Synergistic effects of electrical and chemical cues with biodegradable scaffolds for large peripheral nerve defect regeneration

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2025-03-26 DOI:10.1016/j.bioactmat.2025.03.017

Rosalie Bordett , Sama Abdulmalik , Allen Zennifer , Suranji Wijekoon , Sai Sadhananth Srinivasan , Ergin Coskun , Yeshavanth Kumar Banasavadi Siddegowda , Xiaojun Yu , Sangamesh G. Kumbar

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引用次数: 0

Abstract

Large-gap peripheral nerve injuries (PNI) are often treated with autografts, allografts, or synthetic grafts to facilitate nerve regeneration, but these options are often limited in their availability or functionality. To address these issues, we developed ionically conductive (IC) nerve guidance conduits (NGCs) of sufficient biodegradability, mechanical strength, and bioactivity to support large-gap nerve regeneration. These chitosan-based NGCs release 4-aminopyridine (4-AP) from embedded halloysite nanotubes, and the NGC's IC properties enable transcutaneous electrical stimulation (ES) without invasive electrodes. In vitro, we found scaffolds with ES+4-AP synergistically enhanced Schwann cell adhesion, proliferation, and neurotrophin secretion, significantly improving axonal growth and neurite extension. In vivo, these scaffolds in large-gap PNI boosted neurotrophin levels, myelination, nerve function, and muscle weight while promoting angiogenesis and reducing fibrosis. Upregulated Trk receptors and PI3K/Akt and MAPK pathway highlight the regenerative potential. This study advances understanding of ES-mediated regeneration and supports innovative strategies for nerve and musculoskeletal repair.

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电和化学线索与生物可降解支架在大周围神经缺损再生中的协同作用

大间隙周围神经损伤（PNI）通常通过自体移植物、同种异体移植物或合成移植物来治疗，以促进神经再生，但这些选择通常在可用性或功能上受到限制。为了解决这些问题，我们开发了具有足够生物降解性、机械强度和生物活性的离子导电（IC）神经引导导管（NGCs）来支持大间隙神经再生。这些基于壳聚糖的NGC从嵌入的高岭土纳米管中释放4-氨基吡啶（4-AP），并且NGC的IC特性使经皮电刺激（ES）无需侵入电极。在体外，我们发现含有ES+4-AP的支架可协同增强雪旺细胞的粘附、增殖和神经营养因子的分泌，显著改善轴突生长和神经突延伸。在体内，这些大间隙PNI支架可提高神经营养蛋白水平、髓鞘形成、神经功能和肌肉重量，同时促进血管生成和减少纤维化。Trk受体和PI3K/Akt和MAPK通路的上调凸显了再生潜能。这项研究促进了对es介导的再生的理解，并支持神经和肌肉骨骼修复的创新策略。

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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.