The zone model: A conceptual model for understanding the microenvironment of chronic wound infection

In 2008, two articles in Wound Repair and Regeneration changed the clinical perspective on chronic wounds. They stated that chronic wounds that do not heal contain bacterial biofilms and that these biofilms may be one of the reasons for the nonhealing properties of the wounds. However, we still do not understand the exact role biofilms play in the halted healing process, and we are not able to successfully treat them. The reason for this could be that in vivo biofilms differ substantially from in vitro biofilms, and that most of the knowledge about biofilms originates from in vitro research. In this article, we introduce the zone model as a concept for understanding bacterial behavior and the impact of the microenvironment on both the host and the bacteria. Until now, identification of bacteria, gene expression, and postscript regulation have been looking at a bulk of bacteria and averaging the behavior of all the bacteria. As the zone model dictates that every single bacterium reacts to its own microenvironment, the model may facilitate the planning of future research with improved clinical relevance. The zone model integrates physiology and biology from single cells, microbial aggregates, local host response, surrounding tissue, and the systemic context of the whole host. Understanding the mechanisms behind the actions and reactions by a single bacterium when interacting with other neighboring bacteria cells, other microorganisms, and the host will help us overcome the detrimental effects of bacteria in chronic wounds. Furthermore, we propose use of the terminology "bacterial phenotype" when describing the actions and reactions of bacteria, and the term "biofilms" to describe the morphology of the bacterial community.