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.

总结 创伤造成的神经损伤，包括战斗，事故，运动损伤和神经病，影响超过35万人。 在美国，每年都有患者出现感觉丧失、慢性疼痛，有时甚至是永久性残疾。 在周围神经损伤的情况下通常需要手术，因为修复速度慢， 再生神经修复通常涉及对于小间隙的切断神经的直接接近， 放置同种异体或合成移植物，以促进大神经缺损的神经再生。缝合是 神经修复的临床标准，并涉及在外科手术下最外层或神经外膜的并置 显微镜硬膜外麻醉是耗时的，需要大量的技能，并可能导致慢性 炎症纤维化和不对称张力现有的胶水通常不提供显著的附加益处 并且存在机械性能较弱和应用复杂的问题。缩短手术时间， 产生最小张力对合和防止瘢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，我们将开发新的配方近 用于快速神经外膜封闭和随后的神经修复的红外光活化粘合剂（NILAAs）。一组 将生成NILAA生物材料，并对其流变学和机械性能进行表征。的 NILAA生物材料对不同波长和功率强度的近红外光的响应将是 确定和最佳的密封条件将使用数学模型与热 显像证明有效的离体密封的NILAA将用于确定神经修复的功效， 大鼠坐骨神经损伤模型。NILAA将用作粘合剂密封小间隙，即横向切口， 在Sprague的坐骨神经中，用胶带或包裹物将合成再生导管固定在大的（1 cm）缺损中 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NILAA密封和修复神经的反应，并将确定其性能。 与缝合线和胶水相比。还将研究缝线与NILAA的组合方法， 促进神经修复。我们认为NILAAs是神经外膜封闭、修复和 再生的小以及大的神经缺损导致更快的手术时间和更好的修复质量 包括低创伤、疤痕和炎症，这使得该技术对临床具有高度吸引力。 翻译.