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In Vitro and In Vivo Biofilm Wound Models and Their Application

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Advances in Microbiology, Infectious Diseases and Public Health

Part of the book series: Advances in Experimental Medicine and Biology ((AMIDPH,volume 897))

Abstract

Chronic wounds are wounds which are detained in one or more phases of normal wound healing. It is estimated that 1–2 % of the population of developed countries will experience a chronic wound during their lifetime and this number is expected to increase given the growing world population, increase in age, body mass index and associated diseases such as diabetes and cardiovascular diseases. Although several factors contribute to wound healing, presence of bacterial biofilms significantly affects healing and success of wound treatment. This indicates that wound-care therapies should be directed towards targeting biofilms within chronic wounds. Despite this, the role of biofilms in chronic wound pathogenesis and the effect of wound-care therapies against biofilms within wounds are not well understood. In order to address these issues, appropriate biofilm models are necessary. To this end, several model systems mimicking the conditions observed in a biofilm infected chronic wound have been developed. In this review we present an overview of these different in vitro and in vivo biofilm wound model systems and discuss their advantages and disadvantages.

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References

  • Agostinho A, Hartman A, Lipp C, Parker A, Stewart P, James G (2011) An in vitro model for the growth and analysis of chronic wound MRSA biofilm. J Appl Microbiol 111:1275–1282

    Article  CAS  PubMed  Google Scholar 

  • Akiyama H, Kanzaki H, Tada J, Arata J (1996) Staphylococcus aureus infection on cut wounds in the mouse skin: experimental Staphylococcal botryomycosis. J Dermatol Sci 11:234

    Article  CAS  PubMed  Google Scholar 

  • Akiyama H, Huh WK, Yamasaki O, Oono T, Iwatsuki K (2002) Confocal laser scanning microscopic observation of glycocalyx production by Staphylococcus aureus in mouse skin: does S. aureus generally produce a biofilm on damaged skin? Br J Dermatol 147:879

    Article  CAS  PubMed  Google Scholar 

  • Anderl JN, Franklin MJ, Stewart PS (2000) Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Antimicrob Agents Chemother 44(7):1818–1824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Apidianakis Y, Rahme LG (2009) Drosophila melanogaster as a model host for studying Pseudomonas aeruginosa infection. Nat Protoc 4:1285

    Article  CAS  PubMed  Google Scholar 

  • Asada M, Nakagami G, Minematsu T, Nagase T, Akase T, Huang L, Yoshimura K, Sanada H (2012) Novel models for bacterial colonization and infection of full-thickness wounds in rats. Wound Repair Regen 20:601–610

    PubMed  Google Scholar 

  • Bellas E, Seiberg M, Garlick J, Kaplan DL (2012) In vitro 3D full-thickness skin-equivalent tissue model using silk and collagen biomaterials. Macromol Biosci 12(12):1627–1636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bjarnsholt T, Kirketerp-Moller K, Jensen PO, Madsen KG, Phipps R, Krogfelt K, Høiby N, Givskov M (2008) Why chronic wounds will not heal: a novel hypothesis. Wound Repair Regen 16:2–10

    Article  PubMed  Google Scholar 

  • Bowler PG (1998) The anaerobic and aerobic microbiology of wounds: a review. Wounds 10(6):170–178

    Google Scholar 

  • Bowler PG (2003) The 10(5) bacterial growth guideline: reassessing its clinical relevance in wound healing. Ostomy Wound Manage 49(1):44–53

    PubMed  Google Scholar 

  • Brackman G, Cos P, Maes L, Nelis HJ, Coenye T (2011) Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Antimicrob Agents Chemother 55:2655–2661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brackman G, Demeyer L, Nelis H, Coenye T (2013) Biofilm inhibitory and biofilm eradicating activity of wound care products against Staphylococcus aureus and Staphylococcus epidermidis biofilms in an in vitro chronic wound model. J Appl Microbiol 114:1833–1842

    Article  CAS  PubMed  Google Scholar 

  • Buckingham-Meyer K, Goeres DM, Hamilton MA (2007) Comparative evaluation of biofilm disinfectant efficacy tests. J Microbiol Methods 70(2):236–244

    Article  CAS  PubMed  Google Scholar 

  • Burmølle M, Thomsen TR, Fazli M, Dige I, Christensen L, Homøe P, Tvede M, Nyvad B, Tolker-Nielsen T, Givskov M, Moser C, Kirketerp-Møller K, Johansen HK, Høiby N, Jensen PØ, Sørensen SJ, Bjarnsholt T (2010) Biofilms in chronic infections – a matter of opportunity – monospecies biofilms in multispecies infections. FEMS Immunol Med Microbiol 59(3):324–336

