{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:50:48Z","timestamp":1790614248842,"version":"4.1.0"},"reference-count":113,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Research Board of Ireland (HRB)","award":["HRBMRCG-2018-01"],"award-info":[{"award-number":["HRBMRCG-2018-01"]}]},{"name":"Health Research Board of Ireland (HRB)","award":["19\/FFP\/6882"],"award-info":[{"award-number":["19\/FFP\/6882"]}]},{"name":"Diabetes Ireland Research Alliance (DIRA)","award":["HRBMRCG-2018-01"],"award-info":[{"award-number":["HRBMRCG-2018-01"]}]},{"name":"Diabetes Ireland Research Alliance (DIRA)","award":["19\/FFP\/6882"],"award-info":[{"award-number":["19\/FFP\/6882"]}]},{"DOI":"10.13039\/100010414","name":"Health Research Charities Ireland (HRCI)","doi-asserted-by":"publisher","award":["HRBMRCG-2018-01"],"award-info":[{"award-number":["HRBMRCG-2018-01"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010414","name":"Health Research Charities Ireland (HRCI)","doi-asserted-by":"publisher","award":["19\/FFP\/6882"],"award-info":[{"award-number":["19\/FFP\/6882"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["HRBMRCG-2018-01"],"award-info":[{"award-number":["HRBMRCG-2018-01"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["19\/FFP\/6882"],"award-info":[{"award-number":["19\/FFP\/6882"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic foot infection (DFI) management requires complex multidisciplinary care pathways with off-loading, debridement and targeted antibiotic treatment central to positive clinical outcomes. Local administration of topical treatments and advanced wound dressings are often used for more superficial infections, and in combination with systemic antibiotics for more advanced infections. In practice, the choice of such topical approaches, whether alone or as adjuncts, is rarely evidence-based, and there does not appear to be a single market leader. There are several reasons for this, including a lack of clear evidence-based guidelines on their efficacy and a paucity of robust clinical trials. Nonetheless, with a growing number of people living with diabetes, preventing the progression of chronic foot infections to amputation is critical. Topical agents may increasingly play a role, especially as they have potential to limit the use of systemic antibiotics in an environment of increasing antibiotic resistance. While a number of advanced dressings are currently marketed for DFI, here we review the literature describing promising future-focused approaches for topical treatment of DFI that may overcome some of the current hurdles. Specifically, we focus on antibiotic-impregnated biomaterials, novel antimicrobial peptides and photodynamic therapy.<\/jats:p>","DOI":"10.3390\/ijms24043913","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T05:37:46Z","timestamp":1676439466000},"page":"3913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Improving the Management and Treatment of Diabetic Foot Infection: Challenges and Research Opportunities"],"prefix":"10.3390","volume":"24","author":[{"given":"Kaja","family":"Turza\u0144ska","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Education and Research Centre, Beaumont Hospital, D09 YD60 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwafolajimi","family":"Adesanya","sequence":"additional","affiliation":[{"name":"School of Molecular and Cellular Biology, University of Illinois Urbana-Champaign, Champaign, IL 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwene","family":"Rajagopal","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Education and Research Centre, Beaumont Hospital, D09 YD60 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary T.","family":"Pryce","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, Dublin City University, D09 V209 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-3839","authenticated-orcid":false,"given":"Deirdre","family":"Fitzgerald Hughes","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Education and Research Centre, Beaumont Hospital, D09 YD60 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Foundation (IDF) (2022, September 29). IDF Diabetes Atlas|Tenth Edition. Available online: https:\/\/diabetesatlas.org\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1080\/07853890.2016.1231932","article-title":"Global Epidemiology of Diabetic Foot Ulceration: A Systematic Review and Meta-Analysis\u2020","volume":"49","author":"Zhang","year":"2017","journal-title":"Ann. