Objective evaluation of skin scarring pre- and post-therapy in human skin

Abstract

Wound healing is the process by which cutaneous damage is repaired, with the aim of restoring the production of tissue that is functionally and cosmetically similar to that of uninjured skin. There are three main outcomes that can occur following the initiation of the wound healing response which depend upon the type of tissue and the severity of the injury. These include tissue regeneration without a scar, repair of tissue with a scar or excessive scar tissue production. Skin scarring is a permanent end point of cutaneous injury in adult human skin. Effective therapies are lacking to combat these scars with many found to have limited efficacy and thus, treating them has remained a challenge. Thus, there is a need for objective monitoring of wound healing and scar formation as this is important for diagnosis, evaluation, prognosis, monitoring treatment response and can lead to the development of improved theranostic strategies, standardisation and validation of methodology for researchers. However, there is limited research that has used a number of these devices when assessing response to scar treatments and corroborated their findings with immunohistochemical analysis. Therefore, classification and definition of skin scarring using these objective quantitative devices could enable identification of novel therapeutic targets and biomarkers, standardise improved scar management approaches, predict response to therapies more effectively and translate into personalised treatments with improved outcomes. This thesis demonstrates the combined use of quantitative objective non-invasive devices and laboratory validation for the assessment of wound healing and skin scarring and has shown that this is an effective method of monitoring the progression of acute wound healing and enabling the identification of skin scar endotypes in order to optimise therapeutic response. Furthermore, five large clinical trials including two double-blind randomised controlled trials were conducted using electrical stimulation, photodynamic therapy and a novel topical therapeutic formulation for the treatment of skin scarring and treatment response was assessed using a multitiered approach using multiple quantitative non-invasive device measurements and laboratory gene and protein analyses used to validate findings. In summary, criteria has been proposed for defining scar endotypes and from this four distinct scar endotypes have been suggested (Stretched (flat), Contracted, Atrophic (depressed), Raised) each with specific clinical features and response to treatment. This thesis has demonstrated that the combined use of quantitative objective non-invasive devices and laboratory validation is an effective method of monitoring the progression of acute wound healing and skin scarring, measuring treatment response and enabling the identification of skin scar endotypes in order to optimise therapeutic response.

Date of Award	1 Aug 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Ardeshir Bayat (Supervisor)