PMID- 32633057 OWN - NLM STAT- MEDLINE DCOM- 20210929 LR - 20210929 IS - 1932-7005 (Electronic) IS - 1932-6254 (Linking) VI - 14 IP - 9 DP - 2020 Sep TI - Control the fate of human umbilical cord mesenchymal stem cells with dual-enzymatically cross-linked gelatin hydrogels for potential applications in nerve regeneration. PG - 1261-1271 LID - 10.1002/term.3098 [doi] AB - Stem-cell-based therapy is a promising strategy to treat challenging neurological diseases, while its application is hindered primarily by the low viability and uncontrolled differentiation of stem cell. Hydrogel can be properly engineered to share similar characteristics with the target tissue, thus promoting cell viability and directing cell differentiation. In this study, we proposed a new dual-enzymatically cross-linked and injectable gelatin hydrogel for regulating survival, proliferation, and differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) in a three-dimensional matrix. This injectable gelatin hydrogel was formed by oxidative coupling of gelatin-hydroxyphenyl acid conjugates catalyzed by hydrogen horseradish peroxidase (HRP) and choline oxidase (ChOx). Modulus and H(2) O(2) release can be well controlled by ChOx activity. Results from calcein-AM/PI staining and Ki67 immunofluorescence tests demonstrated that the survival and proliferation behavior of hUC-MSCs were highly enhanced in HRP(1U) ChOx(0.25U) hydrogel with lower modulus and less H(2) O(2) release compared with other groups. Attractively, the expression of neuron-specific markers beta-III tubulin, neurofilament light chain (NFL), and synapsin-1 was significantly increased in HRP(1U) ChOx(0.25U) hydrogel as well. Additionally, in vitro hemolysis test and in vivo HE staining data highlighted the good biocompatibility. Undoubtedly, this injectable gelatin hydrogel's ability to control hUC-MSCs' fate holds enormous potentials in nervous disorders' therapy and nerve regeneration. CI - (c) 2020 John Wiley & Sons, Ltd. FAU - Li, Jinrui AU - Li J AD - School of Life Science, Zhengzhou University, Zhengzhou, P. R. China. FAU - Gao, Feng AU - Gao F AD - School of Life Science, Zhengzhou University, Zhengzhou, P. R. China. FAU - Ma, Shanshan AU - Ma S AUID- ORCID: 0000-0002-0780-4568 AD - School of Life Science, Zhengzhou University, Zhengzhou, P. R. China. FAU - Zhang, Yanting AU - Zhang Y AD - School of Life Science, Zhengzhou University, Zhengzhou, P. R. China. FAU - Zhang, Junni AU - Zhang J AD - School of Life Science, Zhengzhou University, Zhengzhou, P. R. China. FAU - Guan, Fangxia AU - Guan F AD - School of Life Science, Zhengzhou University, Zhengzhou, P. R. China. FAU - Yao, Minghao AU - Yao M AUID- ORCID: 0000-0002-2232-0991 AD - School of Life Science, Zhengzhou University, Zhengzhou, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200713 PL - England TA - J Tissue Eng Regen Med JT - Journal of tissue engineering and regenerative medicine JID - 101308490 RN - 0 (Biocompatible Materials) RN - 0 (Cross-Linking Reagents) RN - 0 (Hydrogels) RN - 0 (Nerve Tissue Proteins) RN - 059QF0KO0R (Water) RN - 9000-70-8 (Gelatin) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Animals MH - Biocompatible Materials/pharmacology MH - Cell Death/drug effects MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Cross-Linking Reagents/*pharmacology MH - Elastic Modulus MH - Gelatin/chemical synthesis/chemistry/*pharmacology MH - Hemolysis/drug effects MH - Humans MH - Hydrogels/*pharmacology MH - Hydrogen Peroxide/chemistry MH - Mesenchymal Stem Cells/*cytology MH - Mice, Inbred C57BL MH - *Nerve Regeneration/drug effects MH - Nerve Tissue Proteins/metabolism MH - Neurons/cytology/drug effects MH - Swine MH - Time Factors MH - Umbilical Cord/*cytology MH - Water/chemistry OTO - NOTNLM OT - dual-enzymatically cross-linked gelatin hydrogels OT - human umbilical cord mesenchymal stem cells OT - neural differentiation OT - three-dimensional culture EDAT- 2020/07/08 06:00 MHDA- 2021/09/30 06:00 CRDT- 2020/07/08 06:00 PHST- 2020/04/15 00:00 [received] PHST- 2020/06/29 00:00 [revised] PHST- 2020/07/01 00:00 [accepted] PHST- 2020/07/08 06:00 [pubmed] PHST- 2021/09/30 06:00 [medline] PHST- 2020/07/08 06:00 [entrez] AID - 10.1002/term.3098 [doi] PST - ppublish SO - J Tissue Eng Regen Med. 2020 Sep;14(9):1261-1271. doi: 10.1002/term.3098. Epub 2020 Jul 13.