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Abstract
Neural regeneration is extremely difficult to achieve. In traumatic brain injuries, the loss of brain parenchyma volume hinders neural regeneration. In this study, neuronal tissue engineering was performed by using electrically charged hydrogels composed of cationic and anionic monomers in a 1:1 ratio (C1A1 hydrogel), which served as an effective scaffold for the attachment of neural stem cells (NSCs). In the 3D environment of porous C1A1 hydrogels engineered by the cryogelation technique, NSCs differentiated into neuroglial cells. The C1A1 porous hydrogel was implanted into brain defects in a mouse traumatic damage model. The VEGF-immersed C1A1 porous hydrogel promoted host-derived vascular network formation together with the infiltration of macrophages/microglia and astrocytes into the gel. Furthermore, the stepwise transplantation of GFP-labeled NSCs supported differentiation towards glial and neuronal cells. Therefore, this two-step method for neural regeneration may become a new approach for therapeutic brain tissue reconstruction after brain damage in the future.
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1 Hokkaido University, Department of Cancer Pathology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691)
2 Hokkaido University, Department of Cancer Pathology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691)
3 Hokkaido University, Faculty of Advanced Life Science, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691)
4 Hokkaido University, Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691)
5 Hokkaido University, Research Institute for Electronic Science, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); National Institutes of Natural Sciences, Biophotonics Research Group, Exploratory Research Center on Life and Living Systems (ExCELLS) and National Institute for Physiological Sciences, Okazaki, Japan (GRID:grid.250358.9) (ISNI:0000 0000 9137 6732)
6 Hokkaido University, Graduate School of Life Science, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691)
7 Hokkaido University, Department of Cancer Pathology, Faculty of Medicine, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Research Institute for Electronic Science, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691)
8 Hokkaido University, Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Hokkaido University, Faculty of Advanced Life Science, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691)