Mitochondrial-Oriented Injectable Hydrogel Microspheres Maintain Homeostasis of Chondrocyte Metabolism to Promote Subcellular Therapy in Osteoarthritis

作者全名："Chen, Li; Yang, Jianye; Cai, Zhengwei; Huang, Yanran; Xiao, Pengcheng; Chen, Hong; Luo, Xiaoji; Huang, Wei; Cui, Wenguo; Hu, Ning"

作者地址："[Chen, Li; Yang, Jianye; Huang, Yanran; Xiao, Pengcheng; Chen, Hong; Luo, Xiaoji; Huang, Wei; Hu, Ning] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Orthoped Lab, Chongqing 400016, Peoples R China; [Yang, Jianye; Cai, Zhengwei; Huang, Yanran; Xiao, Pengcheng; Cui, Wenguo] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Key Lab Prevent & Treatment Bone & Joint, Shanghai Inst Traumatol & Orthopaed,Sch Med,Dept O, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China"

通信作者："Huang, W; Hu, N (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Orthoped Lab, Chongqing 400016, Peoples R China.; Cui, WG (通讯作者)，Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Key Lab Prevent & Treatment Bone & Joint, Shanghai Inst Traumatol & Orthopaed,Sch Med,Dept O, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China."

来源：RESEARCH

ESI学科分类：　

WOS号：WOS:001193272800001

JCR分区：Q1

影响因子：11

年份：2024

卷号：7

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Subcellular mitochondria serve as sensors for energy metabolism and redox balance, and the dynamic regulation of functional and dysfunctional mitochondria plays a crucial role in determining cells' fate. Selective removal of dysfunctional mitochondria at the subcellular level can provide chondrocytes with energy to prevent degeneration, thereby treating osteoarthritis. Herein, to achieve an ideal subcellular therapy, cartilage affinity peptide (WYRGRL)-decorated liposomes loaded with mitophagy activator (urolithin A) were integrated into hyaluronic acid methacrylate hydrogel microspheres through microfluidic technology, named HM@WY-Lip/UA, that could efficiently target chondrocytes and selectively remove subcellular dysfunctional mitochondria. As a result, this system demonstrated an advantage in mitochondria function restoration, reactive oxygen species scavenging, cell survival rescue, and chondrocyte homeostasis maintenance through increasing mitophagy. In a rat post-traumatic osteoarthritis model, the intra-articular injection of HM@WYLip/UA ameliorated cartilage matrix degradation, osteophyte formation, and subchondral bone sclerosis at 8 weeks. Overall, this study indicated that HM@WY-Lip/UA provided a protective effect on cartilage degeneration in an efficacious and clinically relevant manner, and a mitochondrial-oriented strategy has great potential in the subcellular therapy of osteoarthritis."

基金机构："National Natural Science Foundation of China [82072443, 82372425]; China Postdoctoral Science Foundation [2022M-710557]; Natural Science Foundation of Chongqing, China [CSTB2023NSCQ-BHX0011]; Young Excellent Science and Technology Talent Project of the First Affiliated Hospital of Chongqing Medical University [ZYRC2022-05]"

基金资助正文："Funding: This research was funded by the National Natural Science Foundation of China (82072443 and 82372425) , the China Postdoctoral Science Foundation (Grant No. 2022M-710557) , the Natural Science Foundation of Chongqing, China (Grant No. CSTB2023NSCQ-BHX0011) , and the Young Excellent Science and Technology Talent Project of the First Affiliated Hospital of Chongqing Medical University (Grant No. ZYRC2022-05) . Downloaded from https://spj.science.org"