    PubMed  Google Scholar 

  • Charles CA, Ricotti CA, Davis SC, Mertz PM, Kirsner RS (2009) Use of tissue-engineered skin to study in vitro biofilm development. Dermatol Surg 35(9):1334–1341

    Article  CAS  PubMed  Google Scholar 

  • Chen EA, Zhao L, Bamat M, von Borstel R, Mustoe T (1999) Acceleration of wound healing with topically applied deoxyribonucleosides. Arch Surg 134:520–525

    Article  CAS  PubMed  Google Scholar 

  • Chen P, Seth AK, Abercrombie JJ, Mustoe TA, Leung KP (2014) Activity of imipenem against Klebsiella pneumoniae biofilms in vitro and in vivo. Antimicrob Agents Chemother 58(2):1208–1213

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Church D, Elsayed S, Reid O, Winston B, Lindsay R (2006) Burn wound infections. Clin Microbiol Rev 19:403–434

    Article  PubMed  PubMed Central  Google Scholar 

  • Cierny G III, DiPasquale D (2006) Treatment of chronic infection. J Am Acad Orthop Surg 14:S105–S110

    Article  PubMed  Google Scholar 

  • Clutterbuck AL, Cochrane CA, Dolman J, Percival SL (2007) Evaluating antibiotics for use in medicine using a poloxamer biofilm model. Ann Clin Microbiol Antimicrob 6:2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Coenye T, Nelis HJ (2010) In vitro and in vivo model systems to study microbial biofilm formation. J Microbiol Methods 83(2010):89–105

    Article  CAS  PubMed  Google Scholar 

  • Colsky AS, Kirsner RS, Kerdel FA (1998) Microbiologic evaluation of cutaneous wounds in hospitalized dermatology patients. Ostomy Wound Manage 44:40–46

    CAS  PubMed  Google Scholar 

  • Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322

    Article  CAS  PubMed  Google Scholar 

  • Cutting KF (2003) Wound exudate: composition and function. Br J Community Nurs 8(9 Suppl):suppl 4–9

    Google Scholar 

  • Dalton T, Dowd SE, Wolcott RD, Sun Y, Watters C, Griswold JA, Rumbaugh KP (2011) An in vivo polymicrobial biofilm wound infection model to study interspecies interactions. PLoS One 6:e27317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davis SC, Eaglstein WH, Cazzaniga AL, Mertz PM (2001) An octyl- 2-cyanoacrylate formulation speeds healing of partialthickness wounds. Dermatol Surg 27:783–788

    CAS  PubMed  Google Scholar 

  • Davis SC, Ricotti C, Cazzaniga A, Welsh E, Eaglstein WH, Mertz PM (2007) Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo. Wound Repair Regen. 2008 Jan-Feb;16(1):23-9. doi: 10.1111/j.1524-475X.2007.00303.x.

    Google Scholar 

  • Davis SC, Ricotti C, Cazzaniga A, Welsh E, Eaglstein WH, Mertz PM (2008) Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo. Wound Repair Regen 16(1):23–9. doi:10.1111/j.1524-475X.2007.00303.x

  • De Breij A, Haisma EM, Rietveld M, El Ghalbzouri A, van den Broek PJ, Dijkshoorn L, Nibbering PH (2012) Three-dimensional human skin equivalent as a tool to study Acinetobacter baumannii colonization. Antimicrob Agents Chemother 56(5):2459–2464

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • DeLeon S, Clinton A, Fowler H, Everett J, Horswill AR, Rumbaugh KP (2014) Synergistic interactions of Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro wound model. Infect Immun 82(11):4718–4728

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dhall S, Do D, Garcia M, Wijesinghe DS, Brandon A, Kim J, Sanchez A, Lyubovitsky J, Gallagher S, Nothnagel EA, Chalfant CE, Patel RP, Schiller N, Martins-Green M (2014) A novel model of chronic wounds: importance of redox imbalance and biofilm-forming bacteria for establishment of chronicity. PLoS One 9(10), e109848. doi:10.1371/journal.pone.0109848

  • Donlan RM, Piede JA, Heyes CD, Sanii L, Murga R, Edmonds P, El-Sayed I, El-Sayed MA (2004) Model system for growing and quantifying Streptococcus pneumonia biofilms in situ and in real time. Appl Environ Microbiol 708:4980–4988

    Article  CAS  Google Scholar 

  • Douglas EL, Piwowarczyk W, Pamula E, Liskova J, Schaubroeck D, Leeuwenburgh SCG, Brackman G, Balcaen L, Detsch R, Cholewa-Kowalska K, Vanhaecke F, Cornelissen R, Coenye T, Boccaccini A, Dubruel P (2014) Injectable self-gelling composites for bone tissue engineering based on gellan gum hydrogel enriched with different bioglasses. Biomed Mater 9(4):045014

