On Demand Dissoluble Supramolecular Hydrogels: Towards Pain Free Burn Dressings

按需可溶性超分子水凝胶：迈向无痛烧伤敷料

基本信息

批准号：
10658220
负责人：
Ayse Asatekin
金额：
$ 48.72万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10658220
关键词：
Acceleration Acute Adamantane Adoption Adult Anesthesia procedures Animal Model Animals Antibiotics Area Bacterial Infections Biocompatible Materials Burn injury Caring Cells Cessation of life Chemicals Chemistry Child Clinic Clinical Critical Care Data Debridement Development Economics Electric Burns Electrostatics Emergency department visit Emotional Endothelial Cells Epithelium Evaluation Excision Exposure to Face Family Family suidae Fibroblasts Fire - disasters Foreign-Body Reaction Generations Goals Gram-Negative Bacteria Histology Hour Human Hybrids Hydrogel Bandage Hydrogels Immune Immune Tolerance Impaired healing In Vitro Inbred BALB C Mice Infection Infection prevention Inflammatory Inflammatory Response Injury Intensive Care Units Interleukin-6 Kinetics Length of Stay Life Lymphocyte Macrophage Mechanics Methods Mission Modeling Multiple Organ Failure Mus National Institute of Arthritis, and Musculoskeletal, and Skin Diseases Natural regeneration Operative Surgical Procedures Opioid Pain Pain Free Patient Care Patients Performance Persons Predisposition Procedures Process Property Regenerative Medicine Reporting Reproducibility Risk Sepsis Silver Skin Sodium Sterile coverings Strategic Planning Sulfadiazine Surface Survivors Swelling TNF gene Testing Time Tissues Toxic effect Trauma United States Water Wound Infection Wound models antimicrobial aqueous biomaterial compatibility burn wound clay clinically relevant copolymer cost crosslink cytokine design disability experience experimental study falls healing improved in vitro Model in vivo in vivo evaluation infection management keratinocyte mechanical properties nanosheet novel open wound pain reduction pediatric patients physical property polyacrylate pre-clinical psychologic rational design response second degree burn severe burns skin wound tissue repair wound wound healing

项目摘要

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.

抽象的该建议描述了第一个的综合，表征和彻底评估超分子混合水凝胶燃烧敷料。我们的设计目标是a）按需溶解性 - 简单从烧伤伤口中无创伤 - b）综合抗菌活性 - 用于感染管理 - c）自我修复 - 用于无问题的应用和使用。烧伤是最普遍的之一，全球毁灭性的和要求重症监护问题。几乎每一分钟，美国的人遭受严重的烧伤，每天有300多名儿童访问急诊室，其中2个死亡由于烧伤。全球数以百万计情感和经济后果对生存及其家人。烧伤敷料是据报道，大多数疼痛的时间（在烧伤本身之后），阿片类药物是这样的主要治疗方法疼痛。典型的重症监护仪护理典型伤害的燃烧调味料至少为57.6 分钟。该过程的时间和复杂性随着经常应用的麻醉而进一步增长。重要的是，反复的疼痛敷料变化和伤口感染会导致寿命更高 - 威胁败血症和多器官失败。目前可用的燃烧敷料 - 临床上使用 - 粘附到一眼，并通过手术或机械从伤口进行调试。这导致新上皮组织的创伤，延迟愈合和剧烈疼痛。因此，我们建议创建一种结合宿主 - 环化学的超分子杂化水凝胶（Cucurbituril [7] hosted 阳离子共聚物）与无机成分（即粘土）（AIM1）。该水凝胶的独特特征将是其高生物相容性和通过阿甘坦烷/二氨烷溶解的能力衍生品轻松快速地删除并消除调试。这将减轻极端疼痛和痛苦（通过大大减少疼痛时间）。提出的水凝胶也将与抗生素可减少细菌感染。我们将通过体外测试该水凝胶（小鼠和人类细胞，AIM 2）和体内（小鼠，AIM 3）和临床前（猪，AIM 3）实验。总的来说，我们的目标是为了促进更好的烧伤伤口愈合，确定感染并为患者提供无痛的烧伤护理带有尼亚姆斯的任务。该项目属于再生医学的伞（伤口愈合，组织修复，再生）和大区域急性皮肤伤口的治疗（烧伤和创伤）在2020 - 2024财年的NIAMS战略计划中强调。该项目还侧重于a）改进患者经历（减轻疼痛），b）治疗烧伤伤口和感染的共归因于 Niams的两个焦点区域。