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

在欧盟，每年因创伤（有时是手术）造成的周围神经损伤超过30万例。与中枢神经系统相反，近端运动和感觉轴突具有一定的修复能力。没有组织损失的损伤个体可以通过直接将近端和远端缝合在一起来治疗，作为端-端吻合。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导管（NGC）。我们已经详细审查了NGC的性能1，结论支持NGC中的生物材料改进是一种现实的方法（例如，与细胞治疗相比）。NGC通常由惰性生物材料（例如聚酯、胶原蛋白）制成，并且不刺激神经元或许旺细胞粘附、迁移或分化用于神经修复。因此，现有的装置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。对于临床实践的改进，在生物材料化学中的简单创新，结合制造方法，用于制造多孔和柔性材料，以反映神经的机械性能，提出并将在本项目中进行研究。在这个项目中，我们还将解决与神经修复相关的炎症和瘢痕形成问题。因此，装置将递送已知改善功能修复的关键抗炎剂（a-MSH、IL-10）和/或抗瘢痕形成化合物（M6 P）。在本博士项目中，将对器械进行体外和体内评价，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.