    Article  PubMed  CAS  Google Scholar 

  • Dowd SE, Sun Y, Smith E, Kennedy JP, Jones CE, Wolcott R (2009) Effects of biofilm treatments on the multi-species Lubbock chronic wound biofilm model. J Wound Care 18(508):510–512

    Google Scholar 

  • El Ghalbzouri A, Hensbergen P, Gibbs S, Kempenaar J, van der Schors R, Ponec M (2004) Fibroblasts facilitate re-epithelialization in wounded human skin equivalents. Lab Investig 84:102–112

    Article  PubMed  CAS  Google Scholar 

  • El Ghalbzouri A, Siamari R, Willemze R, Ponec M (2008) Leiden reconstructed human epidermal model as a tool for the evaluation of the skin corrosion and irritation potential according to the ECVAM guidelines. Toxicol In Vitro 22:1311–1320

    Article  PubMed  CAS  Google Scholar 

  • Eming SA, Koch M, Krieger A, Brachvogel B, Kreft S, Bruckner-Tuderman L, Krieg T, Shannon JD, Fox JW (2010) Differential proteomic analysis distinguishes tissue repair biomarker signatures in wound exudates obtained from normal healing and chronic wounds. J Proteome Res 9(9):4758–4766

    Article  CAS  PubMed  Google Scholar 

  • Ermolaeva SA, Varfolomeev AF, Chernukha MY, Yurov DS, Vasiliev MM, Kaminskaya AA, Moisenovich MM, Romanova JM, Murashev AN, Selezneva II, Shimizu T, Sysolyatina EV, Shaginyan IA, Petrov OF, Mayevsky EI, Fortov VE, Morfill GE, Naroditsky BS, Gintsburg AL (2011) Bactericidal effects of non-thermal argon plasma in vitro, in biofilms and in the animal model of infected wounds. J Med Microbiol 60(1):75–83

    Article  CAS  PubMed  Google Scholar 

  • Fazli M, Bjarnsholt T, Kirketerp-Moller K, Jorgensen B, Andersen AS, Krogfelt KA, Givskov M, Tolker-Nielsen T (2009) Nonrandom distribution of Pseudomonas aeruginosa and Staphylococcus aureus in chronic wounds. J Clin Microbiol 47:4084–4089

    Article  PubMed  PubMed Central  Google Scholar 

  • Fierheller M, Sibbald RG (2010) A clinical investigation into the relationship between increased periwound skin temperature and local wound infection in patients with chronic leg ulcers. Adv Skin Wound Care 23(8):369–379

    Article  PubMed  Google Scholar 

  • Fux CA, Stoodley P, Hall-Stoodley L, Costerton JW (2003) Bacterial biofilms: a diagnostic and therapeutic challenge. Expert Rev Anti Infect Ther 1:667–683

    Article  PubMed  Google Scholar 

  • Garcia-Fernandez MJ, Brackman G, Coenye T, Concheiro A, Alvarez-Lorenzo C (2013) Antiseptic cyclodextrin-functionalized hydrogels and gauzes for loading and delivery of benzalkonium chloride. Biofouling 29:261–271

    Article  CAS  PubMed  Google Scholar 

  • Gjodsbol K, Christensen JJ, Karlsmark T, Jorgensen B, Klein BM, Krogfelt KA (2006) Multiple bacterial species reside in chronic wounds: a longitudinal study. Int Wound J 3:225–231

    Article  PubMed  Google Scholar 

  • Gordillo GM, Bernatchez SF, Diegelmann R, Di Pietro LA, Eriksson E, Hinz B, Hopf HW, Kirsner R, Liu P, Parnell LK, Sandusky GE, Sen CK, Tomic-Canic M, Volk SW, Baird A (2013) Preclinical models of wound healing: is man the model? Proceedings of the Wound Healing Society Symposium. AdvWound Care (New Rochelle) 2:1–4

    Google Scholar 

  • Gottrup F (2004) A specialized wound healing center concept: importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds. Am J Surg 187:38S–43S

    Article  PubMed  Google Scholar 

  • Greenman J, Thorn RM, Saad S, Austin AJ (2006) In vitro diffusion bed, 3-day repeat challenge ‘capacity’ test for antimicrobial wound dressings. Int Wound J 3:322–329

    Article  PubMed  Google Scholar 

  • Gurjala AN, Geringer MR, Seth AK, Hong SJ, Smeltzer MS, Galiano RD, Leung KP, Mustoe TA (2011) Development of a novel, highly quantitative in vivo model for the study of biofilm-impaired cutaneous wound healing. Wound Repair Regen 19:400

