经组织工程和三维体外组织建模需要开发考虑人类神经细胞和组织特定要求的生物材料。在本研究中,通过用生物胺亚精胺和精胺替代传统交联方法,开发了一种基于结冷胶(GG)生产仿生水凝胶的替代方法。这些生物胺被证明在37°C时可作为GG水凝胶的交联剂,能够封装人类神经元。我们研究了形成的水凝胶的力学和流变学特性,结果表明,在生理相关的应力和应变下,其具有与未处理的兔脑组织相当的仿生特性。人多能干细胞衍生的神经元细胞在基于GG的水凝胶中表现出良好的细胞相容性。此外,用层粘连蛋白对GG水凝胶进行功能化处理会导致细胞类型特异性行为:神经元细胞成熟和神经突迁移。