Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation

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.