Hydrogels for treating chronic wounds: a multi-pronged approach

水凝胶治疗慢性伤口：多管齐下

基本信息

批准号：
10458596
负责人：
Naphtali Andre O'Connor
金额：
$ 11.08万
依托单位：
HERBERT H. LEHMAN COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10458596
关键词：
Antioxidants Attention Binding Biology Blood Circulation Cancer cell line Cell Proliferation Characteristics Chemicals Chemistry Chronic Collaborations Curcumin Cystine Development Dextrans Diabetes Mellitus Diabetic Foot Ulcer Effectiveness Engineering Enzymes Equilibrium Esters Evaluation Extracellular Matrix Proteins Exudate Fibroblasts Foot Ulcer Hemostatic function Hydrogels Impaired wound healing In Vitro Infection Inflammation Inflammatory Kinetics Leg Ulcer Link Matrix Metalloproteinase Inhibitor Matrix Metalloproteinases Melatonin Metals Methods Peptide Hydrolases Peptides Polymers Process Production Property Reporting Ribose Silver Source Systemic disease Therapeutic Universities Varicose Ulcer Vascular Diseases Vascular Endothelial Growth Factors Venous Water Zinc absorption antimicrobial antimicrobial dressing bisphosphonate chelation chronic wound college cost crosslink design diabetic experience healing improved in vitro activity keratinocyte microbial nanoparticle porcine model success therapeutic target wound dressing wound healing

项目摘要

Project Summary/Abstract Chronic leg and foot ulcers are considerably slow healing, lasting on average 12 to 13 months. They are commonly associated with systemic diseases and conditions with impaired wound healing such as diabetes and vascular disease. For example, diabetic leg ulcers are an example of a difficult to heal chronic wound associated with diabetes and venous leg ulcers are a chronic wound attributed to poor blood circulation. A hallmark of these chronic wounds is out of balance inflammation caused by elevated levels of proteases, reactive oxidative species (ROS) and instances of infection. Herein is proposed the design and evaluation of hydrogels that target multiple aspects of a toxic inflammatory process. These hydrogels are designed to counteract the high levels of ROS, proteolytic activity and microbial infection present in chronic wounds. Hydrogels comprised of polydopamine and curcumin will be developed to impart antioxidant activity. Various strategies will be examined to counteract proteolytic matrix metalloproteinase (MMP) activity. Zn2+ is responsible for the catalytic activity of MMP and binding the metal is a well-established method to reduce its proteolytic activity. Curcumin is an antioxidant with zinc chelation ability that has been shown to reduce MMP activity and improve wound healing. We will synthesize water-soluble degradable curcumin polymers for incorporation within hydrogels. We propose these curcumin hydrogels will lower ROS and MMP activity. Polydopamine will be used to synthesize silver nanoparticles (AgNPs) within the hydrogels. AgNPs are well known for their antimicrobial properties but have also been demonstrated to inhibit MMP. A third strategy is to chemically modify hydrogels with bisphosphonate MMP inhibitors. On the other hand, agents that promote cell proliferation are also shown to accelerate the healing process. We will examine the effect of releasing 2-deoxy-D-ribose and melatonin, compounds shown to promote proliferative processes while the hydrogel concurrently suppresses inflammation. Keywords. Hydrogels, chronic wounds, antimicrobial, wound healing, matrix metalloproteinase

项目概要/摘要慢性腿部和足部溃疡的愈合速度相当缓慢，平均持续 12 年至 13 个月。它们通常与全身性疾病有关伤口愈合受损的情况，例如糖尿病和血管疾病。例如，糖尿病性腿部溃疡就是难以治愈的慢性溃疡的一个例子。与糖尿病和腿部静脉溃疡相关的伤口是一种慢性伤口归因于血液循环不良。这些慢性伤口的一个特点是平衡蛋白酶、反应性氧化水平升高引起的炎症物种（ROS）和感染实例。在此提出设计方案并评估针对有毒炎症多个方面的水凝胶过程。这些水凝胶旨在抵消高水平的活性氧，慢性伤口中存在蛋白水解活性和微生物感染。水凝胶将开发由聚多巴胺和姜黄素组成的抗氧化剂活动。将研究各种策略来抵消蛋白水解基质金属蛋白酶（MMP）活性。 Zn2+负责催化活性 MMP 和金属结合是减少其蛋白水解的行之有效的方法活动。姜黄素是一种具有锌螯合能力的抗氧化剂，已被经证明可降低 MMP 活性并改善伤口愈合。我们将综合用于掺入水凝胶中的水溶性可降解姜黄素聚合物。我们建议这些姜黄素水凝胶会降低 ROS 和 MMP 活性。聚多巴胺将用于合成银纳米颗粒（AgNP）水凝胶。 AgNP 以其抗菌特性而闻名，但也已被证明具有抑制 MMP 的作用。第三种策略是化学修饰具有双膦酸盐 MMP 抑制剂的水凝胶。另一方面，代理商促进细胞增殖也被证明可以加速愈合过程。我们将检查释放 2-脱氧-D-核糖和褪黑激素化合物的效果显示出促进增殖过程，而水凝胶同时抑制炎症。关键词。水凝胶，慢性伤口，抗菌，伤口愈合，基质金属蛋白酶