The use of pulsed electromagnetic field to promote diabetic wound healing in different wound models

Abstract

Wound healing involves complex processes and people with diabetes mellitus (DM) often present with a delay in wound healing. Microvascular changes are common DM-related complications that may lead to foot oedema that is associated with a reduction in oxygen delivery to the tissues that results in foot ulceration. Pseudomonas aeruginosa (PAO1) is a common pathogen found in ulcers among people with DM. Photoacoustic measurement is an advanced technology that allows quantitative measurement of the oxyhemoglobin concentration on plantar skin or wound site in human or small animals. An effective treatment for infected DM ulcer may result in restoring normal oxyhemoglobin concentration, which can prevent lower limb amputation. Pulsed electromagnetic field (PEMF) is a potential non­invasive intervention that might be able to control inflammation, enhance tissue perfusion in wound area and promote healing of infected cutaneous wounds. In this thesis, we adopted several animal models to determine whether pulsed electromagnetic field (PEMF) would enhance healing of chronic wound model infected with PAO1. Therefore, this thesis consists of four inter-related studies. In terms of treatment, a systematic review was conducted to evaluate the effectiveness of biophysical energies in promoting wound healing in vivo and in vitro diabetic wound models. Then in Study I, we first examined the skin morphology and oxyhemoglobin concentration of plantar soft tissue in people with type 2 DM with or without neuropathy and ulceration. Study II examined the efficacy and underlying biological mechanism of PEMF on restoring oxyhemoglobin concentration and promoting acute dermal wounds healing in Streptozotocin-induced DM rat models. Since DM wound healing is a complex process that might be contributed by the underlying pathology or exogenous bacteria, we set off to study whether pulsed electromagnetic field would promote healing of infected wound with PAO1 in non-DM model. Subsequently, we examined the efficacy of PEMF in promoting dermal wounds healing with or without PAO1 in a chronic wound model in Study III. In the last part of this thesis (study IV), we further examined the efficacy of PEMF in promoting dermal wounds healing in acute and chronic wounds with or without PAO1 in a transgenic DM mice model. Chronic wound is a major complication of DM. A positive correlation between the subepidermal oedema and the oxyhemoglobin concentration was found at the heel region of people with DM. People with DM tend to develop subepidermal oedema as compared to their non-DM counterpart. However, epidermal thinning occurs in those people who have already developed DM complications and skin break down may lead to ulceration. Our animal studies demonstrated that PEMF was effective in promoting dermal wounds healing in a streptozotocin-induced DM rat in terms of oxyhemoglobin concentration and wound size, and in non-diabetic chronic wound model in terms of wound size. Moreover, histological analyses showed that PEMF might potentially enhance wound closure, angiogenesis and tissue remodeling in a DM chronic wound model. Yet, large scale clinical trials are warranted to translate the current findings into clinical practice.