Biofilms in Chronic Wounds: Current
Research and Future Direction
ABSTRACT
Chronic wounds continue to be a significant healthcare problem.
Although myriad factors have been implicated in impaired wound healing, recent research has focused on the role of matrix-based bacterial communities called biofilms that are often associated with chronic wounds. Various in vitro and in vivo models have been developed to study the role of biofilms in non-healing wounds. Basic science and clinical studies suggest that effective eradication of pathogenic biofilms requires multimodality strategies including serial debridement, systemic antibiotics and biofilm-based wound care. More recently, novel strategies targeting molecular signaling pathways and immunotherapy have developed for biofilm eradication. As researchers continue to elucidate critical host-bacteria interactions that may underlie wound chronicity, new therapies may emerge to combat this growing biomedical burden.
Key words: Chronic wounds, Biofilms, Quorum-sensing, Extracellular polymeric substances
INTRODUCTION
Chronic wounds continue to present a major challenge to both clinicians and patients and represent a significant financial burden to society[1–12]. Despite the growing interest in wound–related research,
Oregon Health & Science University Department of Surgery, 3181 SW Sam Jackson
Park Road Portland, OR 97239 USA.
*Corresponding author: E-mail: wongvi@ohsu.edu
2 Biotechnology Vol. 3: Plant Biotechnology the understanding of chronic wound pathophysiology remains incomplete[13–19]. Biofilms are three–dimensional bacterial aggregates on the wound surface that have been shown to delay wound healing and sustain the progression of chronic wounds[20–26]. A better understanding of the interplay between biofilms and chronic wounds may guide novel strategies to prevent biofilm formation and effectively treat chronic wounds. In this chapter, we aim to evaluate the role of biofilms in
References: Probiotics L. plantarum shown to inhibit Valdéz et al., 2005; P pro–inflammatory cytokine IL–8 Gene therapy Targeting SMU.940 gene inhibits Falsetta et al., 2012 Gordois A., Scuffham, P. and Shearer, A. (2003). The healthcare costs of diabetic peripheral neuropathy in the US Carter, M.J. and Warriner, R.A.III. (2009). Evidence–based medicine in wound care: Time for a new paradigm Beckrich, K. and Aronovitch, S.A. (1999). Hospital–acquired pressure ulcers: A comparison of costs in medical versus surgical patients Church, D., Elsayed, S. and Reid, O. (2006). Burn wound infections. Clin. Microbiol. Agnihotri, N., Gupta, V. and Joshi, R.M. (2004). Aerobic bacterial isolates from burn wound infections and their antibiograms: A five–year study Armour, A.D., Shankowsky, H.A. and Swanson, T. (2007). The impact of nosocomially–acquired resistant Pseudomonas aeruginosa infection in a burn Landi, F., Onder, G. and Russo, A. (2007). Pressure ulcer and mortality in frail elderly people living in community Landi, F., Sgadari, A. and Bernabei, R. (1996). Pressure ulcers. Ann. Intern. Med., 125(5): 422–425. Perencevich, E.N., Sands, K.E. and Cosgrove, S.E. (2003). Health and economic impact of surgical site infections diagnosed after hospital discharge Ramsey, S.D., Newton, K. and Blough, D. (1999). Patient–level estimates of the cost of complications in diabetes in a managed–care population, Ramsey, S.D., Newton, K. and Blough, D. (1999). Incidence, outcomes, and cost of foot ulcers in patients with diabetes Boyko, E.J., Ahroni, J.H. and Smith, D.G. (1996). Increased mortality associated with diabetic foot ulcer Werdin, F., Tennenhaus, M. and Schaller, H.E. (2009). Evidence–based management strategies for treatment of chronic wounds Mustoe, T.E., O’Shaughnessy, K. and Kloeters, O. (2006). Chronic wound pathogenesis and current treatment strategies: A unifying hypothesis Menke, N.B., Ward, K.R. and Witten, T.M. (2007). Impaired wound healing. Clin. Mustoe, T.A. (2004). Understanding chronic wounds: A unifying hypothesis on their pathogenesis and implications for therapy Peirce, S.M., Skalak, T.C. and Rodeheaver, G.T. (2000). Ischemia–reperfusion injury in chronic pressure ulcer formation: A skin model in the rat Wilson, J.A. and Clark, J.J. (2003). Obesity: Impediment to wound healing. Crit. Walker, J.T., Verran, J. and Boyle, B. (2001). Microscopy methods to investigate the structure of potable water biofilms Walker J.T. and Percival, S.L. (2001). Control of biofouling in drinking water systems Percival, S.L., Thomas, J.G., and Williams, D.W. (2010). The world of microbiology and biofilmology Percival, S.L. and Rogers, AA. (2005). The significance and role of biofilms in chronic wounds Percival, S.L., Kite, P. and Stickler, D. (2009). The use of urinary catheters and control of biofilms using TEDTA Percival, S. and Bowler, P. (2004). Biofilms and their potential role in wound healing. Percival, S.L. and Cutting, K.F. (2009). Biofilms: Possible strategies for suppression in chronic wounds Costerton, J.W., Stewart, P.S. and Greenberg, E.P. (1999). Bacterial biofilms: A common cause of persistent infections Lynch, A.S. and Robertson, G.T. (2008). Bacterial and fungal biofilm infections. Percival, S.L. and Walker, J.T. (1999). Biofilms and public health significance. Percival, S.L., Kite, P. and Donlan, R.M. (2005). Assessing the effectiveness of tetrasodium ethylenediaminetetraacetic acid as a novel central venous catheter Kite, P., Eastwood, K. and Sugden, S. (2004). Use of in–vivo generated biofilms from haemodialysis catheters to test the efficacy of a novel antimicrobial Davies, D., Chakrabarty, A. and Geesey, G. (1993). Exopolysaccharide production in biofilms: Substratum activation of alginate geen expression by Pseudomonas Leid, J.G., Willson, C.J. and Shirtliff, M.E. (2005). The exopolysaccharide alginate protects Pseudomonas aeruginosa biofilm bacteria from IFN–gamma mediated Wolcott, R.D., Cox, S.B. and Dowd, S.E. (2010). Healing and healing rates of chronic wounds in the age of molecular pathogen diagnostics Monroe, D. (2007). Looking for chinks in the armor of bacterial biofilms. Plos. Biol., 5(11): e307. Schaber, J., Triffo, W. and Suh, S. (2007). Pseudomonas aeruginosa forms biofilms 20 Biotechnology Vol