{"title":"Three-Dimensional-Printed Gelatin Methacryloyl Scaffold Loaded with Extracellular Vesicles Derived from H2S Preconditioned Mesenchymal Stromal Cells Promotes Neuronal Regeneration in Rats with Spinal Cord Injury","authors":"Yijing Zhao, Yihe Wang, Zehao Chen, Haoyu Sheng, Zige Jiang, Liwei Chai, Luyao Zhang, Yan Song, Yijun Zhou, Dexiang Liu* and Zhen Wang*, ","doi":"10.1021/acsbiomaterials.5c00083","DOIUrl":null,"url":null,"abstract":"<p >Background: spinal cord injury (SCI) causes irreversible motor and sensory deficits with limited effective treatments. Mesenchymal stromal cells (MSCs) exert therapeutic effects largely through extracellular vesicles (EVs). Preconditioning MSCs with a hydrogen sulfide (H<sub>2</sub>S) donor enhance the therapeutic potential of EVs. Objective: this study is aimed to develop a 3D-printed gelatin methacryloyl (GelMA) scaffold loaded with H<sub>2</sub>S-preconditioned MSC-derived EVs (H<sub>2</sub>S-EVs) to promote motor function recovery in SCI. Methods: H<sub>2</sub>S-EVs were isolated from NaHS (an H<sub>2</sub>S donor)-preconditioned MSCs and incorporated into a 3D-printed GelMA scaffold (3D/GelMA/EVs). Scaffold mechanical properties and H<sub>2</sub>S-EVs. The scaffold’s therapeutic efficacy was evaluated in a rat SCI model. Results: MiRNA microarray revealed miR-7a-5p as the most upregulated miRNA in H<sub>2</sub>S-EVs. The 3D/GelMA/EVs scaffold exhibited an appropriate elastic modulus and porous structure, enabling sustained local EVs release. In vivo, the scaffold significantly improved motor function recovery in SCI rats. Conclusion: these results indicated that H<sub>2</sub>S-EVs provided an important therapeutic tool against SCI by miR-7a-5p and 3D/GelMA/EVs scaffolds were ideal biomaterials for the intervention of SCI.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 8","pages":"4898–4914"},"PeriodicalIF":5.5000,"publicationDate":"2025-07-18","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://pubs.acs.org/doi/10.1021/acsbiomaterials.5c00083","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: spinal cord injury (SCI) causes irreversible motor and sensory deficits with limited effective treatments. Mesenchymal stromal cells (MSCs) exert therapeutic effects largely through extracellular vesicles (EVs). Preconditioning MSCs with a hydrogen sulfide (H2S) donor enhance the therapeutic potential of EVs. Objective: this study is aimed to develop a 3D-printed gelatin methacryloyl (GelMA) scaffold loaded with H2S-preconditioned MSC-derived EVs (H2S-EVs) to promote motor function recovery in SCI. Methods: H2S-EVs were isolated from NaHS (an H2S donor)-preconditioned MSCs and incorporated into a 3D-printed GelMA scaffold (3D/GelMA/EVs). Scaffold mechanical properties and H2S-EVs. The scaffold’s therapeutic efficacy was evaluated in a rat SCI model. Results: MiRNA microarray revealed miR-7a-5p as the most upregulated miRNA in H2S-EVs. The 3D/GelMA/EVs scaffold exhibited an appropriate elastic modulus and porous structure, enabling sustained local EVs release. In vivo, the scaffold significantly improved motor function recovery in SCI rats. Conclusion: these results indicated that H2S-EVs provided an important therapeutic tool against SCI by miR-7a-5p and 3D/GelMA/EVs scaffolds were ideal biomaterials for the intervention of SCI.
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:
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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
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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