Hyperbaric oxygen therapy (HBOT)
Oxygen plays an important role in the wound healing process. While tissue hypoxia labels the initial phase of wound healing and signals for angiogenesis and growth factors, a wound that is chronically depleted from oxygen will have impaired healing (Kranke et al. 2015). HBOT is a systematic oxygen supplementation in which a patient is sealed within a chamber filled with 100% oxygen at a pressure greater than sea level atmospheric pressure (Jirangkul et al. 2021). As HBOT raises the oxygen’s concentration in blood, more oxygen will reach the wound that has a higher metabolic demand (E. Huang, Heyboer, and Savaser 2019). The availability of oxygen will induce the synthesis of Nitric Oxide, promoting angiogenesis and increase the production of energy needed for tissue growth, cell recruitment, re-epithelization, and immune defense against bacteria (de Smet et al. 2017). Generally, HBOT is a lengthy therapy associated with few adverse events, including oxygen toxicity, anxiety and barotrauma such as rupture of ear membrane (Health Quality Ontario 2017). According to de Smet et al. (2017), HBOT results in faster wound closure and improved vascular perfusion. Specifically with skin grafts in carefully selected patients, HBOT is associated with better graft survival and less infection. The use of HBOT in the treatment of stalled but healable DFUs has shown to reduce frequency of surgical procedures and minimize the risk and extent of amputations (E. Huang, Heyboer, and Savaser 2019; Jirangkul et al. 2021). Additionally, Health Quality Ontario (2017) stated that HBOT may provide lower costs and better outcomes when compared to standard wound therapies. Nevertheless, additional studies are needed to properly select patients who are most likely to benefit from HBOT (E. Huang, Heyboer, and Savaser 2019). There is also a considerable cost that may not be covered by many health care systems except in cases with specialized criteria.
Electrical stimulation (ES)
Electrical Stimulation is considered an adjunctive treatment modality for chronic wound healing due to its effects on cutaneous perfusion, cell proliferation and migration, and bacterial growth (Thakral et al. 2013). It involves placing electrodes directly to the wound bed that delivers electrical charges that mimic the physiological electrical potentials proven to accelerate wound healing (Rajendran et al. 2021). Clinician training and experience within their scope of practice is a factor for consideration. ES is painless and safe to use; however, it is contraindicated in pregnancy and patients with osteomyelitis, cancer, skin conditions, blood clots or implanted electronic devices (Ontario Health Technology Advisory Committee 2017; Rajendran et al. 2021). According to Khouri et al. (2017), ES is shown to be more effective on pressure injuries than DFUs and VLUs with better outcomes linked to smaller wounds. Although ES has been found to significantly reduce wound surface area in chronic wounds compared to standard wound care, the evidence is uncertain for routine clinical use. This is due to variation in wound types, patient characteristics, ES parameters, and standard wound care evaluated across the studies (Ontario Health Technology Advisory Committee 2017; Rajendran et al. 2021).
Low-frequency US (20-40 kHz) is one of the most recent treatment methods used for debridement, bactericidal effect and healing of chronic wounds (Alkahtani et al. 2017; Kavros et al. 2008). As opposed to high-frequency US, that triggers mechanical and thermal effects reaching deep tissue layers, low-frequency US only creates a mechanical pressure wave reflected in the wound surface (Yadollahpour, Jalilifar, and Rashidi 2014). These mechanical effects include
- surface cavitation: generating and dissipating microbubbles in tissue
- acoustic streaming: movement of fluids across membranes
Both of these effects increase cellular activity as well as vascular permeability (Voigt et al. 2011).
Mechanical stimulation can also activate the Rac1 protein in fibroblasts, accelerating wound healing (Lyu et al. 2021). Low-frequency US can be delivered directly to the wound, known as high-intensity contact US, or indirectly via saline or water, known as low-intensity noncontact US (Voigt et al. 2011). Despite the low quality of evidence, low-frequency US has demonstrated better healing and smaller wound size for VLUs and DFUs. In comparison to sharp debridement, US was found to be relatively painless (Ruby Chang, Perry, and Cross 2017; Voigt et al. 2011). Lyu et al. (2021) proposed designing flexible US patches that can conform better to the wound surface for effect wound treatment. Larger, well-designed and well-conducted trials are needed to evaluate dose-response efficacy of US in different types of wounds before conclusions can be drawn (Jalilifar, Yadollahpour, and Rashidi 2015).