PMID- 37536642 OWN - NLM STAT- MEDLINE DCOM- 20230821 LR - 20230821 IS - 1873-3476 (Electronic) IS - 0378-5173 (Linking) VI - 643 DP - 2023 Aug 25 TI - Berberine-loaded MSC-derived sEVs encapsulated in injectable GelMA hydrogel for spinal cord injury repair. PG - 123283 LID - S0378-5173(23)00703-2 [pii] LID - 10.1016/j.ijpharm.2023.123283 [doi] AB - After spinal cord injury (SCI), local inflammatory response and fibrous scar formation severely hinder nerve regeneration. Berberine (Ber) has a powerful regulatory effect on the local microenvironment, but its limited solubility and permeability through the blood-brain barrier severely limit its systemic efficacy. Human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived small extracellular vesicles (sEVs) are natural nanocarriers with high cargo loading capacity, and can cross the blood-brain barrier. Most importantly, sEVs can improve drug solubility and drug utilization. Therefore, they can overcome many defects of Ber application. This experiment aimed to design a Ber-carrying hUC-MSCs-derived sEVs and GelMA hydrogel. Ber was loaded into sEVs (sEVs-Ber) by ultrasonic co-incubation with a drug loading capacity (LC) of 15.07%. The unhindered release of up to 80% of sEVs-Ber from GelMA hydrogel was accomplished for up to 14 days. And they could be directly absorbed by local cells of injury, allowing for direct local delivery of the drug and enhancing its efficacy. The experimental results confirmed injecting GelMA-sEVs-Ber into spinal cord defects could exert anti-inflammatory effects by regulating the expression of inflammatory factors. It also demonstrated the anti-fibrotic effect of Ber in SCI for the first time. The modulatory effects of sEVs and Ber on the local microenvironment significantly promoted nerve regeneration and recovery of motor function in post-SCI rats. These results demonstrated that the GelMA-sEVs-Ber dual carrier system is a promising therapeutic strategy for SCI repair. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Wang, Heng AU - Wang H AD - Department of Orthopedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China. Electronic address: wheng2022@126.com. FAU - Tang, Qin AU - Tang Q AD - Department of Orthopedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China. FAU - Lu, Yang AU - Lu Y AD - Department of Orthopedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China. FAU - Chen, Cheng AU - Chen C AD - Department of Orthopedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China. FAU - Zhao, Yu-Lin AU - Zhao YL AD - Department of Orthopedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China. FAU - Xu, Tao AU - Xu T AD - Department of Orthopedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China. Electronic address: 1595803595@qq.com. FAU - Yang, Chang-Wei AU - Yang CW AD - Department of Orthopedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China. Electronic address: 2113320247@stmail.ntu.edu.cn. FAU - Chen, Xiao-Qing AU - Chen XQ AD - Department of Orthopedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China. Electronic address: xq.c@live.com. LA - eng PT - Journal Article DEP - 20230801 PL - Netherlands TA - Int J Pharm JT - International journal of pharmaceutics JID - 7804127 RN - 0 (Hydrogels) RN - 0I8Y3P32UF (Berberine) SB - IM MH - Rats MH - Humans MH - Animals MH - Hydrogels/metabolism MH - *Berberine/metabolism MH - Rats, Sprague-Dawley MH - *Spinal Cord Injuries/drug therapy MH - *Extracellular Vesicles/metabolism MH - Spinal Cord/metabolism OTO - NOTNLM OT - Berberine OT - Extracellular vesicles OT - Fibrosis OT - Hydrogel OT - Inflammation OT - Spinal cord injury COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/08/04 01:07 MHDA- 2023/08/21 06:42 CRDT- 2023/08/03 19:18 PHST- 2023/05/17 00:00 [received] PHST- 2023/07/08 00:00 [revised] PHST- 2023/07/28 00:00 [accepted] PHST- 2023/08/21 06:42 [medline] PHST- 2023/08/04 01:07 [pubmed] PHST- 2023/08/03 19:18 [entrez] AID - S0378-5173(23)00703-2 [pii] AID - 10.1016/j.ijpharm.2023.123283 [doi] PST - ppublish SO - Int J Pharm. 2023 Aug 25;643:123283. doi: 10.1016/j.ijpharm.2023.123283. Epub 2023 Aug 1.