Near Infrared Light Activated Adhesives for Nerve Repair

用于神经修复的近红外光激活粘合剂

• 批准号: 10436799
• 负责人: Kaushal Rege
• 金额: $ 19.72万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-23 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10436799
• 关键词: Accidents; Adhesions; Adhesives; Affect; Allografting; Anastomosis - action; Athletic Injuries; Biochemical; Biocompatible Materials; Biological Markers; Biomechanics; Chitosan; Chronic; Cicatrix; Clinical; Connective Tissue; Consumption; Defect; Development; Dyes; Enzyme-Linked Immunosorbent Assay; Evaluation; FDA approved; Fibrin Tissue Adhesive; Fibroins; Fibrosis; Formulation; Gelatin; Generations; Glues; Goals; Hand; Histopathology; Hour; Image; Immunofluorescence Immunologic; Immunohistochemistry; Indocyanine Green; Inflammation; Injury; Interleukin-1 beta; Interleukin-10; Lasers; Light; Mechanics; Mediating; Microscope; Modeling; Muscle; Natural regeneration; Near-infrared optical imaging; Nerve; Nerve Regeneration; Nerve Tissue; Neuropathy; Numbness; Operative Surgical Procedures; Outcome; PECAM1 gene; Pain; Patients; Performance; Peripheral Nerves; Peripheral nerve injury; Prevention; Procedures; Property; Rattus; Recovery; Repeat Surgery; Research; Rupture; Secure; Silk; Site; Skin repair; Sprague-Dawley Rats; Surgeon; Surgical incisions; Surgical sutures; TNF gene; Technology; Temperature; Tensile Strength; Testing; Time; Tissues; Trauma; caprolactone; cell motility; chronic pain; clinical translation; combat; cost; crosslink; cytotoxicity; disability; improved; indexing; innovation; insight; mathematical model; mechanical properties; nerve damage; nerve gap; nerve injury; nerve repair; novel; operation; poly(lactic acid); regenerative; repaired; response; sciatic nerve; seal; sealant; skills; soft tissue

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.

概括 创伤受到的神经损害，包括战斗，事故，运动损伤和神经病，影响超过350,000 美国每年在美国每年导致感觉丧失，慢性疼痛以及有时永久性残疾。 由于修复速度缓慢和 再生。神经修复通常涉及直接近似切断的神经，以解决小间隙和 合成移植物的同种异体移植物的放置，以促进大神经间隙的神经再生。缝合是 神经修复的临床标准，并涉及手术下最外层或epineurium的临床标准 显微镜。骨膜缝合是耗时的，需要大量技巧，并且可能导致慢性 炎症，纤维化和不对称张力。现有胶水通常不会提供巨大的额外好处 并遭受较弱的机械性能和应用中的复杂性。减少程序时间， 产生最小的张力近似和预防疤痕形成对于改善修复至关重要 周围神经损伤的结果和成本。在这项研究中，我们将开发新的 红外光活化粘合剂（NILAAS），用于快速的上皮密封和随后的神经修复。一组 NILAA生物材料将以其流变和机械性能产生和特征。这 NILAA生物材料对近红外光的不同波长和功率强度的反应将是 确定和最佳的密封条件将使用与热的数学模型一起确定 成像。证明有效的离体密封的尼拉斯将用于确定神经修复的功效 大鼠坐骨神经损伤模型。尼拉斯将用作密封小间隙的胶水，即横向切口和 胶带或包裹以在Sprague的坐骨神经中固定综合再生辅助 道利老鼠。肌肉肌电图（EMG）反应，生物力学恢复以及细胞和生化 将确定使用Nilaas密封和修复神经的响应，其性能将是 与缝合线和胶水相比。缝合线与尼拉斯的组合方法也将被研究 促进神经修复。我们建议Nilaas是胸膜密封，维修和的创新方法 小神经和大神经缺陷的再生，导致工作时间更快，维修质量更高 包括低创伤，疤痕和炎症，这使得这项技术对临床高度吸引力 翻译。