Why chronic wounds will not heal: a novel hypothesis

Abstract

The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.

The Limitations of In Vitro Experimentation in Understanding Biofilms and Chronic Infection

“…Recent studies have shown how P. aeruginosa non-attached biofilm aggregates form in liquid batch cultures, and that they have the same characteristics as surface attached biofilms when it comes to antibiotic tolerance and resilience towards PMNs [62,63]. The absence of such surfaces in surface wounds means the bacterial cells assume a biofilm lifestyle within a self-contained aggregate, devoid of surface attachment [64,65]. There have been a number of in vitro studies that have observed steep chemical gradients (notably oxygen) throughout biofilms, which leads to a heterogenic growth pattern [26,32].…”

Garlic ointment inhibits biofilm formation by bacterial pathogens from burn wounds

“…Within an infected wound, bacterial pathogens frequently exist within protective structures termed biofilms (Bjarnsholt et al, 2008;James et al, 2008). Biofilms are embedded in a glycocalyx, which is a combination of bacterial secreted extracellular polysaccharides that form a protective matrix adhering to the host's surrounding tissues (Stoodley et al, 2002;Sutherland, 2001).…”

Early debridement and skin grafting in diabetic ulcer to reduce morbidity.

“…7 Bjarnsholt T and et al said that pseudomonas plays the important role in diabetic foot infection. 8 George et al stated that diabetes accounts for up to 50 per cent of non-traumatic leg amputations. Foot ulceration unattended is the most common single precursor to amputation.…”