    Article  PubMed  Google Scholar 

  • Gawande PV, Clinton AP, LoVetri K, Yakandawala N, Rumbaugh KP, Madhyastha S (2014 Mar 5) Antibiofilm efficacy of DispersinB(®) wound spray used in combination with a silver wound dressing. Microbiol Insights 7:9–13

    Google Scholar 

  • Haisma EM, Rietveld MH, de Breij A, van Dissel JT, El Ghalbzouri A, Nibbering PH (2013) Inflammatory and antimicrobial responses to methicillin- resistant Staphylococcus aureus in an in vitro wound infection model. PLoS One 8(12):e82800

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hakonen B, Lönnberg LK, Larkö E, Blom K (2014) A novel qualitative and quantitative biofilm assay based on 3D soft tissue. Int J Biomat. Article ID 768136

    Google Scholar 

  • Halder P, Nasabi M, Lopez FJ, Jayasuriya N, Bhattacharya S, Deighton M, Mitchell A, Bhuiyan MA (2013) A novel approach to determine the efficacy of patterned surfaces for biofouling control in relation to its microfluidic environment. Biofouling 2013(29):697–713

    Article  Google Scholar 

  • Hammond AA, Miller KG, Kruczek CJ, Dertien J, Colmer-Hamood JA, Griswold JA, Horswill AR, Hamood AN (2011) An in vitro biofilm model to examine the effect of antibiotic ointments on biofilms produced by burn wound bacterial isolates. Burns 37(2):312–321

    Article  PubMed  PubMed Central  Google Scholar 

  • Harrison-Balestra C, Cazzaniga AL, Davis SC, Mertz PM (2003) A wound-isolated Pseudomonas aeruginosa grows a biofilm in vitro within 10 hours and is visualized by light microscopy. Dermatol Surg 29:631–635

    PubMed  Google Scholar 

  • Hill KE, Malic S, McKee R, Rennison T, Keith GH, Williams DW, Thomas DW (2010) An in vitro model of chronic wound biofilms to test wound dressings and assess antimicrobial susceptibilities. J Antimicrob Chemother 65:1195–1206

    Article  CAS  PubMed  Google Scholar 

  • Holland DB, Bojar RA, Jeremy AH, Ingham E, Holland KT (2008) Microbial colonization of an in vitro model of a tissue engineered human skin equivalent--a novel approach. FEMS Microbiol Lett 279:110–115

    Article  CAS  PubMed  Google Scholar 

  • Holland DB, Bojar RA, Farrar MD, Holland KT (2009) Differential innate immune responses of a living skin equivalent model colonized by Staphylococcus epidermidis or Staphylococcus aureus. FEMS Microbiol Lett 290:149–155

    Article  CAS  PubMed  Google Scholar 

  • James GA, Swogger E, Wolcott R, Pulcini E, Secor P, Sestrich J, Costerton JW, Stewart PS (2008) Biofilms in chronic wounds. Wound Repair Regen 16:37–44

    Article  PubMed  Google Scholar 

  • Kim H, Izadjoo MJ (2015) Antibiofilm efficacy evaluation of a bioelectric dressing in mono- and multi-species biofilms. J Wound Care 24(Suppl 2):S10–S14

    Article  PubMed  Google Scholar 

  • Kim J, Hegde M, Jayaraman A (2010a) Microfluidic co-culture of epithelial cells and bacteria for investigating soluble signal-mediated interactions. J Vis Exp 38:1749

    PubMed  Google Scholar 

  • Kim J, Hegde M, Jayaraman A (2010b) Co-culture of epithelial cells and bacteria for investigating host–pathogen interactions. Lab Chip 10:43–50

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Park HD, Chung S (2012) Microfluidic approaches to bacterial biofilm formation. Molecules 17(9818):9834

    Google Scholar 

  • Kirker KR, Secor PR, James GA, Fleckman P, Olerud JE, Stewart PS (2009) Loss of viability and induction of apoptosis in human keratinocytes exposed to Staphylococcus aureus biofilms in vitro. Wound Repair Regen 17:690–699

    Article  PubMed  PubMed Central  Google Scholar 

  • Kirker KR, James GA, Fleckman P, Olerud JE, Stewart PS (2012) Differential effects of planktonic and biofilm MRSA on human fibroblasts. Wound Repair Regen 20(2):253–261

    Article  PubMed  PubMed Central  Google Scholar 

  • Kirketerp-Møller K, Gottrup F (2009) [Bacterial biofilm in chronic wounds]. Ugeskr Laeger 171:1097

    PubMed  Google Scholar 

  • Kirketerp-Moller K, Jensen PO, Fazli M, Madsen KG, Pedersen J, Moser C, Tolker-Nielsen T, Hoiby N, Givskov M, Bjarnsholt T (2008) Distribution, organization, and ecology of bacteria in chronic wounds. J Clin Microbiol 46(8):2717–2722

