Near Infrared Light Activated Adhesives for Nerve Repair

摘要 创伤造成的神经损伤，包括战斗、事故、运动损伤和神经病，影响着超过350,000人 每年在美国的患者会导致感觉丧失、慢性疼痛，有时还会导致永久性残疾。 如果周围神经损伤，通常需要手术治疗，因为修复速度慢，而且 再生。神经修复一般包括直接贴近切断的神经以寻找小间隙和 植入同种异体合成移植物，以促进较大神经间隙的神经再生。缝合是 神经修复的临床标准，包括外科手术下最外层或神经外膜的贴合 显微镜。神经外膜缝合费时费力，需要高超的技巧，并可导致慢性 炎症、纤维化和不对称紧张。现有的胶水通常不会提供显著的额外好处 且力学性能较差，使用复杂。缩短了手术时间， 产生最小张力近似，防止疤痕形成是改进修复的关键 周围神经损伤的结果和成本。在这项研究中，我们将开发NEAR的新剂型 红外线可激活粘合剂(NILAA)，用于快速神经外膜封闭和随后的神经修复。一套 将产生NILAA生物材料，并对其流变性和力学性能进行表征。这个 NILAA生物材料对不同波长和功率的近红外光的响应将是 确定的和最佳的密封条件将使用数学模型与热相结合来确定 成像。证明体外封闭有效的NILAAs将被用于确定神经修复的有效性 大鼠坐骨神经损伤模型的建立。NILAAs将用作胶水，用于密封小缝隙，即横向切口和AS 用胶带或包裹固定大(1厘米)SD坐骨神经缺损处的合成再生管道 道利鼠。肌电(EMG)反应、生物力学恢复、细胞和生化 将确定使用NILAA封闭和修复神经的反应，他们的表现将是 与缝合线和胶水相比。还将研究缝合NILAA的联合方法 促进神经修复。我们认为NILAAs是一种创新的神经外膜封闭、修复和修复方法。 再生大小神经缺损区可缩短手术时间，提高修复质量 包括低创伤、低疤痕和低炎症，这使得这项技术对临床非常有吸引力 翻译。

SUMMARY Nerve damage from trauma including combat, accidents, sports injuries, and neuropathies, affects over 350,000 patients annually in the U.S. resulting in loss of sensation, chronic pain, and sometimes permanent disability. Surgery is generally required for in case of peripheral nerve injury because of the slow rate of repair and regeneration. Nerve repair generally involves direct approximation of the severed nerves for small gaps and placement of allografts of synthetic grafts to facilitate nerve regeneration for large nerve gaps. Suturing is the clinical standard for nerve repair and involves apposition of the outermost layer or epineurium under a surgical microscope. Epineural suturing is time consuming, requires significant skill, and can result in chronic inflammation, fibrosis, and asymmetrical tension. Existing glues typically do not provide significant added benefit and suffer from weaker mechanical properties and complexities in application. Reduction in procedure times, generation of minimal-tension approximation, and prevention of scar formation are critical for improving repair outcomes and costs in peripheral nerve injuries. In this research, we will develop novel formulations of near infrared light activable adhesives (NILAAs) for rapid epineural sealing and subsequent nerve repair. A set of NILAA biomaterials will be generated and characterized for their rheological and mechanical properties. The response of NILAA biomaterials to different wavelengths and power intensities of near infrared light will be determined and optimal sealing conditions will be identified using a mathematical model in concert with thermal imaging. NILAAs that demonstrate effective ex vivo sealing will be used to determine efficacy of nerve repair in a sciatic injury model in rats. NILAAs will be used as glues to seal small gaps i.e. transverse incision and as tapes or wraps to secure synthetic regenerative conduits in large (1 cm) defects in the sciatic nerve in Sprague Dawley rats. Muscle electromyographic (EMG) response, biomechanical recovery, and cellular and biochemical responses will be determined for nerves sealed and repaired using NILAAs, and their performance will be compared to sutures and glues. A combination approach of sutures with NILAAs will also be investigated for facilitating nerve repair. We propose that NILAAs are innovative approach for epineural sealing, repair and regeneration of small as well as large nerve defects leading to faster operation times and better quality of repair including low trauma, scarring, and inflammation, which make this technology highly attractive for clinical translation.