Preventing Chronic Fibrosis Using Smart Implantable Hydrogels

: (Alternative Format Thesis)

Abstract

Fibrosis represents up to 45% of all deaths in the Western Hemisphere. Failed wound resolution and impaired immune cell clearance are the key features of chronic fibrosis, leading to perpetual cycles of extracellular matrix deposition, inflammation, and progressive tissue damage. While pharmacological interventions have shown utility in certain fibrotic diseases (cystic fibrosis and idiopathic pulmonary fibrosis), they often act on broad biological pathways. These treatments are not localised to the fibrotic region, resulting in off-target non-specific effects that limit their therapeutic potential, especially for soft tissue wounds. Biomaterial approaches offer an alternative, used to directly target wound sites, before the development of fibrosis, to direct cell behaviour via both a physical scaffold and biocompatible cues to promote effective wound resolution and immune clearance. Matrikines are short peptide sequences derived from the proteolytic cleavage of extracellular matrix proteins such as collagen, fibrinogen, and decorin. Functioning as cytokine-like molecules, these peptides can influence cellular proliferation and differentiation, act as cytokine agonists, and interact with cell surface receptors such as integrins to regulate adhesion. This body of work focuses on the development of five short anti-fibrotic matrikine peptides that are appended in situ onto the α-helical hydrogelating self-assembling fibres (hSAF) hydrogel via copper-catalysed azide alkyne cycloaddition (CuAAC). Early optimisation and exploratory studies encompassed peptide synthesis, material characterisation, and novel CuAAC approaches. These were followed by an in vitro assessment of fibrotic responses in murine 3T3 fibroblasts to evaluate the anti-fibrotic potential of each matrikine sequence.

Date of Award	24 Jun 2026
Original language	English
Awarding Institution	University of Bath
Supervisor	Jody Mason (Supervisor) & Nazia Mehrban (Supervisor)