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

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Bioactive Materials 2023年第6期24卷 477-496页

作者： Han Sun Juan Xu Yangyufan Wang Siyu Shen Xingquan Xu Lei Zhang Qing Jiang State Key Laboratory of Pharmaceutical Biotechnology Division 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 Orthopedics Sports Medicine and RehabilitationPR China Co-innovation Center of Neuroregeneration Nantong University9 Seyuan RoadNantong226019JiangsuPR China Articular Orthopaedics The Third Affiliated Hospital of Soochow University185 Juqian RoadChangzhou213003JiangsuPR China

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 hydrogel”to 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.

关键词： Bone defect hypoxic microenvironment Reactive oxygen species responsiveness Prolonged oxygen generation Brain and muscle arnt-like protein 1

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Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats

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Bioactive Materials 2021年第8期6卷 2452-2466页

作者： Sipin Zhu Yibo Ying Yan He Xingxing Zhong Jiahui Ye Zhiyang Huang Min Chen Qiuji Wu Yifan Zhang Ziyue Xiang Yurong Tu Weiyang Ying Jian Xiao Xiaokun Li Qingsong Ye Zhouguang Wang Department of Orthopaedics The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang325000China Molecular Pharmacology Research Center School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhouZhejiangChina Department of Pain Medicine The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou325000ZhejiangChina School and Hospital of Stomatology Wenzhou Medical UniversityWenzhou325035China Laboratory of Regenerative Medicine Tianyou HospitalWuhan University of Science and TechnologyWuhan430064China The Department of Cardiology The First Affiliated HospitalSchool of MedicineZhejiang UniversityChina Massachusetts General Hospital Harvard UniversityBoston02114USA Research Units of Clinical Translation of Cell Growth Factors and Diseases Research Chinese Academy of Medical ScienceChina Center of Regenerative Medicine Renmin Hospital of Wuhan UniversityWuhan630060China

Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)*** fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following *** dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement *** purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing *** this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial *** re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of *** a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was ***,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.

关键词： Spinal cord injury Adeno-associated virus Basic fibroblast growth factor Dental pulp stem cell Vascular regulation hypoxic microenvironment

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Analysis of the relationship between liver-qi stagnation and premature ovarian failure based on exosomes

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TMR Integrative Medicine 2021年第26期5卷 1-6页

作者： Chen Yu Jing-Yan Song Hai-Cui Wu Fang Lian Traditional Chinese Medicine College of Shandong University of Traditional Chinese Medicine Jinan Shandong250011China The First Clinical Medical College of Shandong University of Traditional Chinese Medicine Jinan Shandong250011China Reproductive and Genetic Center of Integrated Chinese and Western Medicine affiliated Hospital of Shandong University of Traditional Chinese Medicine Jinan Shandong250014China

The incidence of premature ovarian failure,which is related to women’s excessive pressure and mental tension,has increased in recent *** ovarian failure has become one of the diseases that seriously disturb women’s physical and mental health,and its incidence can be regarded as liver depression and qi *** have an increasing demand for treatment,not only for fertility with the improvement of social living standards and the development of healthcare ***,as small membrane vesicles containing complex RNA and proteins,have the function of mediating cell communication and transmitting information in the pathological state caused by liver-qi *** in the hypoxic microenvironment can protect cells from damage and promote the pathological ***,exosomes in an inflammatory environment can play an active anti-inflammatory *** can reduce the apoptosis of granulosa cells by expressing miRNA and so on to restore ovarian *** purpose of treating premature ovarian failure can be achieved in this *** paper introduced the relationship between the three,discussed the guiding significance of Chinese medicine theories in the treatment of exosomes and premature ovarian failure,and provided new research ideas for the treatment of integrated traditional Chinese medicine and western medicine.

关键词： Liver-qi stagnation Premature ovarian failure Exosomes hypoxic microenvironment Inflammatory reaction

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