Complement in chronic wound infections: complementary or a cascade of chaos?

Chronic wounds are non-healing ulcers and are frequently accompanied with bacterial infection. These wounds bypass the normal healing process due to impaired cellular responses and excessive inflammation, likely triggered by bacterial infection and biofilm formation. Complement dysregulation, particularly the overproduction of anaphylatoxin C5a, is a pathogenic variable in many inflammatory diseases and other infectious diseases. There is some evidence that overproduction of C5a may contribute to poor healing outcomes; however, more research is required to clarify its role and determine how this influences host–pathogen interactions within the wound environment. Studying the complement system in a research environment is challenging due to factors such as sample composition, timing of collection, temperature and freeze–thaw cycles, all potentially affecting data reliability. Furthermore, various methods are available to study complement activity, including assays for bacterial opsonisation, serum bactericidal killing, and detection or quantification of individual complement components. This article explores the important role of complement dysregulation in chronic wound healing and discusses important considerations for advancing research in this area, including optimisation of laboratory processes to ensure accurate data.