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

项目概要 有效控制急慢性疼痛是关系到患者生活质量的重大医学挑战。 全身药物治疗经常与问题相关，例如成瘾、非法滥用 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方案 治疗局部疼痛而不影响感觉中枢，全身副作用通常不常见。 在指导的 K99 阶段，PI 将设计、合成和表征新颖的光响应 用于按需局部疼痛治疗的聚合物-局部麻醉缀合物。在本设计中，局部麻醉剂 将以化学方式结合到聚合物载体上，这种方式只能通过光触发来逆转。 该项目开发的材料将实现局部麻醉释放系统，其中首先 给药时，疼痛缓解将由患者或临床医生使用光源（光- 发射二极管或激光器）。结合 PI 在化学和高分子科学方面的背景， 指导阶段的培训和结果将使 PI 在 R00 阶段能够进一步扩展 光触发材料在新型光响应材料的设计、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过程中不方便重新定位，去除 不需要的残留物，或纠正无意中将胶水放置在错误的位置。 R00项目将开发 基于具有光裂解特性的可交联多臂聚合物的组织粘合剂。该材料将 在光照射下可溶解，从而可以方便且非侵入性地去除粘合剂。期间 奖励期间，PI将接受药物输送系统、光响应材料、体内 材料的表征以及职业发展培训，这将大大增加 PI 的广度 生物材料方面的技能经验，并为他独立的学术生涯做好准备。

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.