Bioactive nerve guides - anti-inflammatory and anti-scarring devices

在欧盟，每年有超过30万例外周神经因外伤或手术而受损。与中枢神经系统不同，近端运动轴突和感觉轴突具有一定的修复能力。对于没有组织损伤的个体，可以直接将近端和远端缝合在一起，作为端端吻合术。在设计修复方法时，对损伤的分子和细胞反应的基本理解是必不可少的，特别是对于植入式神经引导导管（NGCs）。我们已经详细回顾了NGC的性能1，结论支持生物材料改善NGC是一种现实的方法（例如与细胞治疗相比）。NGCs通常由惰性生物材料（如聚酯、胶原蛋白）制成，不会刺激神经细胞或雪旺细胞粘附、迁移或分化以修复神经。因此，现有设备在支持再生方面很差。一个主要的挑战是将再生距离从几毫米增加到10-20毫米的临界间隙距离。为了临床实践的改进，本项目提出了生物材料化学的简单创新，并结合制造反映神经力学特性的多孔和柔性材料的制造方法。在这个项目中，我们还将解决与神经修复相关的炎症和疤痕问题。因此，设备将提供关键的抗炎药（a-MSH, IL-10）和/或抗疤痕化合物（M6P），已知可改善功能修复。本博士项目将在体外和体内对设备进行评估，并进行舌神经重建的临床研究。

Injury to peripheral nerves through trauma, and sometimes surgery, results in over 300,000 cases each year in the EU. In contrast to the central nervous system, proximal motor and sensory axons have some ability to repair. Individuals who sustain injury with no loss of tissue can be treated by directly suturing proximal and distal ends together, as end-end anastomosis. A fundamental understanding of the molecular and cellular responses to injury is essential when designing approaches for repair, especially for implantable nerve guide conduits (NGCs). We have reviewed NGC performance in detail1, with conclusions supporting biomaterials improvements in NGCs a realistic approach (e.g. versus cell therapy). NGCs are typically made from inert biomaterials (e.g. polyesters, collagen), and do not stimulate neuronal or Schwann cell adhesion, migration or differentiation for nerve repair. Consequently, existing devices are poor at supporting regeneration. A major challenge is to increase regeneration distance from a few millimetres to critical gap distances of 10-20 mm. For clinically practical improvement, simple innovations in the biomaterial chemistry, in combination with fabrication methods for making porous and flexible materials to reflect the mechanical properties of nerve are proposed and will be investigated in this project. In this project we also will address the problems of inflammation and scarring associated with nerve repair. Devices will therefore delivery key anti-inflammatories (a-MSH, IL-10) and/or an anti-scarring compound (M6P) known to improve functional repair. Devices will be evaluated in vitro, and in vivo in this PhD project, with a route to following on a clinical study of lingual nerve reconstruction.