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

多学科方法建模并揭示损伤后纤维化组织形成的机制"

• 批准号: 2729099
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2729099
• 关键词: multidisciplinary; approach; model; reveal; mechanisms

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.

功能性定义的软组织疤痕代表了全球范围内巨大的医疗保健伯恩。伤口不仅与皮肤损伤有关，而且还与创伤区有关，该区域会影响所有软尖端，从而通过筋膜互连在重要结构周围产生纤维化。从临床上讲，这被认为是疼痛，僵硬和流动性丧失。此外，诸如糖尿病和肥胖症等疾病会导致更大的组织功能障碍，这一过程变得复杂。多达1-2％的世界人口在一生中至少遭受了慢性损伤的慢性半恋。在英格兰，国家卫生局（NHS）每年必须支付约15.3亿英镑的伤害恢复费用。人体的组织受到连接的组织的约束，这些组织的行为像无摩擦和相当无定的凝胶一样。这些筋膜组织由多种细胞组成，这些细胞嵌入了称为细胞外基质（ECM）的纤维和凝胶环境中。 ECM在受伤，衰老和某些疾病期间的积极变化。有趣的是，细胞会产生并容易响应基质变化。在健康的条件下，ECM保持体内平衡，但在疾病条件下，ECM合成和拆卸可能会失去平衡，从而导致ECM和纤维化僵硬（基质产生过量），这又会导致受影响组织的失功。该项目旨在了解筋膜矩阵疤痕的分子机制，这如何受到机械力的影响以及生物材料如何建模致病基质合成和机制，这些机制最终将有助于鉴定新的治疗方法。