<br>基于 Bredigite 的生物活性神经引导导管，用于促愈合巨噬细胞极化和周围神经再生,Advanced Healthcare Materials

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基于 Bredigite 的生物活性神经引导导管，用于促愈合巨噬细胞极化和周围神经再生
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-11-16 , DOI: 10.1002/adhm.202302994
Yaowei Xuan ₁ , Lin Li ₁ , Xuelai Yin ₂ , Dongming He ₃ , Siyao Li ₁ , Chenping Zhang ₂ , Yuan Yin ₁ , Wanlin Xu ₂ , Zhen Zhang ₂

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因创伤或慢性疾病而受损的周围神经的结构和功能愈合仍然是主要的临床挑战，需要开发有效的神经引导导管（NGC）。本研究研究了一种基于 bredigite （BRT， Ca₇MgSi₄O₁₆）生物陶瓷的 NGC 制造策略，用于治疗周围神经损伤。在这里，BRT 生物陶瓷显示出良好的生物相容性和 Ca²⁺、Mg²⁺ 和 Si⁴⁺ 离子的可持续释放。BRT 提取物和 BRT 掺入的静电纺丝膜均可促进 RSC96 细胞的增殖和髓鞘形成电位，并加速人脐静脉内皮细胞的血管形成。值得注意的是，BRT 在 LPS 诱导的炎症刺激下促进 RAW 264.7 细胞极化为促愈合表型。更重要的是，BRT 激活的巨噬细胞反过来促进 RSC96 细胞迁移和髓鞘再生。在大鼠坐骨神经缺损模型中，在植入后 12 周观察到电生理性能改善和腓肠肌萎缩减轻。进一步的实验证实，负载 BRT 的 NGC 促进轴突再生和血运重建，具有高度的 M2 样巨噬细胞浸润。这些发现支持 BRT 对创造促愈合免疫微环境和协调与功能性神经再生相关的多细胞过程的有益作用，表明合理设计的生物陶瓷作为安全、有效和经济的周围神经修复材料的潜力。

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Bredigite-Based Bioactive Nerve Guidance Conduit for Pro-Healing Macrophage Polarization and Peripheral Nerve Regeneration

Structural and functional healing of peripheral nerves damaged by trauma or chronic disease remain major clinical challenges, requiring the development of an effective nerve guidance conduit (NGC). The present study investigates a NGC fabrication strategy based on bredigite (BRT, Ca₇MgSi₄O₁₆) bioceramic for the treatment of peripheral nerve injury. Here, BRT bioceramic shows good biocompatibility and sustainable release of Ca²⁺, Mg²⁺, and Si⁴⁺ ions. Both BRT extracts and BRT-incorporating electrospun membranes promote the proliferation and myelination potential of RSC96 cells, as well as accelerate vascular formation by human umbilical vein endothelial cells. Notably, BRT facilitates RAW 264.7 cell polarization to the pro-healing phenotype under LPS-induced inflammatory stimulation. More importantly, the macrophages activated by BRT in turn promote RSC96 cell migration and remyelination. In a rat sciatic nerve defect model, improved electrophysiological performance and alleviated gastrocnemius muscle atrophy are observed at 12 weeks post-implantation. Further experiments verify that BRT-loaded NGC facilitates axonal regrowth and revascularization with high M2-like macrophage infiltration. These findings support the beneficial effects of BRT for creating a pro-healing immune microenvironment and orchestrating multicellular processes associated with functional nerve regeneration, indicating the potential of rationally engineered bioceramics as safe, effective, and economical materials for peripheral nerve repair.

更新日期：2023-11-16

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