Mesenchymal stem cell-laden double-network hydrogel nerve guidance conduits for peripheral nerve injury repair

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2025-09-19 DOI:10.1016/j.bioactmat.2025.08.018

Junghyun Kim, Junggeon Park, Seungjun Lee, Chiseon Ryu, Jongdarm Yi, Goeun Choe, Changhan Jo, Jae Young Lee

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Abstract

To enhance the repair of peripheral nerve injuries (PNIs), various nerve guidance conduits (NGCs) have been developed by integrating topological, biochemical, and cellular cues. Hydrogel-based NGCs are particularly promising owing to their unique tissue-mimicking characteristics, such as high water content, softness, and porosity. However, their weak mechanical strength and insufficient biological activity limits their application. Therefore, in this study, we aimed to develop NGCs by encapsulating human umbilical cord-derived mesenchymal stem cells (ucMSCs) in double-network (DN) hydrogel conduits for improved peripheral nerve regeneration. A DN hydrogel, fabricated via sequential photo- and ionic-crosslinking of 15 % gelatin methacrylate and 1 % alginate, exhibited excellent rheological and mechanical properties, including fatigue resistance, suture retention, and kink resistance. In a rat sciatic defect model, ucMSC-encapsulated DN NGCs demonstrated significantly improved functional and structural recovery compared to medical silicone and non-cellular hydrogel NGCs. Quantitative assessments revealed that the MSC-laden NGC group exhibited superior functional recovery, as indicated by footprint analysis, electromyography, thermal withdrawal latency, and muscle weight restoration. Moreover, histological analysis and transmission electron microscopy confirmed significantly enhanced axonal regeneration and myelination in the MSC-laden NGC group (axon diameter and myelin thickness). Overall, our results indicate that the MSC-laden hydrogel NGCs can serve as a novel platform to treat PNIs and function as effective stem cell delivery scaffolds for the regeneration of various tissues, such as the skin, tendons, and muscles.

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载间充质干细胞双网水凝胶神经引导导管修复周围神经损伤

为了促进周围神经损伤（PNIs）的修复，通过整合拓扑、生化和细胞信号，开发了各种神经引导导管（NGCs）。基于水凝胶的NGCs由于其独特的组织模拟特性（如高含水量、柔软度和孔隙度）而特别有前景。但其机械强度弱，生物活性不足，限制了其应用。因此，在本研究中，我们旨在通过将人脐带来源的间充质干细胞（ucMSCs）包裹在双网络（DN）水凝胶导管中来培养NGCs，以促进周围神经再生。由15%的甲基丙烯酸明胶和1%的海藻酸盐通过顺序光交联和离子交联制备的DN水凝胶，具有优异的流变学和力学性能，包括抗疲劳、保持缝线和抗扭结性能。在大鼠坐骨缺损模型中，与医用硅胶和非细胞水凝胶NGCs相比，ucmsc包封的DN NGCs表现出显著改善的功能和结构恢复。定量评估显示，通过足迹分析、肌电图、热退出潜伏期和肌肉重量恢复，msc -负载的NGC组表现出更好的功能恢复。此外，组织学分析和透射电镜证实，在msc负载的NGC组，轴突再生和髓鞘形成显著增强（轴突直径和髓鞘厚度）。总之，我们的研究结果表明，装载msc的水凝胶NGCs可以作为治疗PNIs的新平台，并作为有效的干细胞递送支架，用于各种组织（如皮肤、肌腱和肌肉）的再生。

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.