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.

Project Narrative The project aims to develop light triggerable materials for improving the patients’ experience. The light- responsive polymer-local anesthetic conjugates designed in this project will enable pain relief controllable by the patient or clinician using a light source (light-emitting diode or laser). The photo-dissolvable polymeric adhesives designed in this project will provide a kind of tissue adhesives that not only can be firmly bonded to tissues but also can be easily and non-invasively removed by external triggering.