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

用于按需局部麻醉和组织粘合剂溶解的光触发材料

• 批准号: 10368292
• 负责人: Wei Zhang
• 金额: $ 10万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368292
• 关键词: Absence of pain sensation; Acute Pain; Adhesions; Adhesives; Anesthesia procedures; Award; Binding; Biocompatible Materials; Biodistribution; Cessation of life; Chemicals; Chemistry; Cicatrix; Constipation; Crosslinker; Development; Devices; Drug Delivery Systems; Drug Kinetics; Economic Burden; Encapsulated; Excision; Formulation; Glues; Goals; Hematoxylin and Eosin Staining Method; Histologic; Immunomodulators; In Vitro; Inflammation; Lasers; Light; Local Anesthetics; Local anesthesia; Medical; Mentors; Modeling; Nausea; Nerve; Nerve Block; Operative Surgical Procedures; Opioid; Opioid Analgesics; Pain; Pain management; Particulate; Patients; Pattern; Pharmaceutical Preparations; Phase; Polymers; Positioning Attribute; Prevention; Property; Pruritus; Quality of life; Rattus; Reaction; Science; Series; Social Problems; Source; Stains; Steroids; System; Testing; Tetrazolium; Therapeutic; Time; Tissue Adhesives; Tissues; Training; Treatment Efficacy; Work; addiction; adhesive polymer; base; biomaterial compatibility; career; career development; chemical binding; chemical bond; chemical conjugate; chronic pain; crosslink; design; efficacy study; experience; functional group; improved; in vivo; in vivo imaging; innovation; interest; irradiation; mechanical properties; novel; overdose death; pain relief; physical property; prevent; response; safety study; sciatic nerve; side effect; skills; wound healing

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.

项目摘要 有效控制急性和慢性疼痛是与患者生活质量有关的主要医学挑战。 使用全身药物治疗通常与问题有关，例如成瘾，非法滥用 甚至死亡，导致社会问题和经济负担。局部麻醉是有效的替代方案 在治疗局部疼痛的情况下而不会蒙上灰度，并且全身副作用通常很少见。 在指导的K99阶段，PI将设计，合成和表征新颖的光响应性 聚合物 - 本地麻醉偶联物可用于按需局部疼痛治疗。在此设计中，局部麻醉药 只能通过光触发才能逆转的方式在化学上与聚合物载体结合。 该项目中开发的材料将实现局部麻醉释放系统，在该系统首先之后 给药，缓解疼痛的缓解将由患者或临床使用光源实时控制（光 发射二极管或激光）。当与PI的化学和聚合物科学背景相结合时， 在物质阶段进行培训和结果将使PI在R00阶段赋予能力，以进一步扩展 光触发材料在设计，合成和表征的新型光响应性中的应用 组织粘合剂。大多数现有的组织粘合剂在应用过程中对重新定位不便，去除 不需要的住所，或在错误的位置纠正胶水的无意位置。 R00项目将开发 组织粘合剂基于具有光透明特性的可交联的多型聚合物。材料会 在光照射下可以溶解，从而使粘合剂方便且无创的去除。期间 奖项期，PI将在体内接受药物输送系统，轻响应材料的培训 材料的特征和职业发展培训，这将大大增加PI的广度 在生物材料方面的技能经验，并为他的独立学术生涯做好准备。