{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:13:32Z","timestamp":1789658012547,"version":"4.0.1"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,2,16]],"date-time":"2018-02-16T00:00:00Z","timestamp":1518739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["16-27726A"],"award-info":[{"award-number":["16-27726A"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002969","name":"Technologick\u00e1 agentura \u010cesk\u00e9 republiky","doi-asserted-by":"publisher","award":["TA04010638"],"award-info":[{"award-number":["TA04010638"]}],"id":[{"id":"10.13039\/501100002969","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010099","name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences","doi-asserted-by":"publisher","award":["RVO61388963"],"award-info":[{"award-number":["RVO61388963"]}],"id":[{"id":"10.13039\/501100010099","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Hospital in Motol","award":["9777 Advanced therapies"],"award-info":[{"award-number":["9777 Advanced therapies"]}]},{"name":"University Hospital in Motol","award":["6010"],"award-info":[{"award-number":["6010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>We examined the benefits of short linear \u03b1-helical antimicrobial peptides (AMPs) invented in our laboratory for treating bone infection and preventing microbial biofilm formation on model implants due to causative microorganisms of osteomyelitis. For this purpose, we introduced a model of induced osteomyelitis that utilizes human femur heads obtained from the hospital after their replacement with artificial prostheses. We found that the focus of the infection set up in the spongy part of this bone treated with AMP-loaded calcium phosphate cement was eradicated much more effectively than was the focus treated with antibiotics such as vancomycin or gentamicin loaded into the same cement. This contradicts the minimum inhibitory concentrations (MIC) values of AMPs and antibiotics against some bacterial strains obtained in standard in vitro assays. The formation of microbial biofilm on implants made from poly(methylmethacrylate)-based bone cement loaded with AMP was evaluated after the implants\u2019 removal from the infected bone sample. AMPs loaded in such model implants prevented microbial adhesion and subsequent formation of bacterial biofilm on their surface. Biofilms did form, on the other hand, on control implants made from the plain cement when these were implanted into the same infected bone sample. These results of the experiments performed in human bone tissue highlight the clinical potential of antimicrobial peptides for use in treating and preventing osteomyelitis caused by resistant pathogens.<\/jats:p>","DOI":"10.3390\/ph11010020","type":"journal-article","created":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T03:54:22Z","timestamp":1519098862000},"page":"20","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Antimicrobial Peptides for Topical Treatment of Osteomyelitis and Implant-Related Infections: Study in the Spongy Bone"],"prefix":"10.3390","volume":"11","author":[{"given":"Pavel","family":"Melicher\u010d\u00edk","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, First Faculty of Medicine, Charles University in Prague and University Hospital in Motol, V \u00davalu 84, 150 06 Prague 5, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5799-4849","authenticated-orcid":false,"given":"Ond\u0159ej","family":"Ne\u0161uta","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo n\u00e1m. 2, 166 10 Prague 6, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4184-2848","authenticated-orcid":false,"given":"V\u00e1clav","family":"\u010ce\u0159ovsk\u00fd","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo n\u00e1m. 2, 166 10 Prague 6, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jor.2016.10.004","article-title":"Osteomyelitis: Recent advances in pathophysiology and therapeutic strategies","volume":"14","author":"Birt","year":"2017","journal-title":"J. Orthop."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.biotechadv.2016.09.005","article-title":"Understanding osteomyelitis and its treatment through local drug delivery system","volume":"34","author":"Nandi","year":"2016","journal-title":"Biotechnol. Adv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1053\/j.oto.2016.01.002","article-title":"Treatment of chronic bone infection","volume":"26","author":"Winkler","year":"2016","journal-title":"Oper. Tech. Orthop."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/01.blo.0000175122.50804.ce","article-title":"Local antibiotic delivery systems: Where are we and where are we going?","volume":"437","author":"Hanssen","year":"2005","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1007\/s11999-008-0245-0","article-title":"Daptomycin eluted from calcium sulfate appears effective against Staphylococcus","volume":"466","author":"Webb","year":"2008","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.diagmicrobio.2013.09.014","article-title":"Elution kinetics, antimicrobial activity, and mechanical properties of 11 different antibiotic loaded acrylic bone cement","volume":"78","author":"Moliz","year":"2014","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s13346-011-0015-5","article-title":"The use of bone cement for the localized, controlled release of the antibiotics vancomycin, linezolid, or fusidic acid: Effect of additives on drug release rates and mechanical strength","volume":"1","author":"Jackson","year":"2011","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1302\/0301-620X.89B7.19148","article-title":"The role of polymethylmethacrylate bone cement in modern orthopaedic surgery","volume":"89","author":"Webb","year":"2007","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/jac\/dki435","article-title":"Daptomycin treatment of Staphylococcus aureus experimental chronic osteomyelitis","volume":"57","author":"Rouse","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6363","DOI":"10.1016\/j.biomaterials.2010.05.005","article-title":"Antibiotic-loaded biomaterials and the risks for the spread of antibiotic resistance following their prophylactic and therapeutic clinical use","volume":"31","author":"Campoccia","year":"2010","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-3-319-11038-7_2","article-title":"Biofilm-based implant infections in orthopaedics","volume":"830","author":"Arciola","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1179\/1973947812Y.0000000045","article-title":"Antibiofilm agents and implant-related infections in orthopaedics: Where are we?","volume":"25","author":"Romano","year":"2013","journal-title":"J. Chemother."