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生物活性材料(英文) 2023年第4期22卷 274-290页

作者： Yibo Ying Zhiyang Huang Yurong Tu Qiuji Wu Zhaoyu Li Yifan Zhang Huilei Yu Annian Zeng Hanzhi Huang Jiahui Ye Weiyang Ying Min Chen Zhiyi Feng Ziyue Xiang Qingsong Ye Sipin Zhu Zhouguang Wang School of Pharmaceutical Science Wenzhou Medical UniversityWenzhouZhejiang325000China Department of Orthopaedics The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Department of Pain Medicine The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou325000ZhejiangChina Center of Regenerative Medicine Renmin Hospital of Wuhan UniversityWuhan460030HubeiChina Massachusetts General Hospital Harvard UniversityBoston02114USA Department of Overseas Education College Jimei UniversityXiamenFujianChina

Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ros well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.

关键词： Shear-thinning hydrogel Dental pulp stem cells Ferroptosis ros-scavenging Synaptic regulation

ros‑scavenging Electroactive Polyphosphazene‑Based Core–Shell Nanofibers for Bone Regeneration

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Advanced Fiber Materials 2022年第4期4卷 894-907页

作者： Yiqian Huang Zhiyun Du Ke Li Wei Jing Pengfei Wei Bo Zhao Yingjie Yu Qing Cai Xiaoping Yang State Key Laboratory of Organic‑Inorganic Composites Beijing Laboratory of Biomedical MaterialsBeijing University of Chemical TechnologyBeijing 100029China Beijing Biosis Healing Biological Technology Co. LtdBeijing 102629China Foshan(Southern China)Institute for New Materials Foshan 528200GuangdongChina

Bone defects are always accompanied by inflammation due to excessive reactive oxygen species(ros)in injured regions,which greatly impedes the regeneration of bone tissues.Although many conductive polymers have been developed to scavenge ros,they are typically non-degradable under physiological conditions,making them unsuitable for in vivo applications.Biodegradable polyorganophosphazenes(POPPs)may serve as potent ros-scavenging biomaterials owing to their versatile chemical structures and ease of functionalization.Herein,a PATGP-type electroactive polyphosphazene with side groups of aniline tetramer and glycine ethyl ester was compared to conventional poly(lactic-co-glycolic acid)(PLGA)in regenerating bone tissues.To conduct in vitro and in vivo evaluations,three kinds of electrospun nanofibrous meshes were prepared:PLGA,PLGA/PATGP blend,and PLGA/PATGP core–shell nanofibers.Among them,PLGA/PATGP core–shell nanofibers outperform the blend and PLGA nanofibers in terms of scavenging ros,promoting osteogenic differentiation,and accelerating neo-bone formation.The continuous PATGP shell on the PLGA/PATGP core–shell nanofiber surface could apparently provide more significant modulation effects on cellular behaviors than the PLGA/PATGP blend nanofibers with PATGP dispersed in the PLGA matrix.Therefore,the core–shell structured PLGA/PATGP nanofibers were envisioned as a promising candidate scaffold for bone tissue engineering.Additionally,the core–shell design paved the way for biomedical applications of functional POPPs in combination with other polymeric biomaterials,without phase separation or difficulty of increasing the molecular weights of POPPs.

关键词： Polyorganophosphazene Bone regeneration ros-scavenging Electroactive Electrospinning

Passively-targeted mitochondrial tungsten-based nanodots for efficient acute kidney injury treatment

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Bioactive Materials 2023年第3期21卷 381-393页

作者： Qiong Huang Yuqi Yang Tianjiao Zhao Qiaohui Chen Min Liu Shuting Ji Yan Zhu Yunrong Yang Jinping Zhang Haixin Zhao Yayun Nan Kelong Ai Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha410008China Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha410078China Hunan Provincial Key Laboratory of Cardiovascular Research Xiangya School of Pharmaceutical SciencesCentral South UniversityChangsha410078China Geriatric Medical Center People’s Hospital of Ningxia Hui Autonomous RegionYinchuan750002China

Acute kidney injury(AKI)can lead to loss of kidney function and a substantial increase in mortality.The burst of reactive oxygen species(ros)plays a key role in the pathological progression of AKI.Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ros in AKI.Antioxidant nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced diseases.However,most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules,the main damage site of AKI.Here,an ultra-small Tungsten-based nanodots(TWNDs)with strong ros scavenging can be very effective for treatment of AKI.TWNDs can reach the tubular site after crossing the glomerular barrier,and enter the mitochondria of the renal tubule without resorting to complex active targeting strategies.To our knowledge,this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for AKI.Through in-depth study of the therapeutic mechanism,such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ros and increasing mitophagy.In addition,TWNDs can also reduce the infiltration of inflammatory cells.This work provides a new way to passively target mitochondria for AKI,and give inspiration for the treatment of many major diseases closely related to mitochondria,such as myocardial infarction and cerebral infarction.

关键词： ros-scavenging Anti-inflammatory Acute kidney injury Passively-targeted mitochondrial Tungsten-Based Nanodots

Polydopamine-mediated graphene oxide and nanohydroxyapatite-incorporated conductive scaffold with an immunomodulatory ability accelerates periodontal bone regeneration in diabetes

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Bioactive Materials 2022年第12期7卷 213-227页

作者： Yazhen Li Lu Yang Yue Hou Zhenzhen Zhang Miao Chen Maoxia Wang Jin Liu Jun Wang Zhihe Zhao Chaoming Xie Xiong Lu State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of OrthodonticsWest China Hospital of StomatologySichuan UniversityChengduSichuan610041China Key Lab of Advanced Technologies of Materials Ministry of EducationSchool of Materials Science and EngineeringSouthwest Jiaotong UniversityChengduSichuan610031China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of Oral ImplantologyWest China Hospital of StomatologySichuan UniversityChengduSichuan610041China Lab for Aging Research and National Clinical Research Center for Geriatrics West China HospitalSichuan UniversityChengduSichuan610041China

Regenerating periodontal bone tissues in the aggravated inflammatory periodontal microenvironment under diabetic conditions is a great challenge.Here,a polydopamine-mediated graphene oxide(PGO)and hydroxyapatite nanoparticle(PHA)-incorporated conductive alginate/gelatin(AG)scaffold is developed to accelerate periodontal bone regeneration by modulating the diabetic inflammatory microenvironment.PHA confers the scaffold with osteoinductivity and PGO provides a conductive pathway for the scaffold.The conductive scaffold promotes bone regeneration by transferring endogenous electrical signals to cells and activating Ca2+channels.Moreover,the scaffold with polydopamine-mediated nanomaterials has a reactive oxygen species(ros)-scavenging ability and anti-inflammatory activity.It also exhibits an immunomodulatory ability that suppresses M1 macrophage polarization and activates M2 macrophages to secrete osteogenesis-related cytokines by mediating glycolytic and RhoA/ROCK pathways in macrophages.The scaffold induces excellent bone regeneration in periodontal bone defects of diabetic rats because of the synergistic effects of good conductive,ros-scavenging,anti-inflammatory,and immunomodulatory abilities.This study provides fundamental insights into the synergistical effects of conductivity,osteoinductivity,and immunomodulatory abilities on bone regeneration and offers a novel strategy to design immunomodulatory biomaterials for treatment of immune-related diseases and tissue regeneration.

关键词： Polydopamine Graphene oxide Conductive scaffold ros-scavenging Macrophage polarization