PMID- 33289773 OWN - NLM STAT- MEDLINE DCOM- 20210331 LR - 20210331 IS - 2050-7518 (Electronic) IS - 2050-750X (Linking) VI - 9 IP - 2 DP - 2021 Jan 21 TI - Dual-enzymatically cross-linked gelatin hydrogel enhances neural differentiation of human umbilical cord mesenchymal stem cells and functional recovery in experimental murine spinal cord injury. PG - 440-452 LID - 10.1039/d0tb02033h [doi] AB - Recently, an advanced stem cell and tissue engineering approach has been recognized as an emerging and fascinating strategy to promote neural repair in spinal cord injury (SCI). Hydrogels can be properly engineered to encapsulate cells, enhance cell viability and neural differentiation, and provide the advantage of flexible adaptation to irregular defects. In this study, a dual-enzymatically cross-linked gelatin hydrogel with hydrogen horseradish peroxidase (HRP) and galactose oxidase (GalOx) was proposed to combine human umbilical cord mesenchymal stem cells (hUC-MSCs) for facilitating nerve regeneration post-SCI. In vitro, hUC-MSCs in this 3D gelatin hydrogel displayed good viability, proliferation, and neuronal differentiation. To further evaluate the neural regeneration effect of hUC-MSCs loaded into gelatin hydrogels in vivo, a clinically-relevant and force-controlled contusion model of mouse spinal cords was established. We found that implantation of a hydrogel loaded with hUC-MSCs significantly promoted the motor function recovery evaluated by Basso Mouse Scale (BMS) and footprint tests. Further histological analysis showed that the hydrogel and hUC-MSC combined transplantation dramatically decreased inflammation, inhibited apoptosis and promoted neurogenesis. Overall, implantation of this dual-enzymatically cross-linked and MSC-laden 3D gelatin hydrogel is a promising therapeutic strategy for SCI treatment. FAU - Yao, Minghao AU - Yao M AUID- ORCID: 0000-0002-2232-0991 AD - School of Life Science, Zhengzhou University, 100 Science Road, Zhengzhou 450001, P. R. China. guanfangxia@126.com yao453343550@126.com. FAU - Li, Jinrui AU - Li J AD - School of Life Science, Zhengzhou University, 100 Science Road, Zhengzhou 450001, P. R. China. guanfangxia@126.com yao453343550@126.com. FAU - Zhang, Junni AU - Zhang J AD - School of Life Science, Zhengzhou University, 100 Science Road, Zhengzhou 450001, P. R. China. guanfangxia@126.com yao453343550@126.com. FAU - Ma, Shanshan AU - Ma S AD - School of Life Science, Zhengzhou University, 100 Science Road, Zhengzhou 450001, P. R. China. guanfangxia@126.com yao453343550@126.com. FAU - Wang, Luyu AU - Wang L AD - School of Life Science, Zhengzhou University, 100 Science Road, Zhengzhou 450001, P. R. China. guanfangxia@126.com yao453343550@126.com. FAU - Gao, Feng AU - Gao F AD - School of Life Science, Zhengzhou University, 100 Science Road, Zhengzhou 450001, P. R. China. guanfangxia@126.com yao453343550@126.com. FAU - Guan, Fangxia AU - Guan F AD - School of Life Science, Zhengzhou University, 100 Science Road, Zhengzhou 450001, P. R. China. guanfangxia@126.com yao453343550@126.com and Institute of Neuroscience, Zhengzhou University, Zhengzhou 450000, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Mater Chem B JT - Journal of materials chemistry. B JID - 101598493 RN - 0 (Hydrogels) SB - IM MH - Animals MH - Humans MH - Hydrogels/*chemistry MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Mice MH - Spinal Cord Injuries/*therapy MH - Umbilical Cord/cytology/metabolism EDAT- 2020/12/09 06:00 MHDA- 2021/04/01 06:00 CRDT- 2020/12/08 12:32 PHST- 2020/12/09 06:00 [pubmed] PHST- 2021/04/01 06:00 [medline] PHST- 2020/12/08 12:32 [entrez] AID - 10.1039/d0tb02033h [doi] PST - ppublish SO - J Mater Chem B. 2021 Jan 21;9(2):440-452. doi: 10.1039/d0tb02033h.