Mohsen Bakhtiari, Mohammad Hossein Ghanian, Reza Moghadasali
{"title":"通过原位形成的Click PEG水凝胶持续和局部递送间充质干细胞来源的细胞外囊泡用于糖尿病肾病治疗。","authors":"Mohsen Bakhtiari, Mohammad Hossein Ghanian, Reza Moghadasali","doi":"10.1021/acsbiomaterials.5c00798","DOIUrl":null,"url":null,"abstract":"<p><p>Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) hold great promise as a cell-free therapy for diabetic nephropathy (DN), but their therapeutic efficacy is limited by rapid clearance from the target site after bolus injection. Herein, an in situ-forming biodegradable hydrogel has been developed for sustained and localized release of EVs into the renal subcapsular space. The MSC-EVs were encapsulated within a synthetic hydrogel based on poly(ethylene glycol) (PEG) during a click reaction between thiol and vinyl sulfone end groups of four-arm PEG macromers at the site of injection in the kidney capsule of DN-modeled mice. The MSC-EV-laden PEG hydrogel gradually swelled and released EVs in a sustained manner over one month. The DN mice treated with the EV-delivering hydrogel exhibited further improved renal function with attenuated histopathological damage, reduced proinflammatory cytokine levels, and lower tubular cell apoptosis compared with the DN mice treated with free EVs. Specifically, the hydrogel-mediated delivery of MSC-EVs could significantly enhance antifibrotic effects of MSC-EVs and even prevent and reverse the progression of renal fibrosis in a DN mouse model, an event that was not observed by the free EV treatment. Collectively, this prolonged delivery system may open a new paradigm for improved EV therapies for various chronic diseases.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sustained and Localized Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles by an In Situ Forming Click PEG Hydrogel for Diabetic Nephropathy Therapy.\",\"authors\":\"Mohsen Bakhtiari, Mohammad Hossein Ghanian, Reza Moghadasali\",\"doi\":\"10.1021/acsbiomaterials.5c00798\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) hold great promise as a cell-free therapy for diabetic nephropathy (DN), but their therapeutic efficacy is limited by rapid clearance from the target site after bolus injection. Herein, an in situ-forming biodegradable hydrogel has been developed for sustained and localized release of EVs into the renal subcapsular space. The MSC-EVs were encapsulated within a synthetic hydrogel based on poly(ethylene glycol) (PEG) during a click reaction between thiol and vinyl sulfone end groups of four-arm PEG macromers at the site of injection in the kidney capsule of DN-modeled mice. The MSC-EV-laden PEG hydrogel gradually swelled and released EVs in a sustained manner over one month. The DN mice treated with the EV-delivering hydrogel exhibited further improved renal function with attenuated histopathological damage, reduced proinflammatory cytokine levels, and lower tubular cell apoptosis compared with the DN mice treated with free EVs. Specifically, the hydrogel-mediated delivery of MSC-EVs could significantly enhance antifibrotic effects of MSC-EVs and even prevent and reverse the progression of renal fibrosis in a DN mouse model, an event that was not observed by the free EV treatment. Collectively, this prolonged delivery system may open a new paradigm for improved EV therapies for various chronic diseases.</p>\",\"PeriodicalId\":8,\"journal\":{\"name\":\"ACS Biomaterials Science & Engineering\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Biomaterials Science & Engineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1021/acsbiomaterials.5c00798\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Biomaterials Science & Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1021/acsbiomaterials.5c00798","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
Sustained and Localized Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles by an In Situ Forming Click PEG Hydrogel for Diabetic Nephropathy Therapy.
Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) hold great promise as a cell-free therapy for diabetic nephropathy (DN), but their therapeutic efficacy is limited by rapid clearance from the target site after bolus injection. Herein, an in situ-forming biodegradable hydrogel has been developed for sustained and localized release of EVs into the renal subcapsular space. The MSC-EVs were encapsulated within a synthetic hydrogel based on poly(ethylene glycol) (PEG) during a click reaction between thiol and vinyl sulfone end groups of four-arm PEG macromers at the site of injection in the kidney capsule of DN-modeled mice. The MSC-EV-laden PEG hydrogel gradually swelled and released EVs in a sustained manner over one month. The DN mice treated with the EV-delivering hydrogel exhibited further improved renal function with attenuated histopathological damage, reduced proinflammatory cytokine levels, and lower tubular cell apoptosis compared with the DN mice treated with free EVs. Specifically, the hydrogel-mediated delivery of MSC-EVs could significantly enhance antifibrotic effects of MSC-EVs and even prevent and reverse the progression of renal fibrosis in a DN mouse model, an event that was not observed by the free EV treatment. Collectively, this prolonged delivery system may open a new paradigm for improved EV therapies for various chronic diseases.
期刊介绍：
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends
Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring
Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration
Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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