Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds  

作　　者：Chia-Chen Hsu Julian H.George Sharlayne Waller Cyril Besnard David A Nagel Eric J Hill Michael D.Coleman Alexander M.Korsunsky Zhanfeng Cui Hua Ye 

机构地区：[1]Institute of Biomedical Engineering,Department of Engineering Science,University of Oxford,OX37DQ,UK [2]MBLEM,Department of Engineering Science,University of Oxford,Parks Road,Oxford,OX13PJ,UK [3]School of Biosciences,College of Health and Life Sciences,Aston University,Birmingham,B47ET,UK [4]Translational Medicine Research Group,Aston Medical School,College of Health and Life Sciences,Aston University,Birmingham,B47ET,UK

出　　处：《Bioactive Materials》2022年第3期358-372,共15页生物活性材料（英文）

基　　金：This study was supported by funding from the Biotechnology and Biological Sciences Research Council(BB/H008527/1)(www.bbsrc.ac.uk);China Regenerative Medicine International(CRMI),Jiangsu Industrial Technology Research Institute(JITRI),and Engineering and Physical Sciences Research Council(EPSRC EP/P005381/1 and EP/V007785/1).

摘　　要：To reflect human development,it is critical to create a substrate that can support long-term cell survival,differentiation,and maturation.Hydrogels are promising materials for 3D cultures.However,a bulk structure consisting of dense polymer networks often leads to suboptimal microenvironments that impedes nutrient exchange and cell-to-cell interaction.Herein,granular hydrogel-based scaffolds were used to support 3D human induced pluripotent stem cell(hiPSC)-derived neural networks.A custom designed 3D printed toolset was developed to extrude hyaluronic acid hydrogel through a porous nylon fabric to generate hydrogel granules.Cells and hydrogel granules were combined using a weaker secondary gelation step,forming self-supporting cell laden scaffolds.At three and seven days,granular scaffolds supported higher cell viability compared to bulk hydrogels,whereas granular scaffolds supported more neurite bearing cells and longer neurite extensions(65.52±11.59μm)after seven days compared to bulk hydrogels(22.90±4.70μm).Long-term(three-month)cultures of clinically relevant hiPSC-derived neural cells in granular hydrogels supported well established neuronal and astrocytic colonies and a high level of neurite extension both inside and beyond the scaffold.This approach is significant as it provides a simple,rapid and efficient way to achieve a tissue-relevant granular structure within hydrogel cultures.

关 键 词：MICROGEL HYDROGEL HYALURONAN IPSC Neural tissue engineering 3D printing 

分 类 号：TB332[一般工业技术—材料科学与工程]