PDF(Pubmed)
Abstract：
Traumatic injuries to the peripheral nervous system (PNI) can lead to severe consequences such as paralysis. Unfortunately, current treatments rarely allow for satisfactory functional recovery. The high healthcare costs associated with PNS injuries, worker disability, and low patient satisfaction press for alternative solutions that surpass current standards. For the treatment of injuries with a deficit of less than 30 mm to bridge, the use of synthetic nerve conduits (NGC) is favored. However, to develop such promising therapeutic strategies, in vitro models that more faithfully mimic nerve physiology are needed. The absence of a clinically scaled model with essential elements such as a three-dimension environment and dynamic coculture has hindered progress in this field. The presented research focuses on the development of an in vitro coculture model of the peripheral nervous system (PNS) involving the use of functional biomaterial which microstructure replicates nerve topography. Initially, the behavior of neuron-derived cell lines (N) and Schwann cells (SC) in contact with a short section of biomaterial (5 mm) was studied. Subsequent investigations, using fluorescent markers and survival assays, demonstrated the synergistic effects of coculture. These optimized parameters were then applied to longer biomaterials (30 mm), equivalent to clinically used NGC. The results obtained demonstrated the possibility of maintaining an extended coculture of SC and N over a 7-day period on a clinically scaled biomaterial, observing some functionality. In the long term, the knowledge gained from this work will contribute to a better understanding of the PNS regeneration process and promote the development of future therapeutic approaches while reducing reliance on animal experimentation. This model can be used for drug screening and adapted for personalized medicine trials. Ultimately, this work fills a critical gap in current research, providing a transformative approach to study and advance treatments for PNS injuries.
摘要：
对外周神经系统(PNI)的创伤性损伤可导致严重的后果,例如瘫痪。不幸的是,目前的治疗很少允许令人满意的功能恢复。与PNS伤害相关的高医疗费用，工人残疾,和低患者满意度按替代解决方案，超越现行标准。对于桥梁缺损小于30毫米的损伤的治疗，使用合成神经导管（NGC）是有利的。然而,为了开发这种有前途的治疗策略，需要更忠实地模拟神经生理学的体外模型。缺乏具有诸如三维环境和动态共培养的基本要素的临床缩放模型阻碍了该领域的进展。本研究的重点是周围神经系统（PNS）的体外共培养模型的开发，该模型涉及使用功能性生物材料，该材料的微观结构可复制神经形貌。最初，研究了与一小段生物材料（5mm）接触的神经元衍生细胞系（N）和雪旺氏细胞（SC）的行为。随后的调查，使用荧光标记和存活测定，证明了共培养的协同效应。然后将这些优化的参数应用于更长的生物材料（30毫米），相当于临床使用的NGC。获得的结果表明，在临床缩放的生物材料上，可以在7天的时间内维持SC和N的延长共培养。观察一些功能。从长远来看,从这项工作中获得的知识将有助于更好地了解PNS再生过程，并促进未来治疗方法的发展，同时减少对动物实验的依赖。该模型可用于药物筛选并适用于个性化医学试验。最终,这项工作填补了当前研究的关键空白，为研究和推进PNS损伤的治疗提供了一种变革性的方法。