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.12968\/jowc.2019.28.Sup1.S4","article-title":"Risk Factor Analysis on the Healing Time and Infection Rate of Diabetic Foot Ulcers in a Referral Wound Care Clinic","volume":"28","author":"Kee","year":"2019","journal-title":"J. Wound Care"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jia, L., Parker, C.N., Parker, T.J., Kinnear, E.M., Derhy, P.H., Alvarado, A.M., Huygens, F., and Lazzarini, P.A. (2017). Diabetic Foot Working Group, Queensland Statewide Diabetes Clinical Network (Australia) Incidence and Risk Factors for Developing Infection in Patients Presenting with Uninfected Diabetic Foot Ulcers. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177916"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1053\/j.jfas.2017.06.004","article-title":"Predictors of Lower Extremity Amputation and Reamputation Associated With the Diabetic Foot","volume":"56","author":"Acar","year":"2017","journal-title":"J. Foot Ankle Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/dme.13537","article-title":"Prognosis of the Infected Diabetic Foot Ulcer: A 12-Month Prospective Observational Study","volume":"35","author":"Ndosi","year":"2018","journal-title":"Diabet. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1002\/1520-7560(200009\/10)16:1+<::AID-DMRR139>3.0.CO;2-8","article-title":"What Is the Most Effective Way to Reduce Incidence of Amputation in the Diabetic Foot?","volume":"16","author":"Apelqvist","year":"2000","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_8","first-page":"371938","article-title":"Does the Diabetic Foot Have a Significant Impact on Selected Psychological or Social Characteristics of Patients with Diabetes Mellitus?","volume":"2014","author":"Game","year":"2014","journal-title":"J. Diabetes Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1111\/iwj.13348","article-title":"Depression in Diabetic Foot Ulcer: Associated Factors and the Impact of Perceived Social Support and Anxiety on Depression","volume":"17","author":"Polikandrioti","year":"2020","journal-title":"Int. Wound J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107960","DOI":"10.1016\/j.jdiacomp.2021.107960","article-title":"Patient Perspectives on the Physical, Psycho-Social, and Financial Impacts of Diabetic Foot Ulceration and Amputation","volume":"35","author":"Crocker","year":"2021","journal-title":"J. Diabetes Complicat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.4239\/wjd.v2.i2.24","article-title":"New Insights in Diabetic Foot Infection","volume":"2","author":"Richard","year":"2011","journal-title":"World J. Diabetes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.clinbiomech.2013.08.004","article-title":"Biomechanical Characteristics of Peripheral Diabetic Neuropathy: A Systematic Review and Meta-Analysis of Findings from the Gait Cycle, Muscle Activity and Dynamic Barefoot Plantar Pressure","volume":"28","author":"Fernando","year":"2013","journal-title":"Clin. Biomech."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1161\/CIRCULATIONAHA.108.191170","article-title":"American Heart Association Atherosclerotic Peripheral Vascular Disease Symposium II: Executive Summary","volume":"118","author":"Creager","year":"2008","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1161\/01.CIR.88.3.837","article-title":"Ankle-Arm Index as a Marker of Atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group","volume":"88","author":"Newman","year":"1993","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1007\/s00134-002-1628-4","article-title":"High Glucose Impairs Superoxide Production from Isolated Blood Neutrophils","volume":"29","author":"Perner","year":"2003","journal-title":"Intensive Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1080\/15476910802604564","article-title":"Effects of Diabetes Mellitus vs. in Vitro Hyperglycemia on Select Immune Cell Functions","volume":"6","author":"Daoud","year":"2009","journal-title":"J. Immunotoxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"648.11","DOI":"10.1096\/fasebj.27.1_supplement.648.11","article-title":"Severe Hyperglycemia Down Regulates Toll-Like