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Table 3: Animal evidence that biofilm delays wound healing from porcine, murine and rabbit ear wound models

From: Biofilm delays wound healing: A review of the evidence

Model Biofilm species Observations Reference
Porcine acute wound S. aureus Challenge with antimicrobial agents confirmed the recalcitrance of biofilm bacteria Serralta et al. (2001)[34]
Porcine acute wound S. aureus Indirect evidence of delayed healing, with polymorphonucleocytes observed on the surface of, but not within, biofilm Davis et al. (2008)[35]
Porcine acute wound Methicillin-resistant S. aureus (MRSA) Greater healing delays were observed due to biofilm formed by passaged MRSA strains than by parent strains; passaged strain was observed to form more biofilm than parent strain Roche et al. (2012)[36]
Porcine partial-thickness wound MRSA, P . aeruginosa Interactions between MRSA and P. aeruginosa were observed, delaying healing due to suppression of epithelialization and expression of virulence factors Pastar et al. (2013)[37]
Murine burn P. aeruginosa A biofilm-forming factor established in vitro was a key virulence factor in vivo Rashid et al. (2000)[38]
Murine burn P. aeruginosa Microscopic biofilm that was not readily removed by rinsing with saline Schaber et al. (2007)[39]
Murine diabetic chronic wound P. aeruginosa (In vitro then inoculated) biofilm significantly delayed healing compared to controls; health parameters in biofilm-colonized mice were normal Zhao et al. (2010)[40]
Murine diabetic chronic wound P. aeruginosa (In vitro then inoculated) biofilm-colonized wounds had high levels of inflammatory cells; 8 weeks for all biofilm-colonized wounds to heal, compared to 4 weeks for controls Zhao et al. (2012)[41]
Murine diabetic chronic wound P. aeruginosa Biofilm significantly delayed wound healing, even in diabetic mice treated with insulin Watters et al. (2012)[42]
Murine chronically infected surgical wound P. aeruginosa Biofilm was highly resistant to antibiotics and undiluted sodium hypochlorite once established over several days Wolcott et al. (2010)[32]
Murine chronically infected surgical wound S. aureus, P. aeruginosa, Enterococcus faecalis, Finegoldia magna (In vitro then inoculated) polymicrobial biofilm was maintained for 12 days, and delayed healing more than P. aeruginosa biofilm, as measured by wound closure Dalton et al. (2011)[43]
Murine splinted wound S. aureus or Staphylococcus epidermidis Biofilms significantly delayed epithelialization; inhibition of biofilm restored normal wound healing Schierle et al. (2009)[44]
Rabbit ear wound S. aureus Biofilm and active infection significantly delayed epithelialization and granulation tissue formation; biofilm-colonized wounds expressed significantly lower levels of inflammatory cytokines than infected wounds Gurjala et al. (2011)[22]
Rabbit ear wound P. aeruginosa Biofilm significantly delayed epithelialization and granulation tissue formation; debridement, lavage and silver sulphadiazine in combination were more effective at restoring healing than individua treatments Seth et al. (2012a)[45]
Rabbit ischemic ear wound Klebsiella pneumoniae Biofilm formed readily in ischemic wounds but not in non-ischemic wounds where neutrophils and macrophages were seen Seth et al. (2012b)[46]
Rabbit ischemic ear wound K. pneumoniae, S. aureus, P. aeruginosa K. pneumoniae biofilm was least virulent, P. aeruginosa biofilm most virulent, measured by healing inhibition and inflammatory responses; EPS-deficient P. aeruginosa did not delay healing Seth et al. (2012c)[47]
Rabbit ear wound S. aureus, P. aeruginosa Two-species biofilm elicited significantly elevated inflammatory response and impaired epithelialization and granulation tissue formation compared to single-species biofilm Seth et al. (2012d)[48]