文献类型：期刊文献

英文题名：Rejuvenating Aged Bone Repair through Multihierarchy Reactive Oxygen Species-Regulated Hydrogel

作者：He, Zirui[1,2];Sun, Chuanhao[3];Ma, Yifan[4];Chen, Xi[1,2];Wang, Ying[1,2];Chen, Kai[1,2];Xie, Fangru[1,2];Zhang, Yan[3];Yuan, Yuan[1,2];Liu, Changsheng[1,2]

机构：[1]East China Univ Sci & Technol, Key Lab Ultrafine Mat, Minist Educ, Basic Sci Ctr Project,Natl Nat Sci Fdn China, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Mat Sci & Engn, Key Lab Adv Polymer Mat, Key Lab Ultrafine Mat,Minist Educ, Shanghai 200237, Peoples R China;[4]Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA

年份：2024

卷号：36

期号：9

外文期刊名：ADVANCED MATERIALS

收录：;EI(收录号：20235115239467);WOS:【SCI-EXPANDED(收录号:WOS:001126421000001)】；

基金：Z.R.H. and C.H.S. contributed equally to this work. This work was supported by the National Key Research and Development Program of China (No. SQ2022YFC2400481), the National Nature Science Foundation of China (Grant nos.: 31971264, 32271401, 51873062, 32101151, 32371464), and the Basic Science Center Project of National Natural Science Foundation of China (Grant no.: T2288102). All authors discussed the results commented on the manuscript and approved the final version of this manuscript.

语种：英文

外文关键词：aged bone regeneration; poly(diselenide-carbonate) nanomicelles; ROS-scavenging hydrogel; senescent microenvironment

摘要：Aging exacerbates the dysfunction of tissue regeneration at multiple levels and gradually diminishes individual's capacity to withstand stress, damage, and disease. The excessive accumulation of reactive oxygen species (ROS) is considered a hallmark feature of senescent stem cells, which causes oxidative stress, deteriorates the host microenvironment, and eventually becomes a critical obstacle for aged bone defect repair. Till now, the strategies cannot synchronously and thoroughly regulate intracellular and extracellular ROS in senescent cells. Herein, a multihierarchy ROS scavenging system for aged bone regeneration is developed by fabricating an injectable PEGylated poly(glycerol sebacate) (PEGS-NH2)/poly(gamma-glutamic acid) (gamma-PGA) hydrogel containing rapamycin-loaded poly(diselenide-carbonate) nanomicelles (PSeR). This PSeR hydrogel exhibits highly sensitive ROS responsiveness to the local aged microenvironment and dynamically releases drug-loaded nanomicelles to scavenge the intracellular ROS accumulated in senescent bone mesenchymal stem cells. The PSeR hydrogel effectively tunes the antioxidant function and delays senescence of bone mesenchymal stem cells by safeguarding DNA replication in an oxidative environment, thereby promoting the self-renewal ability and enhancing the osteogenic capacity for aged bone repair in vitro and in vivo. Thus, this multihierarchy ROS-regulated hydrogel provides a new strategy for treating degenerative diseases. The multihierarchy reactive oxygen species regulated system, PEGS-PGA/SeSe/Rapa hydrogel (PSeR) for aged bone regeneration can effectively delay senescence and restore the regenerative function of senescent BMSCs by maintaining the levels of ROS intracellularly and extracellularly. Additionally, the PSeR hydrogel can be injected and rapidly crosslinked in the site of bone defects, presenting a novel therapeutic strategy for addressing age-related bone injuries.image