Abstract
Delayed wound healing can cause significant issues for immobile and ageing individuals as well as those living with co-morbid conditions such as diabetes, cardiovascular disease, and cancer. These delays increase a patient’s risk for infection and, in severe cases, can result in the formation of chronic, non-healing ulcers (e.g., diabetic foot ulcers, surgical site infections, pressure ulcers and venous leg ulcers). Chronic wounds are very difficult and expensive to treat and there is an urgent need to develop more effective therapeutics that restore healing processes. Sustained innate immune activation and inflammation are common features observed across most chronic wound types. However, the factors driving this activation remain incompletely understood. Emerging evidence suggests that the composition and structure of the wound microbiome may play a central role in driving this dysregulated activation but the cellular and molecular mechanisms underlying these processes require further investigation. In this review, we will discuss the current literature on: 1) how bacterial populations and biofilms contribute to chronic wound formation, 2) the role of bacteria and biofilms in driving dysfunctional innate immune responses in chronic wounds, and 3) therapeutics currently available (or underdevelopment) that target bacteria-innate immune interactions to improve healing. We will also discuss potential issues in studying the complexity of immune-biofilm interactions in chronic wounds and explore future areas of investigation for the field.
Highlights
Wounds are a broad category of injuries that include everything from minor cuts and scrapes to surgical incisions and serious trauma
The innate immune system plays a critical role in modulating these processes as well as the transition from inflammation to proliferation phases, which includes a transition of inflammatory macrophages (M1) into anti-inflammatory wound healing cells (M2; Step 3) [86, 87]
Ageing and immobile individuals as well as those with co-morbid conditions such as diabetes are at high risk for developing nonhealing or chronic wounds
Summary
Wounds are a broad category of injuries that include everything from minor cuts and scrapes to surgical incisions and serious trauma. As the global population continues to age and experience increasing rates of co-morbid chronic diseases such as diabetes, there is an urgent need to understand the pathophysiology of delayed healing or the formation of non-healing wounds to develop more effective therapies that can repair tissue damage and restore health [3]. Chronic wounds show a considerable diversity in the bacterial species at the site of injury, but it is unclear how these differences contribute to chronicity These bacteria form robust biofilms, which embed the bacterial cells in a self-produced polymeric matrix, protecting them from host immune responses and antibiotics. In this review we will discuss the current understanding of how interactions between bacterial biofilms and innate immune cells drive damaging inflammatory processes that contribute to delayed healing in chronic wounds. We will discuss how we can target these interactions to develop novel therapeutics for individuals with difficult to treat chronic wounds
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