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

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.

There are numerous beneficiaries of this Advanced Biomedical Materials CDT. Firstly and of short term impact are the PhD students themselves. They will receive extensive research specific and professional/transferable skills training throughout the 4 years of the programme. They will have access to state of the art facilties and world leading academics, industry and clinicians. The training and potential placements are designed to maximise the impact of their research in terms of dissemination and movement of their research along the translation pathway.

Longer term benefits are that this distinct cohort will become the future UK Biomedical Materials leaders and be able to use their bespoke training and network within the cohort to collaborate on future worldwide funding opportunities and drive UK research in this area.

UK and international academics will benefit as they will gain the next generation of highly skilled postdoctoral researchers with knowledge and expertise not only in their specific research area but of industry, regulatory and clinical aspects.

UK and international industry will benefit - in the short term they will gain academic based research to further develop products and in the longer term have a pool of highly skilled graduates.

Clinicians will benefit from collaborative research and also the development of new and novel products to enhance the treatment of a variety of trauma and disease based needs from biomaterials.

The public will benefit as end users as patients that will have their quality of life improved from the products developed in the CDT and will be educated in novel technologies and materials to repair the human body. The UK economy will benefit from the reduced healthcare costs associated with the new and improved medical products developed in this CDT and subsequently from the trained graduates. The UK economy will also benefit from the increased revenue from medical sales products from the UK industrial partners we will be working with.

The impact of this CDT will be realised by direct academic, clinical and industrial engagement with the students allowing efficient and state of the at training and fast translation of developing products. Students will also be trained in knowledge exchange and will use these skills to disseminate their research to, and liaise with, the key stakeholders - the academic, industrial, clinical and public sectors. We will ensure widening participation routes are addressed in this CDT in order to include equality and diversity not only in our initial CDT student cohort but in future researcher generations to come.