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

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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.