Receptors on Neutrophils: Implications for Propensity to Infections in Diabetics","volume":"27","author":"Jialal","year":"2013","journal-title":"FASEB J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/0973-3930.50707","article-title":"Implementation of Diabetic Foot Ulcer Classification System for Research Purposes to Predict Lower Extremity Amputation","volume":"29","author":"Widatalla","year":"2009","journal-title":"Int. J. Diabetes Dev. Ctries"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S90","DOI":"10.1002\/dmrr.464","article-title":"Diabetic Foot Ulcer Classification System for Research Purposes: A Progress Report on Criteria for Including Patients in Research Studies","volume":"20","author":"Schaper","year":"2004","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chuan, F., Tang, K., Jiang, P., Zhou, B., and He, X. (2015). Reliability and Validity of the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) Classification System and Score in Patients with Diabetic Foot Ulcer. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124739"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Eschler, A., Gradl, G., Wussow, A., and Mittlmeier, T. (2015). Prediction of Complications in a High-Risk Cohort of Patients Undergoing Corrective Arthrodesis of Late Stage Charcot Deformity Based on the PEDIS Score. BMC Musculoskelet. Disord., 16.","DOI":"10.1186\/s12891-015-0809-6"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.jvs.2014.11.045","article-title":"The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System Based on Wound, Ischemia, and Foot Infection (WIfI) Correlates with Risk of Major Amputation and Time to Wound Healing","volume":"61","author":"Zhan","year":"2015","journal-title":"J. Vasc. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e3280","DOI":"10.1002\/dmrr.3280","article-title":"Guidelines on the Diagnosis and Treatment of Foot Infection in Persons with Diabetes (IWGDF 2019 Update)","volume":"36","author":"Lipsky","year":"2020","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S83","DOI":"10.1086\/383267","article-title":"Diagnosing Foot Infection in Diabetes","volume":"39","author":"Williams","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"936","DOI":"10.2337\/dc16-2189","article-title":"Health Care Service and Outcomes Among an Estimated 6.7 Million Ambulatory Care Diabetic Foot Cases in the U.S","volume":"40","author":"Skrepnek","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e132","DOI":"10.1093\/cid\/cis346","article-title":"2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections","volume":"54","author":"Lipsky","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ijid.2017.04.012","article-title":"Are Antibiotic-Resistant Pathogens More Common in Subsequent Episodes of Diabetic Foot Infection?","volume":"59","author":"Lebowitz","year":"2017","journal-title":"Int. J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ijid.2015.09.023","article-title":"Diabetic Foot Infections: What Have We Learned in the Last 30 Years?","volume":"40","author":"Lew","year":"2015","journal-title":"Int. J. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1097\/00006534-199504001-00015","article-title":"Quantitative Culture Technique and Infection in Complex Wounds of the Extremities Closed with Free Flaps","volume":"95","author":"Breidenbach","year":"1995","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.suc.2020.05.007","article-title":"Bacteria and Antibiotics in Wound Healing","volume":"100","author":"Caldwell","year":"2020","journal-title":"Surg. Clin. N. Am."},{"key":"ref_31","first-page":"23","article-title":"Infection in Chronic Wounds: Controversies in Diagnosis and Treatment","volume":"45","author":"Dow","year":"1999","journal-title":"Ostomy Wound Manag."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"H\u00f8gsberg, T., Bjarnsholt, T., Thomsen, J.S., and Kirketerp-M\u00f8ller, K. (2011). Success Rate of Split-Thickness Skin Grafting of Chronic Venous Leg Ulcers Depends on the Presence of Pseudomonas Aeruginosa: A Retrospective Study. