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 350,000 人 在美国，每年都有患者因这种疾病而导致感觉丧失、慢性疼痛，有时甚至是永久性残疾。 由于周围神经损伤修复速度慢，一般需要手术治疗。 再生。神经修复通常涉及直接接近被切断的神经以获得小间隙和 放置合成移植物的同种异体移植物，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，涉及最外层或神经外膜在手术下的并置 显微镜。神经外缝合非常耗时，需要很高的技能，并且可能导致慢性损伤 炎症、纤维化和不对称张力。现有的胶水通常无法提供显着的附加优势 机械性能较差，应用复杂。减少手术时间， 产生最小张力近似值和防止疤痕形成对于改善修复至关重要 周围神经损伤的结果和费用。在这项研究中，我们将开发近 红外光激活粘合剂 (NILAAs) 用于快速神经外膜密封和随后的神经修复。一套 NILAA 生物材料将被生成并表征其流变学和机械性能。这 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 确定的最佳密封条件将使用与热相结合的数学模型来确定 成像。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 将用作胶水来密封小间隙，即横向切口，并用作 在斯普拉格的坐骨神经大（1厘米）缺损处使用胶带或包裹物固定合成再生导管 道利鼠。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 密封和修复的神经的反应，其表现将是 与缝合线和胶水相比。还将研究缝合与 NILAA 的组合方法 促进神经修复。我们认为 NILAA 是神经外膜密封、修复和治疗的创新方法 小型和大型神经缺损的再生，从而缩短手术时间并提高修复质量 包括低创伤、疤痕和炎症，这使得该技术对临床极具吸引力 翻译。