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 

机构地区：[1]State Key Laboratory of Pharmaceutical Biotechnology,Division of Sports Medicine and Adult Reconstructive Surgery,Department of Orthopedic Surgery,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,321 Zhongshan Road,Nanjing,210008,Jiangsu,PR China [2]Branch of National Clinical Research Center for Orthopedics,Sports Medicine and Rehabilitation,PR China [3]Co-innovation Center of Neuroregeneration,Nantong University,9 Seyuan Road,Nantong,226019,Jiangsu,PR China [4]Articular Orthopaedics,The Third Affiliated Hospital of Soochow University,185 Juqian Road,Changzhou,213003,Jiangsu,PR China

出　　处：《Bioactive Materials》2023年第6期477-496,共20页生物活性材料（英文）

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).

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 mechanisms.Lines of evidence have shown that hypoxia-induced overproduction of ROS in bone defect region has a major impact on delaying bone regeneration.However,replenishing excess oxygen in a short time cause high oxygen tension that affect the activity of osteoblast precursor cells.Therefore,reasonably restoring the hypoxic condition of bone microenvironment is essential for facilitating bone repair.Herein,we designed ROS scavenging and responsive prolonged oxygen-generating hydrogels(CPP-L/GelMA)as a“bone microenvironment regulative hydrogel”to reverse the hypoxic microenvironment in bone defects region.CPP-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 hydrogels.Under 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 weeks.The prolonged oxygen enriched microenvironment generated by CPP-L/GelMA hydrogel significantly enhanced angiogenesis and osteogenesis while inhibited osteoclastogenesis.Finally,CPP-L/GelMA showed excellent bone regeneration effect in a mice skull defect model through the Nrf2-BMAL1-autophagy pathway.Hence,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.

关 键 词：Bone defect Hypoxic microenvironment Reactive oxygen species responsiveness Prolonged oxygen generation Brain and muscle arnt-like protein 1 

分 类 号：R318[医药卫生—生物医学工程]