A multidisciplinary approach to model and reveal the mechanisms of fibrotic tissue formation follow injury"

软组织疤痕造成的功能缺陷是世界范围内巨大的医疗负担。创面不仅与皮肤损伤有关，而且是一个影响所有软组织的创伤性区域，通过筋膜相互连接导致重要结构周围的纤维化。在临床上，这表现为疼痛、僵硬和行动不便。此外，糖尿病和肥胖等疾病使这一过程变得复杂，这些疾病会导致更大的组织功能障碍。多达1%-2%的世界人口在一生中至少遭受一次伤害的慢性后遗症。在英格兰，国民健康服务(NHS)每年必须支付约15.3亿英镑的损伤恢复费用。身体组织由结缔组织结合，其行为就像无摩擦和相当无定形的凝胶。这些筋膜组织由各种细胞组成，这些细胞嵌入在称为细胞外基质(ECM)的纤维和胶状环境中。这种细胞外基质会发生巨大的变化，特别是在受伤、衰老和某些疾病期间。有趣的是，细胞产生并同时对基质的变化做出反应。在健康条件下，ECM保持动态平衡，但在疾病条件下，ECM的合成和分解可能会失去平衡，从而导致ECM僵硬和纤维化(过度产生基质)，这反过来可能导致受影响组织的功能障碍。本项目旨在了解筋膜基质瘢痕形成的分子机制，机械力如何影响这一机制，生物材料如何模拟致病基质合成，以及最终有助于识别新治疗方法的机制。

Functional deficits from soft tissue scarring represent an enormous worldwide healthcare burden. Wounds are not only associated with skin injuries but also a zone of trauma that affects all the soft tissues resulting in fibrosis around vital structures through fascial interconnections. Clinically this is observed as pain, stiffness, and loss of mobility. Furthermore this process is complicated by diseases such as diabetes and obesity that lead to greater tissue dysfunction. Up to 1-2% of the world population is suffering from the chronic sequalae of injury at least once during a lifetime. In England, the National Health Service (NHS) must cover costs of around £1.53 billion on injury recovery annually.The body's tissues are bound by connective tissues that behave like frictionless and fairly amorphous gels. These fascial tissues consist of a variety of cells that are embedded in a fibrous and gelatinous environment called the extracellular matrix (ECM). This ECM alters enormously particularly during injury, ageing, and certain diseases. Intriguingly, cells produce, and simultaneously respond to matrix changes. Under healthy conditions the ECM is kept in homeostasis but under disease conditions the ECM synthesis and disassembly can get out of balance thus causing stiffening of ECM and fibrosis (excess of matrix production), which in turn can lead to malfunctioning of the affected tissues. This project aims to understand the molecular mechanisms of fascial matrix scarring, how this is influenced by mechanical forces and how biomaterials can model pathogenic matrix synthesis and mechanisms that will ultimately aid identification of novel treatments.