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.

软组织疤痕造成的功能缺陷是全球巨大的医疗负担。伤口不仅与皮肤损伤有关，而且还与影响所有软组织的创伤区域有关，通过筋膜互连导致重要结构周围的纤维化。临床上观察到的表现为疼痛、僵硬和活动能力丧失。此外，糖尿病和肥胖等疾病会导致更大的组织功能障碍，从而使这一过程变得更加复杂。世界上高达 1-2% 的人口一生中至少遭受过一次慢性损伤后遗症。在英格兰，国家医疗服务体系 (NHS) 每年必须承担约 15.3 亿英镑的损伤恢复费用。人体组织由结缔组织束缚，结缔组织的行为就像无摩擦且相当无定形的凝胶。这些筋膜组织由嵌入称为细胞外基质 (ECM) 的纤维状和凝胶状环境中的各种细胞组成。这种 ECM 会发生巨大变化，尤其是在受伤、衰老和某些疾病期间。有趣的是，细胞产生并同时响应基质变化。在健康条件下，ECM 保持稳态，但在疾病条件下，ECM 合成和分解可能会失去平衡，从而导致 ECM 硬化和纤维化（基质产生过多），进而导致受影响组织的功能障碍。该项目旨在了解筋膜基质疤痕的分子机制、机械力对其的影响以及生物材料如何模拟致病基质的合成和机制，最终有助于识别新的治疗方法。