Biofilms in Chronic Wound Infections: Innovative Antimicrobial Approaches Using the In Vitro Lubbock Chronic Wound Biofilm Model

Chronic wounds have harmful effects on both patients and healthcare systems. Wound chronicity is attributed to an impaired healing process due to several host and local factors that affect healing pathways. The resulting ulcers contain a wide variety of microorganisms that are mostly resistant to antimicrobials and possess the ability to form mono/poly-microbial biofilms. The search for new, effective and safe compounds to handle chronic wounds has come a long way throughout the history of medicine, which has included several studies and trials of conventional treatments. Treatments focus on fighting the microbial colonization that develops in the wound by multidrug resistant pathogens. The development of molecular medicine, especially in antibacterial agents, needs an in vitro model similar to the in vivo chronic wound environment to evaluate the efficacy of antimicrobial agents. The Lubbock chronic wound biofilm (LCWB) model is an in vitro model developed to mimic the pathogen colonization and the biofilm formation of a real chronic wound, and it is suitable to screen the antibacterial activity of innovative compounds. In this review, we focused on the characteristics of chronic wound biofilms and the contribution of the LCWB model both to the study of wound poly-microbial biofilms and as a model for novel treatment strategies.

[1]  Lokender Kumar,et al.  Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria , 2022, Molecules.

[2]  L. Cellini,et al.  Antimicrobial Combined Action of Graphene Oxide and Light Emitting Diodes for Chronic Wound Management , 2022, International journal of molecular sciences.

[3]  Minhazur Rahman,et al.  Microrheology of Pseudomonas aeruginosa biofilms grown in wound beds , 2022, NPJ biofilms and microbiomes.

[4]  E. Stuermer,et al.  Pulsed low-intensity laser treatment stimulates wound healing without enhancing biofilm development in vitro. , 2022, Journal of photochemistry and photobiology. B, Biology.

[5]  L. Cellini,et al.  Complex Chronic Wound Biofilms Are Inhibited in vitro by the Natural Extract of Capparis spinose , 2022, Frontiers in Microbiology.

[6]  C. Provot,et al.  A Relevant Wound-Like in vitro Media to Study Bacterial Cooperation and Biofilm in Chronic Wounds , 2022, Frontiers in Microbiology.

[7]  Mads Lichtenberg,et al.  Biofilm Survival Strategies in Chronic Wounds , 2022, Microorganisms.

[8]  M. Tomic-Canic,et al.  Novel Diagnostic Technologies and Therapeutic Approaches Targeting Chronic Wound Biofilms and Microbiota , 2022, Current Dermatology Reports.

[9]  J. Mwesigye,et al.  Resistance pattern of infected chronic wound isolates and factors associated with bacterial resistance to third generation cephalosporins at Mbarara Regional Referral Hospital, Uganda , 2021, PloS one.

[10]  H. Girault,et al.  Advances in the Sensing and Treatment of Wound Biofilms , 2021, Angewandte Chemie.

[11]  C. Dunyach-Rémy,et al.  New Adapted In Vitro Technology to Evaluate Biofilm Formation and Antibiotic Activity Using Live Imaging under Flow Conditions , 2021, Diagnostics.

[12]  L. Cellini,et al.  Antimicrobial Peptide L18R Displays a Modulating Action against Inter-Kingdom Biofilms in the Lubbock Chronic Wound Biofilm Model , 2021, Microorganisms.

[13]  O. Zanetti,et al.  Challenges in the management of chronic wound infections. , 2021, Journal of global antimicrobial resistance.

[14]  Yijuan Xu,et al.  A novel chronic wound biofilm model sustaining coexistence of Pseudomonas aeruginosa and Staphylococcus aureus suitable for testing of antibiofilm effect of antimicrobial solutions and wound dressings , 2021, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[15]  S. Debus,et al.  In vitro Activity of Antimicrobial Wound Dressings on P. aeruginosa Wound Biofilm , 2021, Frontiers in Microbiology.

