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

IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS
Yijing Zhao, Yihe Wang, Zehao Chen, Haoyu Sheng, Zige Jiang, Liwei Chai, Luyao Zhang, Yan Song, Yijun Zhou, Dexiang Liu* and Zhen Wang*, 
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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.

Abstract Image

含H2S预处理间充质基质细胞外囊泡的三维打印明胶甲基丙烯酰支架促进脊髓损伤大鼠神经元再生。
背景:脊髓损伤(SCI)引起不可逆的运动和感觉缺陷,有效治疗有限。间充质基质细胞(MSCs)主要通过细胞外囊泡(EVs)发挥治疗作用。以硫化氢(H2S)供体预处理MSCs可增强ev的治疗潜力。目的:本研究旨在开发一种3d打印明胶甲基丙烯酰(GelMA)支架,负载h2s预处理的msc衍生ev (h2s - ev),以促进SCI患者的运动功能恢复。方法:从NaHS (H2S供体)预处理的MSCs中分离H2S- ev,并将其纳入3D打印的GelMA支架(3D/GelMA/EVs)中。支架力学性能和h2s - ev。在大鼠脊髓损伤模型中评价支架的治疗效果。结果:MiRNA芯片显示,在h2s - ev中,miR-7a-5p是上调最多的MiRNA。3D/GelMA/EVs支架具有合适的弹性模量和多孔结构,可实现EVs的持续局部释放。在体内,支架可显著改善脊髓损伤大鼠的运动功能恢复。结论:这些结果表明h2s - ev是miR-7a-5p治疗SCI的重要工具,3D/GelMA/ ev支架是理想的干预SCI的生物材料。
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来源期刊
ACS Biomaterials Science & Engineering
ACS Biomaterials Science & Engineering Materials Science-Biomaterials
CiteScore
10.30
自引率
3.40%
发文量
413
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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