Bio-instructive' materials for chronic wound healing

在这个项目中，我们假设，具有促进快速上皮化、抑制炎症和增强血管形成能力的新型生物指导材料可以提供现有最先进的慢性伤口护理(例如聚氨基甲酸酯薄膜或水胶体)的替代方案。这些新的生物指导材料将用于开发下一代敷料和支架，用于糖尿病伤口和其他类型的慢性伤口和大面积烧伤的伤口护理的细胞疗法。在我们老龄化的人口中，有大量的患者患有慢性无法愈合的伤口。慢性伤口对患者和国家卫生服务来说是一个巨大的负担，仅在英国，估计每年的费用就达31亿英镑，占卫生预算总额的3%。在皮肤中，伤口愈合过程涉及不同类型的细胞之间的密切合作，包括上皮细胞、间质细胞(如成纤维细胞)、内皮细胞和免疫细胞特有的巨噬细胞。在正常情况下，皮肤上皮具有较高的更新能力，这是由于存在常驻干细胞，良好的灌注性，以及吞噬细胞有效地清除受损细胞，为再上皮化提供了最佳的环境。快速上皮化和伤口闭合恢复皮肤屏障功能，这是阻止感染的关键。然而，在深度损伤(例如大面积烧伤)或慢性不可愈合伤口的情况下，由于血管形成受损或慢性炎症(例如糖尿病)，上皮无法自我愈合的情况就达到了极限。这会造成无法愈合的伤口，容易造成慢性感染，造成慢性炎症循环和进一步的组织损伤。慢性不可愈合伤口的一个主要例子是糖尿病溃疡，其中高血糖水平、巨噬细胞功能受损、循环不良和慢性炎症使传统治疗无效，并使伤口护理成为临床挑战。

In this project we hypothesise that novel 'bio-instructive' materials with the ability to prompt fast re-epithelisation, hamper inflammation and enhance vascularisation could provide an alternative to the existing state-of-the-art in chronic wound care (e.g. polyurethane films or Hydrocolloids)). These novel bio-instructive materials will be used for developing next generation dressings and scaffolds for cell based therapies for wound care in diabetic wounds and other types of chronic wound and extensive burns. There are a large number of patients who suffer from chronic non-healing wounds in our ageing population. Chronic wounds represent a significant burden to patients and to the National Health Service, with an estimated cost of £3.1billion per year in the UK alone accounting for >3% of the total health budget. The problem is exacerbated by the increasing incidence of other conditions such as diabetes, vascular disease and long-term immobility.In the skin, the wound healing process involves close collaboration between different cell types including epithelial cell, stromal cells (e.g. fibroblast), endothelial cells and immune cells particularity macrophages. Under normal conditions skin epithelium has a high renewal capacity due to the presence of resident stem cells, good perfusion and efficient removal of damaged cells by phagocytic cells, providing an optimal environment for re-epithelization. Fast re-epithelisation and wound closure reinstate skin barrier function which is crucial for stopping infection. However, in the case of deep injuries (e.g. extensive burns), or chronic non-healing wounds, due to compromised vascularisation or chronic inflammation (e.g. in diabetes), a limit is reached where the epithelium self-healing cannot occur. This leads to creation of a non-healing wound that is prone to chronic infection creating a cycle of chronic inflammation and further tissue damage. A prime example of chronic non-healing wounds are diabetic ulcers where high glucose levels, compromised function of macrophages, poor circulation and chronic inflammation render conventional treatments non-efficient and make wound care a clinical challenge.