[16]  A. Grumezescu,et al.  Photodynamic Therapy—An Up-to-Date Review , 2021, Applied Sciences.

[17]  J. Overhage,et al.  Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation , 2021, Frontiers in Immunology.

[18]  E. Lemichez,et al.  Adaptation of Staphylococcus aureus in a Medium Mimicking a Diabetic Foot Environment , 2021, Toxins.

[19]  Jung-Kul Lee,et al.  Polyhydroxyalkanoates: Trends and advances toward biotechnological applications. , 2021, Bioresource technology.

[20]  G. Maisetta,et al.  Therapeutic Potential of Antimicrobial Peptides in Polymicrobial Biofilm-Associated Infections , 2021, International journal of molecular sciences.

[21]  B. Barrois,et al.  Update on the role of antiseptics in the management of chronic wounds with critical colonisation and/or biofilm , 2020, International wound journal.

[22]  L. Cellini,et al.  Graphene Oxide affects Staphylococcus aureus and Pseudomonas aeruginosa dual species biofilm in Lubbock Chronic Wound Biofilm model , 2020, Scientific Reports.

[23]  G. Maisetta,et al.  Editorial: Interspecies Interactions: Effects on Virulence and Antimicrobial Susceptibility of Bacterial and Fungal Pathogens , 2020, Frontiers in Microbiology.

[24]  L. Cellini,et al.  Hop Extract: An Efficacious Antimicrobial and Anti-biofilm Agent Against Multidrug-Resistant Staphylococci Strains and Cutibacterium acnes , 2020, Frontiers in Microbiology.

[25]  K. Rumbaugh,et al.  Differential Efficacy of Glycoside Hydrolases to Disperse Biofilms , 2020, Frontiers in Cellular and Infection Microbiology.

[26]  A. Azad,et al.  Antibacterial activity of graphene oxide nanosheet against multidrug resistant superbugs isolated from infected patients , 2020, Royal Society Open Science.

[27]  M. Emaneini,et al.  Combinatorial effects of antibiotics and enzymes against dual-species Staphylococcus aureus and Pseudomonas aeruginosa biofilms in the wound-like medium , 2020, PloS one.

[28]  Morteza Abazari,et al.  A Systematic Review on Classification, Identification, and Healing Process of Burn Wound Healing , 2020, The international journal of lower extremity wounds.

[29]  P. Stewart,et al.  The zone model: A conceptual model for understanding the microenvironment of chronic wound infection , 2020, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[30]  T. Bjarnsholt,et al.  Current in vitro biofilm-infected chronic wound models for developing new treatment possibilities. , 2020, Advances in wound care.

[31]  J. Rembe,et al.  Efficacy of antiseptics in a novel 3-dimensional human plasma biofilm model (hpBIOM) , 2020, Scientific Reports.

[32]  E. Owusu-Dabo,et al.  Spectrum of antibiotic resistant bacteria and fungi isolated from chronically infected wounds in a rural district hospital in Ghana , 2020, PloS one.

[33]  A. Holmes,et al.  Platelet‐derived transforming growth factor‐β1 promotes keratinocyte proliferation in cutaneous wound healing , 2020, Journal of tissue engineering and regenerative medicine.

[34]  D. Andes,et al.  Contributions of the Biofilm Matrix to Candida Pathogenesis , 2020, Journal of fungi.

[35]  H. Eide,et al.  Pain in persons with chronic venous leg ulcers: A systematic review and meta‐analysis , 2020, International wound journal.

[36]  C. Whitchurch,et al.  Honey can inhibit and eliminate biofilms produced by Pseudomonas aeruginosa , 2019, Scientific Reports.

[37]  Xiaomei Zhu,et al.  Chronic wound biofilms: diagnosis and therapeutic strategies , 2019, Chinese medical journal.

[38]  T. Phillips,et al.  Pressure Ulcers: Pathophysiology, Epidemiology, Risk Factors, and Presentation. , 2019, Journal of the American Academy of Dermatology.

