Novel therapeutic targets for diabetes-related wounds or ulcers: an update on preclinical and clinical research

ABSTRACT

Introduction

Diabetes-related wounds, particularly diabetes-related foot ulcers, are mainly caused by lack of foot sensation and high plantar tissue stress secondary to peripheral neuropathy, ischemia secondary to peripheral artery disease, and dysfunctional wound healing. Current management of diabetes-related wounds involves the offloading of high foot pressures and the treatment of ischemia through revascularization. Despite these treatments, the global burden of diabetes-related wounds is growing, and thus, novel therapies are needed. The normal wound healing process is a coordinated remodeling process orchestrated by fibroblasts, endothelial cells, phagocytes, and platelets, controlled by an array of growth factors. In diabetes-related wounds, these coordinated processes are dysfunctional. The past animal model and human research suggest that prolonged wound inflammation, failure to adequately correct ischemia, and impaired wound maturation are key therapeutic targets to improve diabetes-related wound healing.

Areas covered

This review summarizes recent preclinical and clinical research on novel diabetes-related wound treatments. Animal models of diabetes-related wounds and recent studies testing novel therapeutic agents in these models are described. Findings from clinical trials are also discussed. Finally, challenges to identifying and implementing novel therapies are described.

Expert opinion

Given the growing volume of promising drug therapies currently under investigation, it is expected within the next decade, that diabetes-related wound treatment will be transformed.

KEYWORDS:

• Diabetes-related foot ulcers
• wounds
• diabetic complications
• treatment
• therapeutic targets
• clinical trials
• animal models

Article highlights

• The main causes of diabetes-related wounds are high plantar tissue stress due to peripheral neuropathy, ischemia due to peripheral artery disease, and dysfunctional wound healing.

• Despite the current available treatments, the global burden of diabetes-related wounds is growing.

• Chronic inflammation, resistant ischemia, and impaired wound maturation are key treatment targets to improve diabetes-related wound outcomes.

• Clinically relevant animal models need to be used in testing of novel therapies.

• Larger clinical trials are required to confirm the promising results from the current smaller trials testing novel therapies.

This box summarizes key points contained in the article.

Declaration of Interests

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Disclosure statement

Peer reviewers in this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This research was supported by grants from the National Health and Medical Research Council (1180736), Townsville Hospital and Health Service Study, Education and Research Trust Fund, James Cook University, and Queensland Government. JG holds a Practitioner Fellowship from the National Health and Medical Research Council (1117601) and a Senior Clinical Research Fellowship from the Queensland Government.