Bio-instructive' materials for chronic wound healing

在这个项目中，我们假设新的“生物指导”材料能够促进快速再上皮，阻碍炎症和增强血管化，可以为慢性伤口护理提供现有最先进的替代方案（例如聚氨酯薄膜或水胶体）。这些新型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细胞治疗。在我国老龄化人口中，有大量患者患有慢性无法愈合的伤口。慢性伤口对患者和国民健康服务来说是一个重大负担，仅在英国，每年的费用估计为31亿英镑，占卫生总预算的3%。糖尿病、血管疾病和长期不活动等其他疾病的发病率不断增加，加剧了这一问题。在皮肤中，伤口愈合过程涉及不同类型细胞之间的密切合作，包括上皮细胞、基质细胞（如成纤维细胞）、内皮细胞和免疫细胞（特别是巨噬细胞）。在正常情况下，由于存在常驻干细胞，良好的灌注和吞噬细胞对受损细胞的有效清除，皮肤上皮具有很高的更新能力，为再上皮化提供了最佳环境。快速再上皮和伤口愈合恢复皮肤屏障功能，这是至关重要的停止感染。然而，在深度损伤（如大面积烧伤）或慢性不愈合伤口的情况下，由于血管受损或慢性炎症（如糖尿病），达到了上皮不能自我愈合的极限。这导致伤口无法愈合，容易产生慢性感染，形成慢性炎症和进一步组织损伤的循环。慢性不愈合伤口的一个主要例子是糖尿病性溃疡，其中高血糖水平、巨噬细胞功能受损、血液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.