[39]  H. Sanada,et al.  Effectiveness of biofilm‐based wound care system on wound healing in chronic wounds , 2019, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[40]  W. Arnold,et al.  Impact of probiotics on pathogen survival in an innovative human plasma biofilm model (hpBIOM) , 2019, Journal of Translational Medicine.

[41]  L. Cañedo-Dorantes,et al.  Skin Acute Wound Healing: A Comprehensive Review , 2019, International journal of inflammation.

[42]  Yuan-Kun Wu,et al.  Biofilms in Chronic Wounds: Pathogenesis and Diagnosis. , 2019, Trends in biotechnology.

[43]  J. Urbonienė,et al.  New in vitro model evaluating antiseptics’ efficacy in biofilm‐associated Staphylococcus aureus prosthetic vascular graft infection , 2019, Journal of medical microbiology.

[44]  Sanjay K. S. Patel,et al.  Quorum sensing inhibitors as antipathogens: biotechnological applications. , 2019, Biotechnology advances.

[45]  A. Ridiandries,et al.  The Role of Chemokines in Wound Healing , 2018, International journal of molecular sciences.

[46]  D. Tartar,et al.  Immunology of Wound Healing , 2018, Current Dermatology Reports.

[47]  Yie Hou Lee,et al.  An In Vitro Model of Angiogenesis during Wound Healing Provides Insights into the Complex Role of Cells and Factors in the Inflammatory and Proliferation Phase , 2018, International journal of molecular sciences.

[48]  Mingxia Wu,et al.  Distribution of Microbes and Drug Susceptibility in Patients with Diabetic Foot Infections in Southwest China , 2018, Journal of diabetes research.

[49]  K. Brandenburg,et al.  Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds , 2018, Front. Pharmacol..

[50]  V. Velebný,et al.  A porcine model of skin wound infected with a polybacterial biofilm , 2018, Biofouling.

[51]  J. Wilkinson,et al.  Efficacy of hyperbaric oxygen therapy in bacterial biofilm eradication. , 2018, Journal of wound care.

[52]  I. Demarchi,et al.  Contribution of photodynamic therapy in wound healing: A systematic review. , 2017, Photodiagnosis and photodynamic therapy.

[53]  A. Rinaldi,et al.  The Semi-Synthetic Peptide Lin-SB056-1 in Combination with EDTA Exerts Strong Antimicrobial and Antibiofilm Activity against Pseudomonas aeruginosa in Conditions Mimicking Cystic Fibrosis Sputum , 2017, International journal of molecular sciences.

[54]  G. James,et al.  Consensus guidelines for the identification and treatment of biofilms in chronic nonhealing wounds , 2017, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[55]  K. Rumbaugh,et al.  Albumin Inhibits Pseudomonas aeruginosa Quorum Sensing and Alters Polymicrobial Interactions , 2017, Infection and Immunity.

[56]  T. Mah,et al.  Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. , 2017, FEMS microbiology reviews.

[57]  H. Goossens,et al.  In vivo and In vitro Interactions between Pseudomonas aeruginosa and Staphylococcus spp. , 2017, Front. Cell. Infect. Microbiol..

[58]  O. Franco,et al.  Bacterial Contribution in Chronicity of Wounds , 2017, Microbial Ecology.

[59]  R. Ceilley,et al.  Chronic Wound Healing: A Review of Current Management and Treatments , 2017, Advances in Therapy.

[60]  G. James,et al.  The prevalence of biofilms in chronic wounds: a systematic review and meta-analysis of published data. , 2017, Journal of wound care.

[61]  H. Sorg,et al.  Skin Wound Healing: An Update on the Current Knowledge and Concepts , 2016, European Surgical Research.

[62]  Asad Ullah,et al.  Antimicrobial resistance among aerobic biofilm producing bacteria isolated from chronic wounds in the tertiary care hospitals of Peshawar, Pakistan. , 2016, Journal of wound care.

[63]  M. Sojka,et al.  Antibiofilm efficacy of honey and bee-derived defensin-1 on multispecies wound biofilm. , 2016, Journal of medical microbiology.

