PMID- 37255101 OWN - NLM STAT- MEDLINE DCOM- 20230831 LR - 20230921 IS - 2051-6355 (Electronic) IS - 2051-6347 (Linking) VI - 10 IP - 9 DP - 2023 Aug 29 TI - Ultrasound-triggered in situ gelation with ROS-controlled drug release for cartilage repair. PG - 3507-3522 LID - 10.1039/d3mh00042g [doi] AB - Cartilage defects are usually caused by acute trauma and chronic degeneration. However, it is still a great challenge to improve the repair of articular cartilage defects due to the limited self-regeneration capacity of such defects. Herein, a novel ROS-responsive in situ nanocomposite hydrogel loaded with kartogenin (KGN) and bone marrow-derived stem cells (BMSCs) was designed and constructed via the enzymatic reaction of fibrinogen and thrombin. Meanwhile, a ROS-responsive thioketal (TK)-based liposome was synthesized to load the chondrogenesis-inducing factor KGN, the bioenzyme thrombin and an ultrasound-sensitive agent PpIX. Under ultrasound stimulation, the TK-based liposome was destroyed, followed by in situ gelation of fibrinogen and thrombin. Moreover, sustained release of KGN was realized by regulating the ultrasound conditions. Importantly, ROS generation and KGN release within the microenvironment of the in situ fibrin hydrogel significantly promoted chondrogenic differentiation of BMSCs via the Smad5/mTOR signalling pathway and effectively improved cartilage regeneration in a rat articular cartilage defect model. Overall, the novel in situ nanocomposite hydrogel with ROS-controlled drug release has great potential for efficient cartilage repair. FAU - Wu, Shunli AU - Wu S AD - Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. bailong@shu.edu.cn. AD - Organoid Research Center, Shanghai University, Shanghai, 200444, China. AD - School of Medicine, Shanghai University, Shanghai 200444, China. AD - School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China. FAU - Zhang, Hao AU - Zhang H AD - Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. bailong@shu.edu.cn. AD - Organoid Research Center, Shanghai University, Shanghai, 200444, China. FAU - Wang, Sicheng AU - Wang S AD - Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. bailong@shu.edu.cn. AD - School of Medicine, Shanghai University, Shanghai 200444, China. AD - Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, China. FAU - Sun, Jinru AU - Sun J AD - Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. bailong@shu.edu.cn. AD - Organoid Research Center, Shanghai University, Shanghai, 200444, China. AD - School of Medicine, Shanghai University, Shanghai 200444, China. FAU - Hu, Yan AU - Hu Y AD - Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. bailong@shu.edu.cn. AD - Organoid Research Center, Shanghai University, Shanghai, 200444, China. AD - Shaoxing Institute of Technology at Shanghai University, Shaoxing, 312000, China. FAU - Liu, Han AU - Liu H AD - Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. bailong@shu.edu.cn. AD - Organoid Research Center, Shanghai University, Shanghai, 200444, China. FAU - Liu, Jinlong AU - Liu J AD - Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. bailong@shu.edu.cn. AD - Organoid Research Center, Shanghai University, Shanghai, 200444, China. FAU - Chen, Xiao AU - Chen X AD - Department of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Zhou, Fengjin AU - Zhou F AD - Department of Orthopaedics, Honghui Hospital, Xi'an Jiao Tong University, Xi'an 710000, China. dr.zhoufj@163.com. FAU - Bai, Long AU - Bai L AD - Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. bailong@shu.edu.cn. AD - Organoid Research Center, Shanghai University, Shanghai, 200444, China. FAU - Wang, Xiuhui AU - Wang X AUID- ORCID: 0000-0002-6031-0380 AD - Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. bailong@shu.edu.cn. AD - Organoid Research Center, Shanghai University, Shanghai, 200444, China. FAU - Su, Jiacan AU - Su J AUID- ORCID: 0000-0001-7080-263X AD - Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. bailong@shu.edu.cn. AD - Organoid Research Center, Shanghai University, Shanghai, 200444, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230829 PL - England TA - Mater Horiz JT - Materials horizons JID - 101623537 RN - 0 (Reactive Oxygen Species) RN - 0 (Liposomes) RN - 0 (Nanogels) RN - EC 3.4.21.5 (Thrombin) RN - 0 (Hydrogels) SB - IM MH - Rats MH - Animals MH - Reactive Oxygen Species/metabolism/pharmacology MH - Drug Liberation MH - Liposomes/metabolism/pharmacology MH - Nanogels MH - Thrombin/metabolism/pharmacology MH - *Mesenchymal Stem Cells/metabolism MH - *Cartilage, Articular/diagnostic imaging/injuries/metabolism MH - Hydrogels EDAT- 2023/05/31 13:12 MHDA- 2023/08/31 06:41 CRDT- 2023/05/31 07:53 PHST- 2023/08/31 06:41 [medline] PHST- 2023/05/31 13:12 [pubmed] PHST- 2023/05/31 07:53 [entrez] AID - 10.1039/d3mh00042g [doi] PST - epublish SO - Mater Horiz. 2023 Aug 29;10(9):3507-3522. doi: 10.1039/d3mh00042g.