**1. Introduction**

Chronic venous ulceration is a common disease. Its prevalence is 1% of the total population, with 20% of venous ulcers presented in octogenarians [1–5]. Refractory venous leg ulceration is a common basis of morbidity [6, 7] and leads to a reduced quality of life [8], especially in the elderly population [4, 5]. It causes a considerable amount of work incapacity, social exclusion and lack of self‐esteem [4]. There is a probable underestimation of the true extent of venous leg ulceration in the general population due to its underreporting [7]. Venous ulcers are characterised by a recurring pattern of healing and subsequent 70% recurrence rate at one year [9–14]. Venous ulceration places a huge monetary burden on the healthcare system [15]. The cost of managing venous ulcers accrues to £400 million sterling per year in the UK [16].

Ambulatory venous hypertension is one of the leading causes of chronic reperfusion injury. This in turn provokes venous ulceration with its habitual history of chronicity and recurrence [1]. Over the past 40 years, compression bandaging has been the gold standard form of therapy for treatment of venous ulceration. We have learned that compression will both improve perfusion and enhance healing [2, 17, 18]. Nevertheless, active healthy tissue granulation can take upwards to 3 weeks to cultivate [19]. There‐ fore, the following question is posed: How can we speed up epithelial coverage in a granulating wound?

### **1.1. Topical wound oxygen**

Topical wound oxygen (TWO2) proposes an innovative therapy option in the management of refractory non‐healing venous ulcers (RVU) that aims to accelerate wound healing. The application of positive pressure oxygen to manage open wounds has been studied extensively and has demonstrated promising clinical results [20–28]. The systemic complications associ‐ ated with the use of a full‐body hyperbaric chamber have been overcome by the application of topical wound pure oxygen at an appropriate cycled pressure to only the specific wound site. This maximizes the beneficial wound healing effects and minimizes the negative systemic side effects [29].

Delivered through a targeted delivery system, a Hyper‐Box, TWO2 accelerates epithelial‐ isation and eliminates MRSA within 72 h. This leads to the development of a higher tensile strength collagen, which lessens scarring and the risk of recurrence [29–32]. Hyperbaric oxygen promotes angiogenesis and increases the expression of angiogenesis‐ related growth factors [33, 34]. It promotes leukocyte function with enhanced bactericidal activity [35–40]. The intermittent cycled pressure, under which TWO2 is delivered, stimulates circulation, reduces oedema and provides a sealed humidified environment essential for healing [41].
