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