Diabetes-related foot disease - Emerging treatments

Adjunctive therapies for diabetic foot ulcers

A wide range of adjunctive therapies are in development for the treatment of diabetic foot ulcers, some of which are already available in some healthcare systems.[79][80] The American Diabetes Association refers to these collectively as ‘advanced wound therapy’, of which there are nine broad categories: negative-pressure wound therapy (standard electrically powered and mechanically powered); oxygen therapies (hyperbaric oxygen therapy, topical oxygen therapy, oxygen-releasing sprays, and dressings); biophysical therapies (electrical stimulation, diathermy, pulsed electromagnetic fields, pulsed radiofrequency energy, low-frequency non-contact ultrasound, and extracorporeal shock wave therapy); growth factors (platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor); autologous blood products (platelet-rich plasma, whole blood clot, and leukocyte, platelet, and fibrin multilayered patches); acellular matrix tissues (xenograft dermis and xenograft acellular matrices, including placental-derived amniotic tissues, amniotic fluid, and umbilical cord); bioengineered allogeneic cellular therapies (bilayered skin equivalent such as human keratinocytes and fibroblasts, and dermal replacement therapy with human fibroblasts); stem cell therapies (autogenous bone marrow–derived stem cells, and allogeneic amniotic matrix with mesenchymal stem cells); and miscellaneous active dressings including hyaluronic acid, honey dressings, and sucrose octasulfate dressing.[37] The International Working Group on the Diabetic Foot (IWGDF) conducted a comprehensive literature review on adjunctive therapies as part of its 2023 guidelines update.[55] It concluded there is evidence to support the use of negative-pressure wound therapy for post-operative wounds, as well as topical and hyperbaric oxygen therapy, placental derived products and a leucocyte, fibrin, and platelet patch (the 3C Patch). See Management approach (Wound debridement) for discussion of negative-pressure wound therapy, and below for discussion of oxygen therapy, placental-derived products, and the 3C Patch. However, for all other adjunctive therapies, the IWGDF concluded there is currently insufficient evidence from clinical trials to support their use, and none are recommended at present.[55]

Topical and hyperbaric oxygen therapy

Hyperbaric oxygen therapy (breathing 100% oxygen at twice the atmospheric pressure of sea level) and topical oxygen therapy have both been found to improve healing of diabetic foot ulcers in some randomised controlled trials, albeit of low-quality evidence.[55][81][82][83] The IWGDF cautiously recommends their use as an adjunctive therapy where standard of care alone has failed, in places where the appropriate resources and equipment exist to provide them. In the UK, however, NHS England does not recommend use of hyperbaric oxygen based on current evidence.[84] Neither NHS England nor NICE currently makes any recommendations about the use of topical oxygen therapy. The cost effectiveness of hyperbaric oxygen therapy remains uncertain.[85]

Placental derived products

Numerous products have been derived from human placenta to assist with healing of diabetic foot ulcers, including dehydrated amnion/chorion graft, dehydrated amniotic membrane, cryopreserved placental membrane, and dehydrated umbilical cord. Several studies have suggested these can improve and speed up healing of ulcers, and they can be considered as an adjunctive treatment where standard of care alone has failed, according to the IWGDF. However, the quality of evidence is low and the cost effectiveness of these products remains unclear.[55]

3C Patch®

The 3C Patch® (previously known as LeucoPatch®) is a single-use medical device that is used as part of wound care for foot ulcers in people with diabetes. It uses a centrifuge device to create a biological patch from a person's own blood. The patch is a disc-shaped layered matrix of fibrin, leukocytes, and platelets and acts as a concentrated source of cells, growth factors, and signalling molecules, which are thought to promote wound healing. 3C Patch is under assessment for the management of recalcitrant wounds. Randomised controlled trial evidence suggests that using 3C Patch led to more ulcers healing at 20 weeks compared with standard care, and median time to ulcer healing of 72 days compared with 84 days in the standard care group.[86] The IWGDF supports its use as an adjunctive therapy where best standard of care alone has been ineffective, and where the resources and expertise exist for the regular venepuncture required.[55] The National Institute for Health and Care Excellence does not recommended the 3C patch as a cost-saving option for diabetic foot ulcers.[87]

Local/rotational soft-tissue flaps and skin grafting

Many advanced soft-tissue and/or bone reconstruction options have been described for patients with large foot wounds; however, they are not commonly used in clinical practice. The goal of these options is to achieve an intact skin surface in a functional, weight-bearing surface on the residual foot, thereby avoiding major (above-ankle) amputation. The outcomes of these procedures can be excellent. A theme throughout the studies is the agreement that diabetic foot wounds may be suitable for closure with local random flaps after infection has been addressed through surgical debridement and antibiotic therapy, after devitalised tissue has been removed, and when lower-extremity vascular status is intact.[88] Patients should be referred to an interdisciplinary diabetic foot clinic for evaluation for these procedures.