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020492"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"378","DOI":"10.2337\/dc06-1383","article-title":"Bacterial Load Predicts Healing Rate in Neuropathic Diabetic Foot Ulcers","volume":"30","author":"Xu","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.12968\/jowc.2016.25.Sup9.S11","article-title":"Clinical Investigation of Biofilm in Non-Healing Wounds by High Resolution Microscopy Techniques","volume":"25","author":"Hurlow","year":"2016","journal-title":"J. Wound Care"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.tim.2014.02.001","article-title":"Molecular Mechanisms of Antimicrobial Tolerance and Resistance in Bacterial and Fungal Biofilms","volume":"22","author":"Coenye","year":"2014","journal-title":"Trends Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nrmicro.2016.94","article-title":"Biofilms: An Emergent Form of Bacterial Life","volume":"14","author":"Flemming","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e3266","DOI":"10.1002\/dmrr.3266","article-title":"Practical Guidelines on the Prevention and Management of Diabetic Foot Disease (IWGDF 2019 Update)","volume":"36","author":"Schaper","year":"2020","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lipsky, B.A., and U\u00e7kay, \u0130. (2021). Treating Diabetic Foot Osteomyelitis: A Practical State-of-the-Art Update. Medicina, 57.","DOI":"10.3390\/medicina57040339"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.12968\/jowc.2013.22.Sup5.S1","article-title":"EWMA Document: Antimicrobials and Non-Healing Wounds. Evidence, Controversies and Suggestions","volume":"22","author":"Gottrup","year":"2013","journal-title":"J. Wound Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/dmrr.2699","article-title":"IWGDF Guidance on the Diagnosis and Management of Foot Infections in Persons with Diabetes","volume":"32","author":"Lipsky","year":"2016","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_41","first-page":"CD011038","article-title":"Topical Antimicrobial Agents for Treating Foot Ulcers in People with Diabetes","volume":"6","author":"Dumville","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_42","first-page":"1","article-title":"Systematic Reviews of Wound Care Management: (3) Antimicrobial Agents for Chronic Wounds; (4) Diabetic Foot Ulceration","volume":"4","author":"Cullum","year":"2000","journal-title":"Health Technol. Assess."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1302\/0301-620X.100B11.BJJ-2018-0720","article-title":"A Systematic Review of Local Antibiotic Devices Used to Improve Wound Healing Following the Surgical Management of Foot Infections in Diabetics","volume":"100-B","author":"Marson","year":"2018","journal-title":"Bone Jt. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/dmrr.2706","article-title":"Interventions in the Management of Infection in the Foot in Diabetes: A Systematic Review","volume":"32","author":"Peters","year":"2016","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1177\/1534734618757532","article-title":"Local Antibiotic Delivery Systems: Current and Future Applications for Diabetic Foot Infections","volume":"17","author":"Markakis","year":"2018","journal-title":"Int. J. Low. Extrem Wounds"},{"key":"ref_46","first-page":"S19","article-title":"Management of Chronic Wounds: Diagnosis, Preparation, Treatment, and Follow-Up","volume":"29","author":"Gupta","year":"2017","journal-title":"Wounds"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"232","DOI":"10.12968\/jowc.2011.20.5.232","article-title":"Molecular Diagnostics and Personalised Medicine in Wound Care: Assessment of Outcomes","volume":"20","author":"Dowd","year":"2011","journal-title":"J. Wound Care"},{"key":"ref_48","first-page":"CD009099","article-title":"Hydrocolloid Dressings for Healing Diabetic Foot Ulcers","volume":"8","author":"Dumville","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_49","first-page":"CD009110","article-title":"Alginate Dressings for Healing Diabetic Foot Ulcers","volume":"6","author":"Dumville","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"546","DOI":"10.4239\/wjd.v5.i4.546","article-title":"Choice of Wound Care in Diabetic Foot Ulcer: A Practical Approach","volume":"5","author":"Kavitha","year":"2014","journal-title":"World J. Diabetes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3389\/fbioe.2020.00516","article-title":"Functional Biomaterials for Treatment of Chronic Wound","volume":"8","author":"Zhang","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1016\/j.actbio.2011.04.003","article-title":"A PEGylated Fibrin-Based Wound Dressing with Antimicrobial and Angiogenic Activity","volume":"7","author":"Seetharaman","year":"2011","journal-title":"Acta Biomater."