    Article  PubMed  PubMed Central  Google Scholar 

  • Kostenko V, Lyczak J, Turner K, Martinuzzi RJ (2010) Impact of silver-containing wound dressings on bacterial biofilm viability and susceptibility to antibiotics during prolonged treatment. Antimicrob Agents Chemother 54(12):5120–5131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kucera J, Sojka M, Pavlik V, Szuszkiewicz K, Velebny V, Klein P (2014) Multispecies biofilm in an artificial wound bed—a novel model for in vitro assessment of solid antimicrobial dressings. J Microbiol Methods 103(2014):18–24

    Article  CAS  PubMed  Google Scholar 

  • Lazarus GS, Cooper DM, Knighton DR, Margolis DJ, Pecoraro RE, Rodeheaver G, Robson MC (1994) Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 130:489–493

    Article  CAS  PubMed  Google Scholar 

  • Leung KP, D'Arpa P, Seth AK, Geringer MR, Jett M, Xu W, Hong SJ, Galiano RD, Chen T, Mustoe TA (2014) Dermal wound transcriptomic responses to Infection with Pseudomonas aeruginosa versus Klebsiella pneumoniae in a rabbit ear wound model. BMC Clin Pathol 14:20. doi:10.1186/1472-6890-14-20

  • Lipp C, Kirker K, Agostinho A, James G, Stewart P (2010) Testing wound dressings using an in vitro wound model. J Wound Care 19:220–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luna-Straffon MA, Contreras-García A, Brackman G, Coenye T, Concheiro A, Alvarez-Lorenzo C, Bucio E (2014) Wound debridement and antibiofilm properties of gamma-ray DMAEMA-grafted cotton gauzes. Cellulose J 21:3767–3779

    Article  CAS  Google Scholar 

  • Malic S, Hill KE, Playle R, Thomas DW, Williams DW (2011) In vitro interaction of chronic wound bacteria in biofilms. J Wound Care 20(12):569–570

    Article  CAS  PubMed  Google Scholar 

  • Merritt JH, Kadouri DE, O’Toole GA (2011) Growing and analyzing static biofilms. Curr Protoc Microbiol 22:1–8

    Google Scholar 

  • Miller KG, Tran PL, Haley CL, Kruzek C, Colmer-Hamood JA, Myntti M, Hamood AN (2014) Next science wound gel technology, a novel agent that inhibits biofilm development by gram-positive and gram-negative wound pathogens. Antimicrob Agents Chemother 58(6):3060–3072

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mogford JE, Tawil B, Jia S, Mustoe TA (2009) Fibrin sealant combined with fibroblasts and platelet derived growth factor enhance wound healing in excisional wounds. Wound Repair Regen 17:405–410

    Article  PubMed  Google Scholar 

  • Mustoe TA, Pierce GF, Morishima C, Deuel TF (1991) Growth factor-induced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model. J Clin Invest 87:694–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagami G, Sanada H, Sugama J, Morohoshi T, Ikeda T, Ohta Y (2008) Detection of Pseudomonas aeruginosa quorum sensing signals in an infected ischemic wound: an experimental study in rats. Wound Repair Regen 16(1):30–36. doi:10.1111/j.1524-475X.2007.00329.x

    Article  PubMed  Google Scholar 

  • Ngo QD, Vickery K, Deva AK (2012) The effect of topical negative pressure on wound biofilms using an in vitro wound model. Wound Repair Regen 20(1):83–90

    Article  PubMed  Google Scholar 

  • Nguyen KT, Seth AK, Hong SJ, Geringer MR, Xie P, Leung KP, Mustoe TA, Galiano RD (2013) Deficient cytokine expression and neutrophil oxidative burst contribute to impaired cutaneous wound healing in diabetic, biofilm-containing chronic wounds. Wound Repair Regen 21(6):833–841

    Article  PubMed  Google Scholar 

  • Nichols DP, Caceres S, Caverly L, Fratelli C, Kim SH, Malcolm K, Poch KR, Saavedra M, Solomon G, Taylor-Cousar J, Moskowitz S, Nick JA (2013) Effects of azithromycin in Pseudomonas aeruginosa burn wound infection. J Surg Res 183(2):767–776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nidadavolu P, Amor W, Tran PL, Dertien J, Colmer-Hamood JA, Hamood AN (2012) Garlic ointment inhibits biofilm formation by bacterial pathogens from burn wounds. J Med Microbiol 61(Pt 5):662–671

    Article  PubMed  Google Scholar 

  • Nusbaum AG, Gil J, Rippy MK, Warne B, Valdes J, Claro A, Davis SC (2012 Aug) Effective method to remove wound bacteria: comparison of various debridement modalities in an in vivo porcine model. J Surg Res 176(2):701–7. doi:10.1016/j.jss.2011.11.1040

