PMID- 37256923 OWN - NLM STAT- MEDLINE DCOM- 20230613 LR - 20230615 IS - 2373-9878 (Electronic) IS - 2373-9878 (Linking) VI - 9 IP - 6 DP - 2023 Jun 12 TI - Bilayer Silk Fibroin/Sodium Alginate Scaffold Delivered hUC-MSCs to Enhance Skin Scarless Healing and Hair Follicle Regeneration with the IRE1/XBP1 Pathway Inhibition. PG - 3476-3487 LID - 10.1021/acsbiomaterials.3c00059 [doi] AB - Efficient local delivery of mesenchymal stem cells (MSCs) is a decisive factor for their application in regeneration processes. Here, we prepared a biomimetic bilayer silk fibroin/sodium alginate (SF/SA) scaffold to deliver human umbilical mesenchymal stem cells (hUC-MSCs) for wound healing. An SA membrane was prepared by the casting method on the upper layer of the scaffold to simulate the dense epidermal structure. On the lower layer, porous materials simulating the loose structure of the dermis were formed by the freeze-drying method. In vitro, the scaffold was proven to have a high-density pore structure, good swelling property, and suitable degradation rate. The hUC-MSCs could survive on the scaffold for up to 14 days and maintain cell stemness for at least 7 days. In vivo, SF/SA scaffolds loaded with hUC-MSCs (M-SF/SA) were applied to full-thickness defect wounds and compared with the local injection of hUC-MSCs. The M-SF/SA group showed excellent therapeutic efficacy, characterized by induction of macrophage polarization, regulation of TGF-beta expression and collagen components, and enhancement of vascular regeneration, thereby preventing scar formation and promoting hair follicle regeneration. Furthermore, the expression of endoplasmic reticulum stress markers IRE1, XBP1, and CHOP was inhibited significantly in M-SF/SA treatment. In conclusion, the bilayer SF/SA scaffold is an ideal delivery platform for hUC-MSCs, and the M-SF/SA system could locally promote scarless skin healing and hair follicle regeneration by alleviating the IRE1/XBP1 signal pathway. FAU - Dou, Zhaona AU - Dou Z AUID- ORCID: 0000-0003-2862-7385 AD - State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan, Hubei 430070, China. FAU - Qiu, Tong AU - Qiu T AUID- ORCID: 0000-0001-6314-0885 AD - State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan, Hubei 430070, China. FAU - Ren, Yimeng AU - Ren Y AD - School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei 430070, China. FAU - Wang, Xinyu AU - Wang X AD - State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan, Hubei 430070, China. FAU - Wen, Quan AU - Wen Q AD - Yinfeng Academy of Life Science, Yichang Laboratory of Hematopoietic Stem Cells, 1109 Gangxing Sanlu, Jinan, Shandong Province 250100, China. FAU - Shen, Ying AU - Shen Y AD - State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan, Hubei 430070, China. FAU - Wu, Lin AU - Wu L AD - State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan, Hubei 430070, China. FAU - Han, Lei AU - Han L AD - State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan, Hubei 430070, China. FAU - Jiang, Tao AU - Jiang T AD - School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei 430070, China. FAU - Xia, Xinke AU - Xia X AD - Institute of Life Science, Yinfeng Biological Group, High-tech Zone, Jinan, Shandong Province 250100, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230531 PL - United States TA - ACS Biomater Sci Eng JT - ACS biomaterials science & engineering JID - 101654670 RN - 9007-76-5 (Fibroins) RN - 0 (Alginates) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - 0 (XBP1 protein, human) RN - 0 (X-Box Binding Protein 1) SB - IM MH - Humans MH - *Fibroins/pharmacology MH - Hair Follicle MH - Alginates/pharmacology/chemistry MH - Wound Healing MH - *Mesenchymal Stem Cells/physiology MH - Protein Serine-Threonine Kinases MH - X-Box Binding Protein 1/genetics OTO - NOTNLM OT - bilayer silk fibroin/sodium alginate OT - hair follicle regeneration OT - human umbilical mesenchymal stem cells OT - scarless healing OT - the IRE1/XBP1 pathway EDAT- 2023/05/31 19:16 MHDA- 2023/06/13 06:42 CRDT- 2023/05/31 13:52 PHST- 2023/06/13 06:42 [medline] PHST- 2023/05/31 19:16 [pubmed] PHST- 2023/05/31 13:52 [entrez] AID - 10.1021/acsbiomaterials.3c00059 [doi] PST - ppublish SO - ACS Biomater Sci Eng. 2023 Jun 12;9(6):3476-3487. doi: 10.1021/acsbiomaterials.3c00059. Epub 2023 May 31.