Development of optoelectronically active nerve adhesive for accelerating peripheral nerve repair

项目摘要 周围神经(PN)损伤是一个主要的公共卫生问题，导致功能障碍和 永久残疾。作为修复长间隙PN的标准方法，显微外科缝合是一项耗时的工作 程序和导致神经损伤，炎性异物反应和疤痕形成，这将延迟 PN再生。作为潜在的替代品，组织粘合剂已经被开发出来以减少手术时间 避免二次伤害。然而，目前商业上可用的组织粘合剂，如纤维蛋白胶和 其他的，远不理想，考虑到细胞毒性，由于广泛的肿胀而导致的组织压缩，以及较差 机械性能。我们研制了一种由邻苯二酚组成的新型双网络神经粘合剂(NA) 改性透明质酸和脱细胞周围神经基质水凝胶。我们的Nas很好地说明了 与邻苯二酚修饰的HA和商业纤维蛋白相比，具有更高的粘接强度和粘附力 胶水。NAS支持雪旺细胞增殖和促进横断损伤后PN修复的比较 纤维蛋白粘合剂。然而，显微缝合后感觉和运动功能仍未完全恢复。 或在横断和长间隙神经损伤模型中进行NA修复。在这项建议中，我们将进一步纳入 NA内的创新光电生物材料(即硅基μ太阳能电池)，以开发下一代 用于长间隙PN损伤再生的光电子活性NAs。硅基μ太阳电池在 微米大小，生物相容，可生物降解，光刺激，可产生足够的电力输出。 这些研究的具体目标是：(1)开发功能性视神经诱发电位，并确定其大小和 μ太阳能电池的浓度影响NA特性和PN相关的电池行为；以及(2)确定 以及光学ENAs如何加快手术过程，促进自体移植，并促进长间隙PN 在大鼠模型中修复。这项建议将开发一种新型的临床适用的组织粘合剂，具有增强的 用于改善长间隙PN愈合和再生的粘接性能和光电性能 受伤。

Project Summary Peripheral nerve (PN) injury represents a major public health problem that leads to functional impairment and permanent disability. Microsurgical suturing, standard approach for long-gap PN repair, is a time-consuming procedure and causes nerve damage, inflammatory foreign body reactions, and scar formation, which delay the PN regeneration. As potential alternatives, tissue adhesives have been developed to reduce operation time and avoid secondary damages. However, current commercially available tissue adhesives, like fibrin glue and others, are far from ideal, considering cytotoxicity, tissue compression due to extensive swelling, and poor mechanical properties. We have developed a novel dual network nerve adhesive (NA) consisting of catechol modified hyaluronic acid and decellularized peripheral nerve matrix hydrogels. Our NAs illustrated significantly higher adhesion strength and adhesion force, compared to catechol modified HA only and commercial fibrin glue. The NAs supported Schwann cell proliferation and improved PN repair after transection injury comparing to fibrin glue. However, both sensory and motor functions were still incompletely recovered after microsuturing or NA repair in the transected and long-gap nerve injury models. In this proposal, we will further incorporate innovative optoelectronic biomaterials (i.e., Si based μ-solar cells) within the NA to develop next generation of optoelectronically active NAs (optoENAs) for long-gap PN injury regeneration. The Si based μ-solar cells are in micrometer size, biocompatible, biodegradable, and photo-stimulable to generate sufficient electrical output. The specific aims of the studies are (1) to develop functional optoENA and determine how the size and concentration of μ-solar cells affect NA properties and PN related cell behaviors; and (2) to determine whether and how optoENAs expedite surgical procedures, facilitate autograft implantation, and promote long-gap PN repair in a rat model. This proposal will develop a novel and clinically applicable tissue adhesive with enhanced adhesive performance and optoelectronic properties for improving healing and regeneration of long-gap PN injury.