  • Pastar I, Nusbaum AG, Gil J, Patel SB, Chen J, Valdes J, Stojadinovic O, Plano LR, Tomic-Canic M, Davis SC (2013) Interactions of methicillin resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in polymicrobial wound infection. PLoS One 8(2), e56846. doi:10.1371/journal.pone.0056846

  • Percival SL, Bowler PG, Dolman J (2007) Antimicrobial activity of silver-containing dressings on wound microorganisms using an in vitro biofilm model. Int Wound J 4(2):186–191

    Article  PubMed  Google Scholar 

  • Percival SL, Thomas JG, Slone W, Linton S, Corum L, Okel T (2011) The efficacy of silver dressings and antibiotics on MRSA and MSSA isolated from burn patients. Wound Repair Regen 19(6):767–774

    Article  PubMed  Google Scholar 

  • Petreaca ML, Do D, Dhall S, McLelland D, Serafino A, Lyubovitsky J, Schiller N, Martins-Green MM (2012) Deletion of a tumor necrosis superfamily gene in mice leads to impaired healing that mimics chronic wounds in humans. Wound Repair Regen 20(3):353–366

    Article  PubMed  PubMed Central  Google Scholar 

  • Pechter PM, Gil J, Valdes J, Tomic-Canic M, Pastar I, Stojadinovic O, Kirsner RS, Davis SC (2012) Keratin dressings speed epithelialization of deep partial-thickness wounds. Wound Repair Regen. 2012 Mar-Apr;20(2):236-42. doi: 10.1111/j.1524-475X.2012.00768.x.

    Google Scholar 

  • Phillips PL, Yang Q, Sampson EM, Schultz GS (2010) Effects of antimicrobial agents on an in vitro biofilm model of skin wounds. In: Sen CK (ed) Advances in wound care. Wound Healing Society Yearbook Publication. Mary Ann Liebert Inc. Publishers, New Rochelle, pp 299–304.

    Google Scholar 

  • Phillips P, Yang Q, Sampson E, Progulske-Fox A, Antonelli P, Shouquang J, Schultz G (2013) Development of a novel ex vivo porcine skin explant model for the assessment of mature bacterial biofilms. Wound Repair Regen 21:704–714

    Article  PubMed  Google Scholar 

  • Pratten J, Wilson M (1999) Antimicrobial susceptibility and composition of microcosm dental plaques supplemented with sucrose. Antimicrob Agents Chemother 43:1595–1599

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rao N, Lipsky BA (2007) Optimising antimicrobial therapy in diabetic foot infections. Drugs 67:195–214

    Article  CAS  PubMed  Google Scholar 

  • Rashid MH, Rumbaugh K, Passador L, Davies DG, Hamood AN, Iglewski BH, Kornberg A (2000) Polyphosphate kinase is essential for biofilm development, quorum sensing, and virulence of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 97:9636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rhoads DD, Wolcott RD, Sun Y, Dowd SE (2012) Comparison of culture and molecular identification of bacteria in chronic wounds. Int J Mol Sci 13(3):2535–2550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robson MC (1997) Wound infection. A failure of wound healing caused by an imbalance of bacteria. Surg Clin North Am 77:637–650

    Article  CAS  PubMed  Google Scholar 

  • Roche ED, Renick PJ, Tetens SP, Carson DL (2012a) A model for evaluating topical antimicrobial efficacy against methicillin-resistant Staphylococcus aureus biofilms in superficial murine wounds. Antimicrob Agents Chemother 56(8):4508–4510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roche ED, Renick PJ, Tetens SP, Ramsay SJ, Daniels EQ, Carson DL (2012b) Increasing the presence of biofilm and healing delay in a porcine model of MRSA-infected wounds. Wound Repair Regen 20(4):537–543

    PubMed  Google Scholar 

  • Romanelli M, Gaggio G, Coluccia M, Rizzello F, Piaggesi A (2002) Technological advances in wound bed measurements. Wounds 14(2):58–66

    Google Scholar 

  • Roy S, Elgharably H, Sinha M, Ganesh K, Chaney S, Mann E, Miller C, Khanna S, Bergdall VK, Powell HM, Cook CH, Gordillo GM, Wozniak DJ, Sen CK (2014) Mixed-species biofilm compromises wound healing by disrupting epidermal barrier function. J Pathol 233(4):331–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rumbaugh KP, Griswold JA, Iglewski BH, Hamood AN (1999) Contribution of quorum sensing to the virulence of Pseudomonas aeruginosa in burn wound infections. Infect Immun 67:5854–5862