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/iwj.12791","article-title":"A PEGylated Fibrin Hydrogel-based Antimicrobial Wound Dressing Controls Infection without Impeding Wound Healing","volume":"14","author":"Gil","year":"2017","journal-title":"Int. Wound J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.msec.2015.11.036","article-title":"Anti-Biofilm Activity of Chitosan Gels Formulated with Silver Nanoparticles and Their Cytotoxic Effect on Human Fibroblasts","volume":"60","author":"Velasquillo","year":"2016","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2337\/dc06-1792","article-title":"Use of Tobramycin-Impregnated Calcium Sulphate Pellets in Addition to Oral Antibiotics: An Alternative Treatment to Minor Amputation in a Case of Diabetic Foot Osteomyelitis","volume":"30","author":"Salgami","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"259","DOI":"10.7547\/1010259","article-title":"Management in the Wound-Care Center Outpatient Setting of a Diabetic Patient with Forefoot Osteomyelitis Using Cerament Bone Void Filler Impregnated with Vancomycin: Off-Label Use","volume":"101","author":"Karr","year":"2011","journal-title":"J. Am. Podiatr. Med. Assoc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.foot.2015.07.002","article-title":"Calcium Sulphate as a Drug Delivery System in a Deep Diabetic Foot Infection","volume":"27","author":"Morley","year":"2016","journal-title":"Foot"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Price, B.L., Morley, R., Bowling, F.L., Lovering, A.M., and Dobson, C.B. (2020). Susceptibility of Monomicrobial or Polymicrobial Biofilms Derived from Infected Diabetic Foot Ulcers to Topical or Systemic Antibiotics in Vitro. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0228704"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1128\/AAC.40.12.2675","article-title":"Antibiotic-Impregnated Cement and Beads for Orthopedic Infections","volume":"40","author":"Wininger","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/00003086-198604000-00021","article-title":"Gentamicin-PMMA Beads. Pharmacokinetic and Nephrotoxicological Study","volume":"205","author":"Walenkamp","year":"1986","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1007\/s00253-015-6375-x","article-title":"Antimicrobial Peptides: An Alternative for Innovative Medicines?","volume":"99","author":"Cova","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1039\/D1CS90109E","article-title":"Correction: The Multifaceted Nature of Antimicrobial Peptides: Current Synthetic Chemistry Approaches and Future Directions","volume":"51","author":"Gan","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.actbio.2019.12.025","article-title":"Topical Antimicrobial Peptide Formulations for Wound Healing: Current Developments and Future Prospects","volume":"103","author":"Thapa","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/sj.jid.5700599","article-title":"Antimicrobial Peptides Human Beta-Defensins Stimulate Epidermal Keratinocyte Migration, Proliferation and Production of Proinflammatory Cytokines and Chemokines","volume":"127","author":"Niyonsaba","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Gonzalez-Curiel, I., Trujillo, V., Montoya-Rosales, A., Rincon, K., Rivas-Calderon, B., deHaro-Acosta, J., Marin-Luevano, P., Lozano-Lopez, D., Enciso-Moreno, J.A., and Rivas-Santiago, B. (2014). 1,25-Dihydroxyvitamin D3 Induces LL-37 and HBD-2 Production in Keratinocytes from Diabetic Foot Ulcers Promoting Wound Healing: An in Vitro Model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111355"},{"key":"ref_66","first-page":"20","article-title":"Chitosan Hydrogel Encapsulated with LL-37 Peptide Promotes Deep Tissue Injury Healing in a Mouse Model","volume":"7","author":"Yang","year":"2020","journal-title":"Mil. Med. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/j.peptides.2005.03.009","article-title":"In Vitro Activity of Amphibian Peptides Alone and in Combination with Antimicrobial Agents against Multidrug-Resistant Pathogens Isolated from Surgical Wound Infection","volume":"26","author":"Giacometti","year":"2005","journal-title":"Peptides"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1111\/febs.12968","article-title":"A Short Peptide from Frog Skin Accelerates Diabetic Wound Healing","volume":"281","author":"Liu","year":"2014","journal-title":"FEBS J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3874","DOI":"10.1111\/febs.14940","article-title":"Inhibition of Pseudomonas Aeruginosa Biofilm Formation and Expression of Virulence Genes by Selective Epimerization in the Peptide Esculentin-1a(1\u201321)NH2","volume":"286","author":"Casciaro","year":"2019","journal-title":"FEBS J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1086\/593185","article-title":"Topical versus Systemic Antimicrobial Therapy for Treating Mildly Infected Diabetic Foot Ulcers: A Randomized, Controlled, Double-Blinded, Multicenter Trial of Pexiganan Cream","volume":"47","author":"Lipsky","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1016\/j.bbamem.2008.10.009","article-title":"Structure, Membrane Orientation, Mechanism, and Function of Pexiganan\u2014A Highly Potent Antimicrobial Peptide Designed from Magainin","volume":"1788","author":"Gottler","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.actbio.2016.12.047","article-title":"Collagen Tethering of Synthetic Human Antimicrobial Peptides Cathelicidin LL37 and Its Effects on Antimicrobial Activity and Cytotoxicity","volume":"52","author":"Lozeau","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.actbio.2016.09.041","article-title":"Gold-Nanoparticles Coated with the Antimicrobial Peptide Esculentin-1a(1\u201321)NH2 as a Reliable Strategy for Antipseudomonal Drugs","volume":"47","author":"Casciaro","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.biortech.2004.08.012","article-title":"Microbial Synthesis of Poly(Epsilon-Lysine) and Its Various Applications","volume":"97","author":"Shih","year":"2006","journal-title":"Bioresour. Technol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"15989","DOI":"10.1021\/acsami.9b21683","article-title":"Multifunctional Antimicrobial Nanofiber Dressings Containing \u03b5-Polylysine for the Eradication of Bacterial Bioburden and Promotion of Wound Healing in Critically Colonized Wounds","volume":"12","author":"Mayandi","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"25025","DOI":"10.1021\/acsami.1c23734","article-title":"Star-Peptide Polymers Are Multi-Drug-Resistant Gram-Positive Bacteria Killers","volume":"14","author":"Li","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"16162","DOI":"10.1038\/nmicrobiol.2016.162","article-title":"Combating Multidrug-Resistant Gram-Negative Bacteria with Structurally Nanoengineered Antimicrobial Peptide Polymers","volume":"1","author":"Lam","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e1800627","DOI":"10.1002\/adhm.201800627","article-title":"Architectural Effects of Star-Shaped \u201cStructurally Nanoengineered Antimicrobial Peptide Polymers\u201d (SNAPPs) on Their Biological Activity","volume":"7","author":"Shirbin","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4","DOI":"10.12688\/hrbopenres.13380.1","article-title":"Modified Poly(L-Lysine)-Based Structures as Novel Antimicrobials for Diabetic Foot Infections, an in-Vitro Study","volume":"5","author":"Grace","year":"2022","journal-title":"HRB Open Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"807","DOI":"10.2174\/138161212799277617","article-title":"Therapeutic Potential of Host Defense Peptides in Antibiotic-Resistant Infections","volume":"18","author":"Afacan","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1042\/BCJ20180483","article-title":"Potential Role of a Series of Lysine-\/Leucine-Rich Antimicrobial Peptide in Inhibiting Lipopolysaccharide-Induced Inflammation","volume":"475","author":"Dong","year":"2018","journal-title":"Biochem. J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1039\/C5MD00373C","article-title":"Synergistic Activity of a Short Lipidated Antimicrobial Peptide (LipoAMP) and Colistin or Tobramycin against Pseudomonas Aeruginosa from Cystic Fibrosis Patients","volume":"7","author":"Albada","year":"2016","journal-title":"Med. Chem. