Exosomes loaded a smart bilayer-hydrogel scaffold with ROS-scavenging and macrophage-reprogramming properties for repairing cartilage defect  

作　　者：Xiaoqing Lu Shimin Dai Benzhao Huang Shishuo Li Peng Wang Zhibo Zhao Xiao Li Ningbo Li Jie Wen Yunhan Sun Zhentao Man Bing Liu Wei Li 

机构地区：[1]Department of Joint Surgery,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan,Shandong,250021,PR China [2]School of Stomatology,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan,Shandong,250117,PR China [3]College of Sports Medicine and Rehabilitation,Shandong First Medical University&Shandong Academy of Medical Sciences,Taian,Shandong,271016,PR China [4]Medical Science and Technology Innovation Center,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan,Shandong,250117,PR China [5]Endocrine and Metabolic Diseases Hospital of Shandong First Medical University,Shandong Institute of Endocrine and Metabolic Diseases,Jinan,Shandong,250062,PR China

出　　处：《Bioactive Materials》2024年第8期137-153,共17页生物活性材料（英文）

基　　金：supported by National Natural Science Foundation of China(Nos.52002223,81672185 and 81702152);Key Technology Research and Development Program of Shandong(Major Science and Technology Innovation Project)(2020CXGC010502);Taishan Scholar Foundation of Shandong Province(No.tsqn202211348);the Shandong Province Natural Science Foundation(Grant Nos.ZR2022MH222 and ZR2023MH209).

摘　　要：Enhancing the regeneration of cartilage defects remains challenging owing to limited innate self-healing as well as acute inflammation arising from the overexpression of reactive oxygen species(ROS)in post-traumatic microenvironments.Recently,stem cell-derived exosomes(Exos)have been developed as potential cell-free therapy for cartilage regeneration.Although this approach promotes chondrogenesis,it neglects the emerging inflammatory microenvironment.In this study,a smart bilayer-hydrogel dual-loaded with sodium diclofenac(DC),an anti-inflammatory drug,and Exos from bone marrow-derived mesenchymal stem cells was developed to mitigate initial-stage inflammation and promote late-stage stem-cell recruitment and chondrogenic differentiation.First,the upper-hydrogel composed of phenylboronic-acid-crosslinked polyvinyl alcohol degrades in response to elevated levels of ROS to release DC,which mitigates oxidative stress,thus reprogramming macrophages to the pro-healing state.Subsequently,Exos are slowly released from the lower-hydrogel composed of hyaluronic acid into an optimal microenvironment for the stimulation of chondrogenesis.Both in vitro and in vivo assays confirmed that the dual-loaded bilayer-hydrogel reduced post-traumatic inflammation and enhanced cartilage regeneration by effectively scavenging ROS and reprogramming macrophages.The proposed platform provides multi-staged therapy,which allows for the optimal harnessing of Exos as a therapeutic for cartilage regeneration.

关 键 词：EXOSOMES Hydrogels CARTILAGE Reactive oxygen species MACROPHAGE Inflammation 

分 类 号：R318[医药卫生—生物医学工程] TQ427.26[医药卫生—基础医学]