    CAS  PubMed  PubMed Central  Google Scholar 

  • Said HK, Hijjawi J, Roy N, Mogford J, Mustoe T (2005) Transdermal sustained-delivery oxygen improves epithelial healing in a rabbit ear wound model. Arch Surg 140:998–1004

    Article  PubMed  Google Scholar 

  • Sato K, Sasaki N, Svahn HA, Sato K (2014) Microfluidics for nano-pathophysiology. Adv Drug Deliv Rev 74:115–121

    Article  CAS  PubMed  Google Scholar 

  • Schierle CF, De la Garza M, Mustoe TA, Galiano RD (2009) Staphylococcal biofilms impair wound healing by delaying reepithelialization in a murine cutaneous wound model. Wound Repair Regen 17:354

    Article  PubMed  Google Scholar 

  • Schultz GS, Barillo DJ, Mozingo DW, Chin GA, Wound Bed Advisory Board Members (2004) Wound bed preparation and a brief history of TIME. Int Wound J 1:19–32

    Article  PubMed  Google Scholar 

  • Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT (2009) Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen 17:763–771

    Google Scholar 

  • Seth AK, Geringer MR, Hong SJ, Leung KP, Mustoe TA, Galiano RD (2012) In vivo modeling of biofilm-infected wounds: a review. J Surg Res 178(1):330–338

    Article  PubMed  Google Scholar 

  • Shepherd J, Douglas I, Rimmer S, Swanson L, MacNeil S (2009) Development of three-dimensional tissue engineered models of bacterial infected human skin wounds. Tissue Eng Part C Methods 15:475–484

    Article  PubMed  Google Scholar 

  • Simonetti O, Cirioni O, Ghiselli R, Goteri G, Scalise A, Orlando F, Silvestri C, Riva A, Saba V, Madanahally KD, Offidani A, Balaban N, Scalise G, Giacometti A (2008) RNAIII-Inhibiting peptide enhances healing of wounds infected with methicillin-resistant Staphyloccus aureus. Antimicrob Agents Chemother 52:2205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sullivan TP, Eaglstein WH, Davis SC, Mertz P (2001) The pig as a model for human wound healing. Wound Repair Regen 9(2):66–76

    Article  CAS  PubMed  Google Scholar 

  • Summerfield A, Meurens F, Ricklin ME (2014) The immunology of the porcine skin and its value as a model for human skin. Mol Immunol. http://dx.doi.org/10.1016/j.molimm.2014.10.023

  • Sun Y, Dowd SE, Smith E, Rhoads DD, Wolcott RD (2008) In vitro multispecies Lubbock chronic wound biofilm model. Wound Repair Regen 16:805–813

    Article  PubMed  Google Scholar 

  • Sun Y, Smith E, Wolcott R, Dowd SE (2009) Propagation of anaerobic bacteria within an aerobic multi-species chronic wound biofilm model. J Wound Care 18:426–431

    Article  CAS  PubMed  Google Scholar 

  • Terry J, Neethirajan S (2014) A novel microfluidic wound model for testing antimicrobial agents against Staphylococcus pseudintermedius biofilms. J Nanobiotechnol 12:1

    Article  CAS  Google Scholar 

  • Thompson MG, Black CC, Pavlicek RL, Honnold CL, Wise MC, Alamneh YA, Moon JK, Kessler JL, Si Y, Williams R, Yildirim S, Kirkup BC Jr, Green RK, Hall ER, Palys TJ, Zurawski DV (2014) Validation of a novel murine wound model of Acinetobacter baumannii infection. Antimicrob Agents Chemother 58(3):1332–1342

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thorn RM, Greenman J (2009) A novel in vitro flat-bed perfusion biofilm model for determining the potential antimicrobial efficacy of topical wound treatments. J Appl Microbiol 107:2070–2079

    Article  CAS  PubMed  Google Scholar 

  • Thorn RM, Nelson SM, Greenman J (2007) Use of a bioluminescent Pseudomonas aeruginosa strain within an in vitro microbiological system, as a model of wound infection, to assess the antimicrobial efficacy of wound dressings by monitoring light production. Antimicrob Agents Chemother 51:3217–3224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thorn RM, Austin AJ, Greenman J, Wilkins JP, Davis PJ (2009) In vitro comparison of antimicrobial activity of iodine and silver dressings against biofilms. J Wound Care 18(8):343–346

    Article  CAS  PubMed  Google Scholar 

  • Torkian BA, Yeh AT, Engel R, Sun CH, Tromberg BJ, Wong BJF (2004) Modeling aberrant wound healing using tissue-engineered skin constructs and multiphoton microscopy. Arch Facial Plast Surg 6:180–187

    Article  PubMed  Google Scholar 

  • Trengove NJ, Langton SR, Stacey MC (1996) Biochemical analysis of wound fluid from nonhealing and healing chronic leg ulcers. Wound Repair Regen 4(2):234–239

