Extended Release of Bioactive Factors to Treat Refractory Wounds

延长释放生物活性因子来治疗难治性伤口

基本信息

批准号：
9924291
负责人：
Yadong Wang
金额：
$ 37.77万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-22 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9924291
关键词：
Abnormal Cell Anatomy Animal Model Antibiotics Area Becaplermin Blood Vessels Caregivers Caring Cell Proliferation Cell secretion Cells Chronic Cicatrix Clinical Collagen Complex Consumption DTR gene Debridement Deposition Dermal Diabetes Mellitus Diabetic Foot Ulcer Discipline of Nursing Dorsal Dose Emulsions Engineering Environment Epidermal Growth Factor Epidermal Growth Factor Receptor Epithelial Epithelial Cell Proliferation Epithelium Excision Excretory function Exhibits Family suidae Fascia Fibroblasts Foundations Frequencies Goals Granulation Tissue Growth Factor Health Health Care Costs Healthcare Heparin Heparin Binding Human In Vitro Individual Inflammation Infusion procedures Interruption Lead Literature Lower Extremity Measures Metabolism Modeling Morbidity - disease rate Mus Muscle Non-Insulin-Dependent Diabetes Mellitus Outcome Outcome Measure Oxidative Stress Patients Phenotype Physiological Play Process Property Protein Analysis Proteins Protocols documentation Quality of life Receptor Down-Regulation Refractory Research Role Safety Science Self Management Signal Transduction Site Skin Skin wound healing Streptozocin Structure of beta Cell of islet System Tensile Strength Testing Thick Time Treatment Cost Treatment Efficacy Treatment outcome Type 2 diabetic Wound models absorption angiogenesis base cell killing cell motility chronic wound clinically relevant cost design diabetic diabetic patient diabetic wound healing disability dosage efficacy testing healing improved infection risk innovation insight keratinocyte limb amputation mouse model new technology novel strategies open wound pressure productivity loss prototype response self reliance side effect skin wound stem cells success tissue repair translational study wound wound care wound closure wound healing

项目摘要

Extended release of bioactive factors to treat refractory wounds Chronic wounds significantly decrease quality of life, lead to severe disability, and are huge burdens on healthcare and caregivers. Diabetes mellitus is expected to afflict 366 million people worldwide by 2030. Among these patients, approximately 15% will develop diabetic foot ulcers. Underlying chronic wounds, abnormal cell phenotypes and chronic inflammation inhibit normal healing processes and elevate the risk of infection. Current clinical solutions are expensive, time-consuming, largely unsuccessful, and lack patient self-management. The overarching goal of this translational study is to advance nursing science and the wound care field, by healing chronic wounds with one-time administration of sustained, local release of growth factors. This effective and economical treatment will be achieved using a new vehicle that protects the bioactivity of the protein cargo. Growth factor signaling plays a pivotal role in the natural wound healing process. The major limitation in growth factor therapies has been the lack of an appropriate delivery system to provide for prolonged signaling. Controlled delivery of growth factor will reduce patient morbidity and risk of infection in chronic wounds while helping patients to manage their care more autonomously. This research focuses on testing the efficacy of a delivery system we recently designed for wound-implicated growth factors and has three specific aims: Aim 1. Investigate the effects of HB-EGF coacervate on wound healing in vitro using normal and diabetic primary human dermal cells and evaluate the safety of the coacervate treatment. Aim 2. Evaluate the efficacy of controlled delivery of HB-EGF to improve diabetic wound healing in a polygenic type 2 diabetic mouse model. Aim 3. Investigate the controlled delivery of HB-EGF to accelerate diabetic wound healing in a porcine model. This proposal will provide the foundation for an easy-to-use product that significantly improve healing of wounds, increase patient self-reliance and quality of life, and reduce the interruption and loss of productivity patients currently must accept. Therefore, this new technology would enable not only improved health outcomes, but also more self-management for individuals with chronic wounds.

延长释放生物活性因子来治疗难治性伤口慢性伤口显着降低生活质量，导致严重残疾，并且给医疗保健和护理人员带来巨大负担。预计将有 3.66 亿人罹患糖尿病到 2030 年，全世界范围内的患者中，大约 15% 将患上糖尿病足溃疡。潜在的慢性伤口、异常细胞表型和慢性炎症抑制正常的愈合过程并增加感染的风险。目前的临床解决方案是昂贵、耗时、基本上不成功，并且缺乏患者的自我管理。这这项转化研究的总体目标是推进护理科学和伤口护理通过一次性施用持续的局部生长释放来治愈慢性伤口因素。这种有效且经济的治疗将通过使用一种新的车辆来实现，该车辆可以保护蛋白质货物的生物活性。生长因子信号传导在自然伤口愈合过程中发挥着关键作用。这生长因子疗法的主要限制是缺乏适当的递送系统提供长时间的信号传递。生长因子的控制输送将降低患者发病率和慢性伤口感染的风险，同时帮助患者更好地管理他们的护理自主地。这项研究的重点是测试我们最近的输送系统的功效专为伤口相关的生长因子而设计，具有三个具体目标：目标 1. 使用正常和正常伤口体外研究 HB-EGF 凝聚层对伤口愈合的影响。糖尿病原代人真皮细胞并评估凝聚治疗的安全性。目标 2. 评估 HB-EGF 控制递送对改善糖尿病伤口愈合的功效在多基因2型糖尿病小鼠模型中。目标 3. 研究 HB-EGF 的控制递送以加速糖尿病伤口愈合猪模型。该提案将为易于使用的产品奠定基础，该产品将显着改善伤口愈合，提高患者的自力更生能力和生活质量，并减少目前患者必须接受中断和生产力丧失。因此，这项新技术不仅可以改善健康结果，还可以增强个人的自我管理能力有慢性伤口。