PDF(Pubmed)
Abstract：
Peripheral nerve injury is a prevalent clinical problem that often leads to lifelong disability and reduced quality of life. Although peripheral nerves can regenerate, recovery after severe injury is slow and incomplete. The current gold standard treatment, autologous nerve transplantation, has limitations including donor site morbidity and poor functional outcomes, highlighting the need for improved repair strategies. We developed a reproducible in vitro hollow channel collagen gel construct to investigate peripheral nerve regeneration (PNR) by exploring the influence of key extracellular matrix (ECM) proteins on axonal growth and regeneration. Channels were coated with ECM proteins: collagen IV, laminin, or fibronectin and seeded with dorsal root ganglia (DRG) collected from E16 rat embryos to compare the ability of the ECM proteins to enhance axonal growth. Robust axonal extension and Schwann cell (SC) infiltration were observed in fibronectin-coated channels, suggesting its superiority over other ECM proteins. Differential effects of ECM proteins on axons and SCs indicated direct growth stimulation beyond SC-mediated guidance. In vitro laceration injury modeling further confirmed fibronectin\'s superior pro-regenerative effects, showcasing its potential in enhancing axonal regrowth post-injury. Advancing in vitro modeling that closely replicates native microenvironments will accelerate progress in overcoming the limitations of current nerve repair approaches.
摘要：
周围神经损伤是一个普遍的临床问题，通常会导致终身残疾和生活质量下降。虽然周围神经可以再生，严重损伤后恢复缓慢且不完全。目前的黄金标准治疗，自体神经移植,具有局限性，包括供体部位的发病率和不良的功能结果，强调需要改进修复策略。我们开发了一种可重复的体外中空通道胶原凝胶结构，通过探索关键的细胞外基质（ECM）蛋白对轴突生长和再生的影响来研究周围神经再生（PNR）。通道涂有ECM蛋白：胶原蛋白IV，层粘连蛋白,或纤连蛋白，并用从E16大鼠胚胎中收集的背根神经节（DRG）接种，以比较ECM蛋白增强轴突生长的能力。在纤连蛋白包被的通道中观察到稳健的轴突延伸和雪旺氏细胞（SC）浸润，表明其优于其他ECM蛋白。ECM蛋白对轴突和SC的差异作用表明直接生长刺激超出了SC介导的指导。体外裂伤模型进一步证实了纤连蛋白的优越的促再生作用，展示了其增强损伤后轴突再生的潜力。推进紧密复制天然微环境的体外建模将加速克服当前神经修复方法局限性的进展。
