On Demand Dissoluble Supramolecular Hydrogels: Towards Pain Free Burn Dressings

摘要 该提案描述了第一个的合成，表征和彻底评价 超分子杂化水凝胶烧伤敷料。我们的设计目标是a）按需溶解性-易于 无创伤地从烧伤伤口中去除，B）用于感染控制的综合抗微生物活性， 和c）自修复-用于无问题的应用和使用。烧伤是最常见的， 毁灭性的，需要紧急护理的问题。几乎每一分钟，美国都会有人 每天都有超过300名儿童到急诊室就诊，其中2人死亡 因为烧伤全球有数百万人患有烧伤相关的残疾， 对幸存者及其家人造成的情感和经济后果。去除烧伤敷料是 据报道，大多数疼痛的时间（烧伤本身之后），阿片类药物是主要的治疗方法， 痛苦重症监护室级别护理的典型损伤的烧伤敷料更换至少为57.6 分钟该过程的时间和复杂性随着频繁应用的麻醉而进一步增长。 重要的是，反复疼痛的敷料更换和伤口感染会导致更高的生命倾向- 可能导致败血症和多器官衰竭目前可用的烧伤敷料-临床使用-粘附 并通过外科手术或机械方法从伤口上清创。这导致 新上皮化组织的创伤、延迟愈合和剧烈疼痛。因此，我们建议 创建一个超分子杂化水凝胶结合主体-客体化学（葫芦脲[7]-主机 阳离子共聚物）与无机组分（即，粘土）（Aim 1）。这种水凝胶的独特特性将 由于其高生物相容性和通过金刚烷/二金刚烷按需溶解的能力 衍生物，容易和快速地去除和消除清创。这将减少极度疼痛， 痛苦（通过大幅减少疼痛的时间）。拟定的水凝胶还将嵌入 抗生素，以减少细菌感染。我们将通过体外（小鼠和人类）测试这种水凝胶 细胞，目的2）和体内（小鼠，目的3）和临床前（猪，目的3）实验。总的来说，我们的目标是 促进更好的烧伤伤口愈合，防止感染，并为患者提供无痛烧伤护理，符合 NIAMS的使命。该项目福尔斯再生医学（伤口愈合， 组织修复、再生）和大面积急性皮肤创伤（烧伤和创伤）的治疗 NIAMS 2020-2024财年战略计划中强调了这一点。该项目还侧重于a）改善 患者体验（减轻疼痛），和B）治疗烧伤伤口和感染的共发病症， NIAMS的两个重点领域。

Abstract This proposal describes the synthesis, characterization, and thorough evaluation of the first supramolecular hybrid hydrogel burn dressing. Our design goals are a) on-demand dissolubility -for easy trauma-free removal from burn wound-, b) integrated antimicrobial activity - for infection management-, and c) self-healing – for problem-free application and use. Burn injuries are one of the most prevalent, devastating, and demanding critical care problems, worldwide. Nearly every minute, someone in the US sustains a serious burn injury, and each day over 300 children visit emergency rooms and 2 of them die due to burn injuries. Millions, globally, suffer from burn-related disabilities with heavy psychological, emotional, and economic consequences on the survivors and their families. Burn dressing removal is reportedly the time of most pain (after the burn itself), and opioids are the primary treatment for such pain. The burn dressing change for a typical injury with intensive care unit level care is at least 57.6 minutes. The time and complexity of the process further grow with the frequently applied anesthesia. Importantly, repeated painful dressing changes and wound infection cause a higher predisposition to life- threatening sepsis and multi-organ failure. Currently available burn dressings – used clinically – adhere to the wound surface and are surgically or mechanically debrided from the wound. This results in the traumatization of newly epithelialized tissues, delayed healing and severe pain. We, thus, propose to create a supramolecular hybrid hydrogel combining the host-guest chemistry (cucurbituril [7]-hosted cationic copolymer) with inorganic components (i.e., clay) (Aim1). The unique feature of this hydrogel will be its high biocompatibility and ability to be dissolved on-demand via adamantane/diamantane derivatives, easily and quickly removed and eliminate debridement. This will reduce extreme pain and suffering (by drastically reducing time of pain). The proposed hydrogel will also be embedded with antibiotics to reduce bacterial infection. We will test this hydrogel through both in vitro (mouse and human cells, Aim 2) and in vivo (mouse, Aim 3) and preclinical (swine, Aim 3) experiments. Overall, our goal is to promote better burn wound healing, deter infection and provide pain-free burn care for patients, in line with the mission of NIAMS. This project falls under the umbrella of regenerative medicine (wound healing, tissue repair, regeneration) and treatment of large-area acute skin wounds (burns and trauma) highlighted in the NIAMS Strategic Plan for FY 2020-2024. The project also focuses on a) improving the patient experience (reducing pain), and b) treating co-occuring conditions of burn wounds and infections, two focus areas of NIAMS.