    Article  CAS  PubMed  Google Scholar 

  • Trengove NJ, Stacey MC, MacAuley S, Bennett N, Gibson J, Burslem F, Murphy G, Schultz G (1999) Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors. Wound Repair Regen 7(6):442–452

    Article  CAS  PubMed  Google Scholar 

  • Trøstrup H, Thomsen K, Christophersen LJ, Hougen HP, Bjarnsholt T, Jensen PØ, Kirkby N, Calum H, Høiby N, Moser C (2013) Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model. Wound Repair Regen 21(2):292–299

    Article  PubMed  Google Scholar 

  • Turner KH, Everett J, Trivedi U, Rumbaugh KP, Whiteley M (2014 Jul 24) Requirements for Pseudomonas aeruginosa acute burn and chronic surgical wound infection. PLoS Genet 10(7), e1004518. doi:10.1371/journal.pgen.1004518

  • Valente PM, Deva A, Ngo Q, Vickery K (2014) The increased killing of biofilms in vitro by combining topical silver dressings with topical negative pressure in chronic wounds. Int Wound J. doi:10.1111/iwj.12248

  • Watters C, Everett JA, Haley C, Clinton A, Rumbaugh KP (2014) Insulin treatment modulates the host immune system to enhance Pseudomonas aeruginosa wound biofilms. Infect Immun 82(1):92–100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Welss T, Basketter DA, Schröder KR (2004) In vitro skin irritation: facts and future. State of the art review of mechanisms and models. Toxicol In Vitro 18(3):231–243

    Google Scholar 

  • Werthén M, Henriksson L, Jensen PØ, Sternberg C, Givskov M, Bjarnsholt T (2010) An in vitro model of bacterial infections in wounds and other soft tissues. APMIS 118(2):156–164

    Article  PubMed  Google Scholar 

  • White RJ, Cutting KF (2006) Critical colonization--the concept under scrutiny. Ostomy Wound Manage 52(11):50–56

    PubMed  Google Scholar 

  • Wolcott RD, Rumbaugh KP, James G, Schultz G, Phillips P, Yang Q, Watters C, Stewart PS, Dowd SE (2010a) Biofilm maturity studies indicate sharp debridement opens a time- dependent therapeutic window. J Wound Care 19(8):320–328

    Article  CAS  PubMed  Google Scholar 

  • Wolcott RD, Rhoads DD, Bennett ME, Wolcott BM, Gogokhia L, Costerton JW, Dowd SE (2010b) Chronic wounds and the medical biofilm paradigm. J Wound Care 19:45–53

    Article  CAS  PubMed  Google Scholar 

  • Woods J, Boegli L, Kirker KR, Agostinho AM, Durch AM, Delancey Pulcini E, Stewart PS, James GA (2012) Development and application of a polymicrobial, in vitro, wound biofilm model. J Appl Microbiol 112(5):998–1006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Q, Phillips PL, Sampson EM, Progulske-Fox A, Jin S, Antonelli P, Schultz GS (2013) Development of a novel ex vivo porcine skin explant model for the assessment of mature bacterial biofilms. Wound Repair Regen 21(5):704–714

    Article  PubMed  Google Scholar 

  • Zhang M, Li H, Ma H, Qin J (2013) A simple microfluidic strategy for cell migration assay in an in vitro wound-healing model. Wound Repair Regen 2013(21):897–903

    Article  Google Scholar 

  • Zhao G, Hochwalt PC, Usui ML, Underwood RA, Singh PK, James GA, Stewart PS, Fleckman P, Olerud JE (2010) Delayed wound healing in diabetic (db/db) mice with Pseudomonas aeruginosa biofilm challenge: a model for the study of chronic wounds. Wound Repair Regen 18:467

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge funding by the Fund for Scientific Research – Flanders (FWO-Vlaanderen), by the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen, SBO programme) and the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office.

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  1. Laboratory of Pharmaceutical Microbiology, Ghent University, Ottergemsesteenweg 460, B-9000, Ghent, Belgium

    Gilles Brackman & Tom Coenye

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  1. Gilles Brackman
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  2. Tom Coenye
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Correspondence to Gilles Brackman .

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  1. Microbial Biofilm Laboratory, Fondazione Santa Lucia IRCCS, Rome, Italy

    Gianfranco Donelli

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Brackman, G., Coenye, T. (2015). In Vitro and In Vivo Biofilm Wound Models and Their Application. In: Donelli, G. (eds) Advances in Microbiology, Infectious Diseases and Public Health. Advances in Experimental Medicine and Biology(), vol 897. Springer, Cham. https://doi.org/10.1007/5584_2015_5002

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