Light triggered materials for on-demand local anesthesia and tissue adhesive dissolution

项目摘要 有效控制急性和慢性疼痛是与患者生活质量相关的主要医学挑战。 全身性药物治疗通常与成瘾、非法滥用等问题有关。 甚至死亡，导致社会问题和经济负担。局部麻醉剂是有效的替代品 在治疗局部疼痛而不使感觉模糊方面，全身副作用通常是罕见的。 在指导K99阶段，PI将设计，合成和表征新型光响应 用于按需局部疼痛治疗的聚合物-局部麻醉剂缀合物。在这种设计中，局部麻醉剂 将以只能通过光触发逆转的方式化学结合到聚合物载体上。 在这个项目中开发的材料将使局部麻醉剂释放系统，在第一次 在给药期间，疼痛缓解将可由患者或临床医生使用光源（光- 发光二极管或激光器）。结合PI在化学和聚合物科学方面的背景， 指导阶段的培训和结果将使PI在R 00阶段进一步扩展 光致变色材料在新型光响应材料设计、合成和表征中的应用 组织粘合剂。大多数现有的组织粘合剂在应用、移除和/或移除过程中不便于重新定位。 不希望的残留物，或纠正胶水在错误位置的无意放置。R 00项目将开发 基于具有光可裂解特性的可交联多臂聚合物的组织粘合剂。材料将 在光照射下可溶解，从而允许方便且非侵入性地去除粘合剂。期间 在授予期间，PI将接受药物输送系统，光响应材料，体内 材料的特性，以及职业发展培训，这将大大增加PI的广度 在生物材料的技能经验，并为他准备一个独立的学术生涯。

Project Summary Effective control of acute and chronic pain is a major medical challenge related to patients’ quality of life. Treatment with systemic medications is frequently associated with problems, such as addiction, illegal abuse and even death, leading to social problems and economic burden. Local anesthetics are effective alternatives in treating localized pain without clouding the sensorium, and systemic side effects are generally uncommon. During the mentored K99 phase, the PI will design, synthesize and characterize novel light-responsive polymer-local anesthetic conjugates for on-demand local pain treatment. In this design, the local anesthetics will be chemically bound to polymeric carriers in a manner that could only be reversed by photo-triggering. Materials developed in this project will enable a local anesthetic release system, in which after first administration, pain relief will be controllable in real-time by the patient or clinician using a light source (light- emitting diode or laser). When combined with the PI’s background in chemistry and polymer science, the training and results in the mentored phase will empower the PI, in the R00 phase, to further extend the application of light triggerable materials to the design, synthesis and characterization of novel light-responsive tissue adhesives. Most existing tissue adhesives are inconvenient to reposition during the application, remove undesired residue, or correct inadvertent placement of glue in the wrong position. The R00 project will develop tissue adhesive based on crosslinkable multiarmed polymers with photocleavable properties. The material will be dissolvable upon light irradiation, allowing convenient and non-invasive removal of the adhesives. During the award period, the PI will receive training in drug delivery systems, light-responsive materials, in vivo characterizations of materials, and training in career development, which will greatly increase the PI’s breadth of skills experience in biomaterials and prepare him for an independent academic career.