PMID- 35587044 OWN - NLM STAT- MEDLINE DCOM- 20220805 LR - 20221209 IS - 2192-2659 (Electronic) IS - 2192-2640 (Linking) VI - 11 IP - 15 DP - 2022 Aug TI - Magnesium Oxide/Poly(l-lactide-co-epsilon-caprolactone) Scaffolds Loaded with Neural Morphogens Promote Spinal Cord Repair through Targeting the Calcium Influx and Neuronal Differentiation of Neural Stem Cells. PG - e2200386 LID - 10.1002/adhm.202200386 [doi] AB - Because of the limited regenerative ability of the central nervous system (CNS), effective treatments for spinal cord injury (SCI) are still lacking. After SCI, neuron loss and axon regeneration failure often result in irreversible functional impairment. The calcium overload induced by the N-methyl-D-aspartate receptor (NMDAR) overactivation is critical for cell death in SCI. It has been reported that the magnesium ion (Mg(2+) ) can competitively block the NMDAR and reduce the calcium influx, and that sonic hedgehog (Shh) and retinoic acid (RA) are the critical regulators of neuronal differentiation of endogenous neural stem cells (NSCs). Here, magnesium oxide (MgO)/poly (l-lactide-co-epsilon-caprolactone) (PLCL) scaffold loaded with purmorphamine (PUR, a Shh signaling agonist) and RA is developed and its feasibility in SCI repair is tested. The results showed that the Mg(2+) released from MgO attenuated cell apoptosis by blocking the calcium influx, and the PUR/RA promoted the recruitment and neuronal differentiation of endogenous NSCs, thereby reducing the glial scar formation at the SCI lesion site. Furthermore, implantation of PUR/RA-loaded MgO/PLCL scaffold facilitates the partial recovery of a locomotor function of SCI mouse in vivo. Together, findings from this study imply that PUR/RA-loaded MgO/PLCL scaffold may be a promising biomaterial for the clinical treatment of SCI. CI - (c) 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH. FAU - Xie, Jile AU - Xie J AD - Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 899# Pinghai Road, Suzhou, Jiangsu, 215006, China. FAU - Li, Jiaying AU - Li J AD - Orthopaedic Institute, Medical College, Soochow University, 1# Shizi Road, Suzhou, Jiangsu, 215006, China. FAU - Ma, Jinjin AU - Ma J AD - Orthopaedic Institute, Medical College, Soochow University, 1# Shizi Road, Suzhou, Jiangsu, 215006, China. FAU - Li, Meimei AU - Li M AD - Orthopaedic Institute, Medical College, Soochow University, 1# Shizi Road, Suzhou, Jiangsu, 215006, China. FAU - Wang, Xingran AU - Wang X AD - Orthopaedic Institute, Medical College, Soochow University, 1# Shizi Road, Suzhou, Jiangsu, 215006, China. FAU - Fu, Xinya AU - Fu X AD - Orthopaedic Institute, Medical College, Soochow University, 1# Shizi Road, Suzhou, Jiangsu, 215006, China. FAU - Ma, Yanxia AU - Ma Y AD - Orthopaedic Institute, Medical College, Soochow University, 1# Shizi Road, Suzhou, Jiangsu, 215006, China. FAU - Yang, Huilin AU - Yang H AD - Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 899# Pinghai Road, Suzhou, Jiangsu, 215006, China. AD - Orthopaedic Institute, Medical College, Soochow University, 1# Shizi Road, Suzhou, Jiangsu, 215006, China. FAU - Li, Bin AU - Li B AD - Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 899# Pinghai Road, Suzhou, Jiangsu, 215006, China. AD - Orthopaedic Institute, Medical College, Soochow University, 1# Shizi Road, Suzhou, Jiangsu, 215006, China. FAU - Saijilafu AU - Saijilafu AUID- ORCID: 0000-0003-2290-9808 AD - Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 899# Pinghai Road, Suzhou, Jiangsu, 215006, China. AD - Orthopaedic Institute, Medical College, Soochow University, 1# Shizi Road, Suzhou, Jiangsu, 215006, China. LA - eng PT - Journal Article DEP - 20220603 PL - Germany TA - Adv Healthc Mater JT - Advanced healthcare materials JID - 101581613 RN - 0 (Caproates) RN - 0 (Dioxanes) RN - 0 (Hedgehog Proteins) RN - 0 (Lactones) RN - 3A3U0GI71G (Magnesium Oxide) RN - 56RE988L1R (caprolactone) RN - 95-96-5 (dilactide) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Axons/metabolism MH - Calcium/metabolism MH - Caproates MH - Cell Differentiation MH - Dioxanes MH - Hedgehog Proteins/metabolism/pharmacology MH - Lactones MH - Magnesium Oxide/metabolism/pharmacology MH - Mice MH - *Neural Stem Cells MH - Spinal Cord/pathology MH - *Spinal Cord Injuries/drug therapy/pathology MH - *Spinal Cord Regeneration MH - Tissue Scaffolds OTO - NOTNLM OT - magnesium OT - neural morphogens OT - neuroprotection OT - spinal cord injury EDAT- 2022/05/20 06:00 MHDA- 2022/08/06 06:00 CRDT- 2022/05/19 05:52 PHST- 2022/04/22 00:00 [revised] PHST- 2022/02/18 00:00 [received] PHST- 2022/05/20 06:00 [pubmed] PHST- 2022/08/06 06:00 [medline] PHST- 2022/05/19 05:52 [entrez] AID - 10.1002/adhm.202200386 [doi] PST - ppublish SO - Adv Healthc Mater. 2022 Aug;11(15):e2200386. doi: 10.1002/adhm.202200386. Epub 2022 Jun 3.