Exploring protease expression as a potential prognostic factor for wound healing

  • Joe Harvey

Student thesis: Phd


Background: Open wounds healing by secondary intention, such as venous leg and foot ulcers, can often exhibit delayed healing times making them costly to treat and manage for health services. The mechanisms of delayed healing have not been fully elucidated but are suspected to be multifactorial with multiple wound healing pathways affected. Various proteases have key roles in the wound healing process and many of these have been investigated as potential prognostic biomarkers for wound healing. Identified prognostic biomarkers could be used to estimate wound healing times, identify at risk wounds, or be modified directly as therapeutic targets. Although protease prognostic biomarker studies have previously been carried out many are limited by small sample sizes and study periods and high risk of bias. An additional challenge is the lack of infrastructure in place for translational research in community-based clinics, where most of these hard-to-heal wound types are treated. Large robust cohort studies are therefore required to improve wound healing prognostic biomarker research. Hypothesis and aims: Individual protease expression was hypothesised to be associated with wound healing times and so these proteins may be useful as prognostic biomarkers. The overarching aim of this thesis was therefore to identify and overcome translational issues in wound healing prognosis research to facilitate development of a large prospective cohort study for prognostic biomarker identification.’ Research approaches and findings: Many different methods are used to collect wound fluid for the investigation of protein expression and abundance. A scoping review was carried out to summarise and map the methods previously used and identify potential gaps in the literature. A suitable method type was identified which utilised extraction of wound fluid from patient dressings, but modifications were required before clinical use. A method was developed which was relatively noninvasive and simple while being moderately high throughput for use in larger studies. Material-analyte interactions for different dressing materials were tested using several target proteins in the developed method, with no differential absorption of specific proteins observed. The method was also validated via consistent measurement of protein abundance changes between target proteins in wound fluid compared to blister fluid controls. To assess feasibility of a large prognostic factor research study a pilot was conducted. The pilot study involved recruitment of 13 out of a possible 18 venous leg ulcer patients from a single community clinic. The primary issue identified in the pilot was a relatively high rate of attrition with no means of follow-up after participants had left the clinic. Several potential prognostic biomarkers were also highlighted for further study after measuring correlations of protein abundance with relative wound area. Research implications: The development of a validated wound fluid collection method and results from the clinical pilot will facilitate design and development of larger robust studies for wound healing prognostic biomarker research. Issues identified by the pilot will be resolved and the infrastructure and processes put in place will be expanded upon to enable these larger studies to take place.
Date of Award1 Aug 2024
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorRachel Watson (Supervisor) & Jo Dumville (Supervisor)


  • Proteomics
  • Matrix metalloproteinases
  • Biomarkers
  • Wound healing
  • Translational research
  • Venous leg ulcer
  • Prognosis research

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