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"940","DOI":"10.2174\/0929866522666150728115439","article-title":"In Vitro Synergistic Effect of the CM11 Antimicrobial Peptide in Combination with Common Antibiotics against Clinical Isolates of Six Species of Multidrug-Resistant Pathogenic Bacteria","volume":"22","author":"Amani","year":"2015","journal-title":"Protein Pept. Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1096\/fj.13-227942","article-title":"Sensitization of Gram-Negative Bacteria by Targeting the Membrane Potential","volume":"27","author":"Goldberg","year":"2013","journal-title":"FASEB J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2174\/1568011023354137","article-title":"Porphyrins in Photodynamic Therapy\u2014A Search for Ideal Photosensitizers","volume":"2","author":"Pushpan","year":"2002","journal-title":"Curr. Med. Chem. Anticancer Agents"},{"key":"ref_86","first-page":"21","article-title":"Phototherapy with Light Emitting Diodes: Treating a Broad Range of Medical and Aesthetic Conditions in Dermatology","volume":"11","author":"Ablon","year":"2018","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"799","DOI":"10.17219\/acem\/32488","article-title":"Photodynamic Therapy As a Promising Method Used in the Treatment of Oral Diseases","volume":"25","author":"Mielczarek","year":"2016","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.biopha.2016.07.058","article-title":"The Potential of Photodynamic Therapy (PDT)-Experimental Investigations and Clinical Use","volume":"83","author":"Oniszczuk","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"101828","DOI":"10.1016\/j.pdpdt.2020.101828","article-title":"Methylene Blue Mediated Antimicrobial Photodynamic Therapy in Clinical Human Studies: The State of the Art","volume":"31","author":"Pavani","year":"2020","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.pdpdt.2019.08.012","article-title":"Photodynamic Treatment for Multidrug-Resistant Gram-Negative Bacteria: Perspectives for the Treatment of Klebsiella Pneumoniae Infections","volume":"28","author":"Palavecino","year":"2019","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"159157","DOI":"10.1155\/2013\/159157","article-title":"Antimicrobial Photodynamic Therapy for Methicillin-Resistant Staphylococcus Aureus Infection","volume":"2013","author":"Fu","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/lsm.22045","article-title":"Type I and Type II Mechanisms of Antimicrobial Photodynamic Therapy: An in Vitro Study on Gram-Negative and Gram-Positive Bacteria","volume":"44","author":"Huang","year":"2012","journal-title":"Lasers Surg. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.3389\/fmicb.2018.01299","article-title":"Antimicrobial Photodynamic Therapy to Control Clinically Relevant Biofilm Infections","volume":"9","author":"Hu","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/bjd.12098","article-title":"Phase IIa Randomized, Placebo-Controlled Study of Antimicrobial Photodynamic Therapy in Bacterially Colonized, Chronic Leg Ulcers and Diabetic Foot Ulcers: A New Approach to Antimicrobial Therapy","volume":"168","author":"Morley","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10103-013-1283-8","article-title":"Study of Photodynamic Therapy in the Control of Isolated Microorganisms from Infected Wounds\u2014An in Vitro Study","volume":"29","author":"Khouri","year":"2014","journal-title":"Lasers Med. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/1011-1344(91)80035-G","article-title":"In Vivo Effects of Porphyrins on Bacterial DNA","volume":"11","author":"Nir","year":"1991","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/lsm.21037","article-title":"Photodynamic Therapy Using Intra-Articular Photofrin for Murine MRSA Arthritis: Biphasic Light Dose Response for Neutrophil-Mediated Antibacterial Effect","volume":"43","author":"Tanaka","year":"2011","journal-title":"Lasers Surg. Med."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Zolfaghari, P.S., Packer, S., Singer, M., Nair, S.P., Bennett, J., Street, C., and Wilson, M. (2009). In Vivo Killing of Staphylococcus Aureus Using a Light-Activated Antimicrobial Agent. