Development of optoelectronically active nerve adhesive for accelerating peripheral nerve repair

项目摘要 周围神经（PN）损伤代表了一个主要的公共卫生问题，导致功能障碍， 终身残疾。显微外科手术是长间隙PN修复的标准方法， 手术并导致神经损伤、炎症性异物反应和瘢痕形成， PN再生作为潜在的替代品，组织粘合剂已被开发用于减少手术时间 避免二次伤害。然而，目前市售的组织粘合剂，如纤维蛋白胶和纤维蛋白胶， 其他的，考虑到细胞毒性、由于广泛肿胀引起的组织压缩和不良的 力学性能我们开发了一种新型的双网络神经粘合剂（NA）， 改性透明质酸和脱细胞外周神经基质水凝胶。我们的NAs显著地说明了 与仅邻苯二酚修饰的HA和商业纤维蛋白相比，具有更高的粘附强度和粘附力 胶与对照组相比，NAs支持雪旺细胞增殖并改善横断损伤后PN修复。 纤维蛋白胶然而，显微手术后感觉和运动功能仍未完全恢复 或NA修复。在本建议中，我们将进一步纳入 创新的光电生物材料（即，Si基μ太阳能电池），以开发下一代 光电活性NA（optoENA）用于长间隙PN损伤再生。Si基μ太阳能电池在 微米尺寸、生物相容性、生物可降解性和光刺激性以产生足够的电输出。 这些研究的具体目的是（1）开发功能性optoENA，并确定其大小和 μ-太阳能电池的浓度影响NA性质和PN相关的电池行为;以及（2）确定是否 以及optoENA如何加快外科手术、促进自体移植物植入和促进长间隙PN 在大鼠模型中修复。该提案将开发一种新型的和临床上可应用的组织粘合剂， 用于改善长带隙PN的愈合和再生的粘合性能和光电性能 损伤

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.