Hydrogels for treating chronic wounds: a multi-pronged approach

项目摘要/摘要 慢性腿部和足部溃疡愈合相当缓慢，平均持续12天。 到13个月。它们通常与系统性疾病有关， 伤口愈合受损的情况，如糖尿病和血管疾病。 例如，糖尿病腿部溃疡是一种难以治愈的慢性疾病。 与糖尿病和静脉性小腿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征是 平衡由升高的蛋白水解酶、反应性氧化引起的炎症 物种(RO)和感染实例。在此提出了一种新的设计方案 针对毒性炎症多方面作用的水凝胶的评价 进程。这些水凝胶旨在中和高水平的ROS， 慢性创面存在蛋白分解活性和微生物感染。水凝胶 由多巴胺和姜黄素组成的抗氧化剂将被开发出来 活动。将研究各种策略来中和蛋白质分解基质 金属蛋白酶(MMPs)活性。锌离子对金属离子的催化活性起主要作用 MMPs与金属结合是一种公认的减少其蛋白质分解的方法 活动。姜黄素是一种具有锌螯合能力的抗氧化剂，已被 可降低基质金属蛋白酶活性，促进伤口愈合。我们将综合 用于水凝胶中的水溶性可降解姜黄素聚合物。 我们认为这些姜黄素水凝胶可以降低ROS和基质金属蛋白酶的活性。 聚多巴胺将用于合成银纳米颗粒(AgNPs) 水凝胶。AgNPs以其抗菌性能而闻名，但也有 已被证明能抑制基质金属蛋白酶。第三种策略是化学修饰 含有双膦酸类基质金属蛋白酶抑制剂的水凝胶。另一方面，那些 促进细胞增殖也被证明可以加速愈合过程。我们 将检测释放2-脱氧-D-核糖和褪黑素的效果，化合物 显示促进了增殖过程，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

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