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-27"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1099\/00222615-42-1-62","article-title":"Killing of Methicillin-Resistant Staphylococcus Aureus by Low-Power Laser Light","volume":"42","author":"Wilson","year":"1995","journal-title":"J. Med. Microbiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1039\/b502125a","article-title":"Photodynamic Therapy for Staphylococcus Aureus Infected Burn Wounds in Mice","volume":"4","author":"Lambrechts","year":"2005","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/lsm.20775","article-title":"Optimization of Topical Photodynamic Therapy with 3,7-Bis(Di-n-Butylamino)Phenothiazin-5-Ium Bromide for Cutaneous Leishmaniasis","volume":"41","author":"Akilov","year":"2009","journal-title":"Lasers Surg. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.pdpdt.2014.04.007","article-title":"A Clinical Trial Testing the Efficacy of PDT in Preventing Amputation in Diabetic Patients","volume":"11","author":"Tardivo","year":"2014","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/cmdc.202000529","article-title":"BODIPY-Based Photosensitizers as Potential Anticancer and Antibacterial Agents: Role of the Positive Charge and the Heavy Atom Effect","volume":"16","author":"Piskorz","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/chem.201904306","article-title":"Spin-Orbit Charge-Transfer Intersystem Crossing (ISC) in Compact Electron Donor-Acceptor Dyads: ISC Mechanism and Application as Novel and Potent Photodynamic Therapy Reagents","volume":"26","author":"Wang","year":"2020","journal-title":"Chemistry"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"7648","DOI":"10.1039\/D1BM01384J","article-title":"Multifunctional BODIPY for Effective Inactivation of Gram-Positive Bacteria and Promotion of Wound Healing","volume":"9","author":"Li","year":"2021","journal-title":"Biomater. Sci."},{"key":"ref_106","first-page":"257","article-title":"Photodynamic Therapy of Extracellular Matrix Stimulates Endothelial Cell Growth by Inactivation of Matrix-Associated Transforming Growth Factor-Beta","volume":"76","author":"Adili","year":"1997","journal-title":"Lab. Investig."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/bjd.12843","article-title":"Topical Photodynamic Therapy Following Excisional Wounding of Human Skin Increases Production of Transforming Growth Factor-\u03923 and Matrix Metalloproteinases 1 and 9, with Associated Improvement in Dermal Matrix Organization","volume":"171","author":"Mills","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e201800318","DOI":"10.1002\/jbio.201800318","article-title":"Amphiphilic Tetracationic Porphyrins Are Exceptionally Active Antimicrobial Photosensitizers: In Vitro and in Vivo Studies with the Free-base and Pd-chelate","volume":"12","author":"Xuan","year":"2019","journal-title":"J. Biophotonics"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"18143","DOI":"10.1021\/acs.jmedchem.1c01643","article-title":"Discovery of Meso- (Meta-Pyridinium) BODIPY Photosensitizers: In Vitro and In Vivo Evaluations for Antimicrobial Photodynamic Therapy","volume":"64","author":"Lin","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Zhao, Z.-J., Xu, Z.-P., Ma, Y.-Y., Ma, J.-D., and Hong, G. (2020). Photodynamic Antimicrobial Chemotherapy in Mice with Pseudomonas Aeruginosa-Infected Wounds. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0237851"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"7796","DOI":"10.1021\/jm1009555","article-title":"Cationic Porphycenes as Potential Photosensitizers for Antimicrobial Photodynamic Therapy","volume":"53","author":"Dai","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4031","DOI":"10.1007\/s00253-015-6539-8","article-title":"Antimicrobial Photodynamic Therapy with Fulleropyrrolidine: Photoinactivation Mechanism of Staphylococcus Aureus, in Vitro and in Vivo Studies","volume":"99","author":"Grinholc","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/lsm.22785","article-title":"The Synergistic Effect of PDT and Oxacillin on Clinical Isolates of Staphylococcus Aureus","volume":"50","author":"Iluz","year":"2018","journal-title":"Lasers Surg. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3913\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:36:30Z","timestamp":1760121390000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3913"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,15]]},"references-count":113,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043913"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043913","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,15]]}}}