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Title: The variation of integrin-β1, FAK, ERK on post-burn hypertrophic scars : an implication for pressure therapy
Authors: Zhang, Yuting
Degree: M.Phil.
Issue Date: 2019
Abstract: Hypertrophic scar (HTS) is an abnormal yet common complication of severe burns. One key component that affects HTS the formation of HTS during wound healing is mechanical force, which can be converted into chemical signals and thereby later cell proliferation, migration and adhesion. The mechanisms of force-regulating cell behaviors via interactions between mechanosensitive molecules and intracellular signaling like integrin­ß1, focal adhesion kinase (FAK) and extracellular (ERK) are known as mechanotransduction. Pressure therapy is a frontline treatment for HTS in which compression force is used to intervene in the scarring process. However, controversy persists among specialists due to its ambiguous mechanism. To date, attempts have been made to explain pressure therapy from a mechanotransduction perspective. Unlike the abundant evidence regarding the interaction between mechanotransduction and stretch-induced scarring during early wound healing, few studies have explored the involvement of mechanotransduction on growing or matured HTS under compression. Therefore, the aim of the phase I study was to find the relationship between post injury days and the immunoreactivity of integrin-ß1, FAK and ERK on human HTS to establish a reference of mechanosensitive molecules on growing or matured HTS. The aim of phase II study was to compare the immunoreactivity of integrin-ß1, FAK and ERK on human HTS before and after pressure therapy as a preliminarily exploration of the effect of pressure therapy on mechanotransduction. Finally, the clinical effect of pressure therapy on convex area considering the compression from three dimensions is reported in the phase III study in an attempt to optimize the clinical application of pressure therapy. This thesis begins with an overview of the epidemiology and pathophysiology of HTS and a review of mechanotransduction in fibrosis, with a focus on predominant molecules in force-regulating scarring such as integrin-ß1, FAK and ERK. The history and mechanisms of pressure therapy are then introduced. To assist with the design of the main study, the confounding factors of pressure therapy were summarized in a systematic review.
In phase I of the study, an observational study was conducted to explore the relationship between post injury days and the immunoreactivity of integrin-ß1, FAK and ERK on human HTS; 31 subjects with 43 HTS specimens were obtained. An increase in the immunoreactivity of integrin-ß1, FAK and ERK was revealed between 2 and 3 months after injury, suggesting a critical time for intervention using external force such as pressure therapy. A pretest-posttest study was designed in phase II to explore the effects of pressure therapy on mechanotransduction. Forty-three HTS specimens were obtained before and after pressure therapy. The immunoreactivity of dermal integrin-ß1, FAK and ERK was found to decrease after pressure therapy, and an earlier treatment showed a greater benefit. The study preliminarily demonstrated an effect of pressure therapy in the down-regulation of mechanosensitive molecules in the dermis. Based on findings of the phase II study, and the high expression of FAK detected by other researchers over the perilesional region of aggressive scars, phase III of the study describes a case report in which modified pressure therapy generated compression force on convex hypertrophic scars from three dimensions (3D) was described. The objective scar thickness was found to be controlled after the application of 3D pressure therapy. This case report shows a translation from the preclinical findings to effective clinical practice. In conclusion, the immunoreactivity of integrin-ß1, FAK, and ERK was found to be elevated between 2 and 3 months after injury, and an earlier application of pressure therapy could contribute to the down-regulation of dermal integrin-ß1 and FAK expression. From a clincial aspect, the application of adequate compression on areas in which greater activation of mechanosensitive molecules was found, can control the progression of scarring. Further research is needed for a deeper comprehension of the signalling pathway of compression force on HTS in humans.
Subjects: Hong Kong Polytechnic University -- Dissertations
Hypertrophic scars -- Care
Pressure -- Therapeutuc use
Pages: xviii,108 pages : color illustrations
Appears in Collections:Thesis

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