Development of optoelectronically active nerve adhesive for accelerating peripheral nerve repair

项目概要 周围神经（PN）损伤是一个重大的公共卫生问题，会导致功能障碍和 永久性残疾。显微外科缝合是长间隙 PN 修复的标准方法，但非常耗时 手术并导致神经损伤、炎症性异物反应和疤痕形成，从而延迟 PN 再生。作为潜在的替代品，组织粘合剂已被开发出来以减少手术时间 并避免二次损坏。然而，目前市售的组织粘合剂，如纤维蛋白胶和 其他的，考虑到细胞毒性、广泛肿胀导致的组织压缩以及较差的效果，远非理想。 机械性能。我们开发了一种新型双网络神经粘合剂（NA），由儿茶酚组成 改性透明质酸和脱细胞周围神经基质水凝胶。我们的 NA 显着说明了 与仅儿茶酚修饰的 HA 和商业纤维蛋白相比，具有更高的粘附强度和粘附力 胶水。与相比，NA 支持雪旺细胞增殖并改善横切损伤后的 PN 修复 为纤维蛋白胶。然而，微缝合后感觉和运动功能仍未完全恢复 或 NA 修复横切和长间隙神经损伤模型。在本提案中，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 损伤再生的光电活性 NA (optoENAs)。硅基μ太阳能电池处于 微米尺寸、生物相容性、可生物降解和可光刺激以产生足够的电力输出。 研究的具体目标是 (1) 开发功能性 optoENA 并确定其大小和大小如何 μ-太阳能电池的浓度影响NA特性和PN相关的细胞行为； (2) 确定是否 以及 optoENAs 如何加快手术过程、促进自体移植物植入并促进长间隙 PN 在大鼠模型中进行修复。该提案将开发一种新型且临床适用的组织粘合剂，具有增强的 粘合性能和光电性能可改善长间隙 PN 的愈合和再生 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.