Animal models of chronic wound care: the application of biofilms in clinical research

Abstract

Chronic wounds are a substantial clinical problem affecting millions of people worldwide. Pathophysiologically, chronic wounds are stuck in the inflammatory state of healing. The role of bacterial biofilms in suppression and perturbation of host response could be an explanation for this observation. An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure) has to be taken into consideration as underlying pathophysiological mechanisms and comorbidities display tremendous variation in humans. Confounders such as infection, smoking, chronological age, sex, medication, metabolic disturbances, and renal impairment add to the difficulty in gaining systematic and comparable studies on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s), and time of establishment of the infection are well defined in suitable animal models. In addition, several endpoints can be involved for evaluation. Animals do not display chronic wounds in the way that humans do. However, in many cases, animal models can mirror the pathological conditions observed in humans, although discrepancies between human and animal wound repair are obvious. The use of animal models should be refined and replaced whenever possible, and reproducibility and clinical relevance should be strived. This review aimed at giving an overview of the model systems and major findings for inspiration for clinicians and researchers involved in handling chronic nonhealing wounds. Relevant animal models on wound repair are discussed, and our novel wound model on the host/pathogen interplay is presented. In this model, murine wounds are stuck in a polymorphonuclear neutrophil granulocyte-dominated inflammation due to the presence of visually confirmed Pseudomonas aeruginosa biofilm located in the dermis and subcutaneous fatty tissue.

Biofilms and host response – helpful or harmful

“…Large randomized studies on intervention in patients with recalcitrant wounds are a challenge due to strict inclusion criteria. Additionally, extrapolation of results from chronic wounds of one aetiology to another is not feasible as patients often suffer from several diseases . The choice of an adequate control wound for a chronic one is also problematic as the outcome varies between models .…”

What Is the Impact of Depletion of Immunoregulatory Genes on Wound Healing? A Systematic Review of Preclinical Evidence

“…About the wound healing process, mice are organisms applied in studies for wound healing because this model allows the histological monitoring of the process [ 67 ]. Moreover, this model allows the realization of macroscopic, biochemical, and biomechanical measurements [ 68 ]. Despite the advantages of mice models, there are also some negative points to the use of this animal model, such as skin characteristics.…”

Does antibiotic use accelerate or retard cutaneous repair? A systematic review in animal models

“…Additionally, they allow for the realization of macroscopic, biochemical and biomechanical measurements [62]. In our research, the animal most commonly used in the studies was the rat, possibly due to the low cost, and easy handling and accessibility, allowing researchers to use a relatively large number of animals for their experiments, thereby generating a greater degree of reliability in the results [63]. In addition, the area of dorse is higher when compared to mice.…”