Bone microenvironment regulative hydrogels with ROS scavenging and prolonged oxygen-generating for enhancing bone repair

作     者：Han Sun Juan Xu Yangyufan Wang Siyu Shen Xingquan Xu Lei Zhang Qing Jiang 

作者机构：State Key Laboratory of Pharmaceutical BiotechnologyDivision of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical School321 Zhongshan RoadNanjing210008JiangsuPR China Branch of National Clinical Research Center for OrthopedicsSports Medicine and RehabilitationPR China Co-innovation Center of NeuroregenerationNantong University9 Seyuan RoadNantong226019JiangsuPR China Articular OrthopaedicsThe Third Affiliated Hospital of Soochow University185 Juqian RoadChangzhou213003JiangsuPR China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2023年第24卷第6期

页      面：477-496页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 08[工学] 0836[工学-生物工程] 

基　　金：supported by National Science Foundation of China(Grant No.32271409,82002370,31800806) National Basic Research Program of China(2021YFA1201404) China Postdoctoral Science Foundation(Grant No.2019M661806) Major Project of NSFC(81991514) Natural Science Foundation of Jiangsu Province(Grant No.BK20200117) Jiangsu postdoctoral research support project(Grant No.2021K059A) Program of Innovation and Entrepreneurship of Jiangsu Province,Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation and Jiangsu Provincial Key Medical Talent Foundation,the Fundamental Research Funds for the Central Universities(14380493,14380494) Changzhou Sci&Tech Program(Grant No.CJ20220103) 

主　　题：Bone defect Hypoxic microenvironment Reactive oxygen species responsiveness Prolonged oxygen generation Brain and muscle arnt-like protein 1 

摘      要：Large bone defects resulting from fractures and disease are a major clinical challenge,being often unable to heal spontaneously by the body’s repair *** of evidence have shown that hypoxia-induced overproduction of ROS in bone defect region has a major impact on delaying bone ***,replenishing excess oxygen in a short time cause high oxygen tension that affect the activity of osteoblast precursor ***,reasonably restoring the hypoxic condition of bone microenvironment is essential for facilitating bone ***,we designed ROS scavenging and responsive prolonged oxygen-generating hydrogels(CPP-L/GelMA)as a“bone microenvironment regulative hydrogelto reverse the hypoxic microenvironment in bone defects ***-L/GelMA hydrogels comprises an antioxidant enzyme catalase(CAT)and ROS-responsive oxygen-releasing nanoparticles(PFC@PLGA/PPS)co-loaded liposome(CCP-L)and GelMA *** hypoxic condition,CPP-L/GelMA can release CAT for degrading hydrogen peroxide to generate oxygen and be triggered by superfluous ROS to continuously release the oxygen for more than 2 *** prolonged oxygen enriched microenvironment generated by CPP-L/GelMA hydrogel significantly enhanced angiogenesis and osteogenesis while inhibited ***,CPP-L/GelMA showed excellent bone regeneration effect in a mice skull defect model through the Nrf2-BMAL1-autophagy ***,CPP-L/GelMA,as a bone microenvironment regulative hydrogel for bone tissue respiration,can effectively scavenge ROS and provide prolonged oxygen supply according to the demand in bone defect region,possessing of great clinical therapeutic potential.