[64]  T. Wood,et al.  Combatting bacterial infections by killing persister cells with mitomycin C. , 2015, Environmental microbiology.

[65]  R. Manikam,et al.  Prevalence and antibiotic susceptibility of bacteria from acute and chronic wounds in Malaysian subjects. , 2015, Journal of infection in developing countries.

[66]  C. Edmiston,et al.  Approach to chronic wound infections , 2015, The British journal of dermatology.

[67]  R. Serra,et al.  Chronic wound infections: the role of Pseudomonas aeruginosa and Staphylococcus aureus , 2015, Expert review of anti-infective therapy.

[68]  L. Cellini,et al.  Bacterial isolates from infected wounds and their antibiotic susceptibility pattern: some remarks about wound infection , 2015, International wound journal.

[69]  B. Conlon,et al.  Staphylococcus aureus chronic and relapsing infections: Evidence of a role for persister cells , 2014, BioEssays : news and reviews in molecular, cellular and developmental biology.

[70]  K. Rumbaugh,et al.  Synergistic Interactions of Pseudomonas aeruginosa and Staphylococcus aureus in an In Vitro Wound Model , 2014, Infection and Immunity.

[71]  A. Richmond,et al.  Chemokine Regulation of Neutrophil Infiltration of Skin Wounds. , 2014, Advances in wound care.

[72]  V. Velebný,et al.  Multispecies biofilm in an artificial wound bed--A novel model for in vitro assessment of solid antimicrobial dressings. , 2014, Journal of microbiological methods.

[73]  A. Bahar,et al.  Antimicrobial Peptides , 2013, Pharmaceuticals.

[74]  Sashwati Roy,et al.  Neutrophil activity in chronic venous leg ulcers—A target for therapy? , 2013, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[75]  K. Anderson,et al.  Factors That Impair Wound Healing. , 2012, The journal of the American College of Clinical Wound Specialists.

[76]  C. Attinger,et al.  Clinically Addressing Biofilm in Chronic Wounds. , 2012, Advances in wound care.

[77]  S. Dowd,et al.  An In Vivo Polymicrobial Biofilm Wound Infection Model to Study Interspecies Interactions , 2011, PloS one.

[78]  J. Olerud,et al.  Delayed wound healing in diabetic (db/db) mice with Pseudomonas aeruginosa biofilm challenge: a model for the study of chronic wounds , 2010, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[79]  S. Dowd,et al.  Effects of biofilm treatments on the multi-species Lubbock chronic wound biofilm model. , 2009, Journal of wound care.

[80]  Benjamin A Lipsky,et al.  Topical antimicrobial therapy for treating chronic wounds. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[81]  S. Dowd,et al.  Propagation of anaerobic bacteria within an aerobic multi-species chronic wound biofilm model. , 2009, Journal of wound care.

[82]  Yan Sun,et al.  In vitro multispecies Lubbock chronic wound biofilm model , 2008, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[83]  T. Tolker-Nielsen,et al.  Distribution, Organization, and Ecology of Bacteria in Chronic Wounds , 2008, Journal of Clinical Microbiology.

[84]  K. Krogfelt,et al.  Multiple bacterial species reside in chronic wounds: a longitudinal study , 2006, International wound journal.

[85]  D. Allison,et al.  The Biofilm Matrix , 2003, Biofouling.

[86]  Y. Singh,et al.  Quorum Sensing Inhibition: A Target for Treating Chronic Wounds , 2018 .

[87]  S. Cox,et al.  Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing , 2016, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[88]  S. Dowd,et al.  Survey of fungi and yeast in polymicrobial infections in chronic wounds. , 2011, Journal of wound care.

[89]  David W Williams,et al.  Antimicrobial tolerance and the significance of persister cells in recalcitrant chronic wound biofilms , 2011, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[90]  J. Ravel,et al.  Macroscale spatial variation in chronic wound microbiota: A cross‐sectional study , 2011, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[91]  P. Stewart,et al.  Biofilms in chronic wounds , 2008, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.