},{"key":"ref_13","first-page":"176","article-title":"Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions","volume":"2","author":"Ribeiro","year":"2012","journal-title":"Biomaterials"},{"key":"ref_14","first-page":"217","article-title":"Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals?","volume":"38","author":"Brogden","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_15","first-page":"228","article-title":"Antimicrobial peptides\u2014Promising alternatives to conventional antibiotics","volume":"20","author":"Baltzer","year":"2011","journal-title":"J. Mol. Microbiol. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cbpa.2017.03.014","article-title":"Host defense antimicrobial peptides as antibiotics: Design and application strategies","volume":"38","author":"Mishra","year":"2017","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1124\/pr.55.1.2","article-title":"Mechanisms of antimicrobial peptide action and resistance","volume":"55","author":"Yeaman","year":"2003","journal-title":"Pharmacol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tibtech.2011.05.001","article-title":"The expanding scope of antimicrobial peptide structures and their modes of action","volume":"29","author":"Nguyen","year":"2011","journal-title":"Trends Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R14","DOI":"10.1016\/j.cub.2015.11.017","article-title":"Antimicrobial peptides","volume":"26","author":"Zhang","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mishra, B., and Wang, G. (2017). Individual and combined effects of engineered peptides and antibiotics on Pseudomonas aeruginosa biofilms. Pharmaceuticals, 10.","DOI":"10.3390\/ph10030058"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1093\/jac\/dkg258","article-title":"Release of antimicrobial peptide Dhvar-5 from polymethylmethacrylate beads","volume":"51","author":"Faber","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1093\/jac\/dkh346","article-title":"Osteomyelitis prevention in rabbits using antimicrobial peptide hLF1-11- or gentamicin-containing calcium phosphate cement","volume":"54","author":"Stallmann","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1093\/jac\/dkh441","article-title":"In vivo comparison of Dhvar-5 and gentamicin in MRSA osteomyelitis prevention model","volume":"54","author":"Faber","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1128\/AAC.49.6.2438-2444.2005","article-title":"Comparable efficacies of the antimicrobial peptide human lactoferrin 1-11 and gentamicin in a chronic methicillin-resistant Staphylococcus aureus osteomyelitis model","volume":"49","author":"Faber","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4919","DOI":"10.1128\/AAC.48.12.4919-4921.2004","article-title":"The synthetic N-terminal peptide of human lactoferin, hLF(1-11), is highly effective against experimental infection caused by multidrug-resistant Acinetobacter baumannii","volume":"48","author":"Dijkshoorn","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2015.12.003","article-title":"Prevention of Staphylococcus aureus biomaterial-associated infections using a polymer-lipid coating containing the antimicrobial peptide OP-145","volume":"222","author":"Riool","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1002\/jbm.a.34132","article-title":"Antimicrobial peptide incorporated poly(2-hydroxyethyl methacrylate) hydrogels for the prevention of Staphylococcus epidermidis-associated biomaterial infections","volume":"100A","author":"Laverty","year":"2012","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/cbic.200900133","article-title":"Lasioglossins: Three novel antimicrobial peptides from the venom of the eusocial bee Lasioglossum laticeps (Hymenoptera: Halictidae)","volume":"10","author":"Hovorka","year":"2009","journal-title":"ChemBioChem"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00726-010-0519-1","article-title":"Novel antimicrobial peptides from the venom of the eusocial bee Halictus sexcinctus (Hymenoptera: Halictidae) and their analogs","volume":"39","author":"Hovorka","year":"2010","journal-title":"Amino Acids"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"D933","DOI":"10.1093\/nar\/gkn823","article-title":"APD2: The updated antimicrobial peptide database and its application in peptide design","volume":"37","author":"Wang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_31","first-page":"ftx091","article-title":"How proteases from Enterococcus faecalis contribute to its resistance to short \u03b1-helical antimicrobial peptides","volume":"75","year":"2017","journal-title":"Pathog. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1399-3011.2004.00179.x","article-title":"Synthesis and characterization of human \u03b1-defensins 4-6","volume":"64","author":"Wu","year":"2004","journal-title":"J. Pept. Res."},{"key":"ref_33","unstructured":"Anderson, R.J., Groundwater, P.W., Todd, A., and Worsley, A.J. (2012). Antibacterial Agents: Chemistry, Mode of Action, Mechanism of Resistance and Clinical Applications, John Wiley & Sons, Ltd.. [1st ed.]. Chapters 5.2.4\u20135.2.6."},{"key":"ref_34","unstructured":"Anderson, R.J., Groundwater, P.W., Todd, A., and Worsley, A.J. (2012). Antibacterial Agents: Chemistry, Mode of Action, Mechanism of Resistance and Clinical Applications, John Wiley & Sons, Ltd.. [1st ed.]. Chapters 4.1.4\u20134.1.6."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12223-017-0540-9","article-title":"Testing the efficacy of antimicrobial peptides in the topical treatment of induced osteomyelitis in rats","volume":"63","author":"Jahoda","year":"2018","journal-title":"Folia Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jbspin.2014.02.013","article-title":"Bone marrow fat","volume":"81","author":"Hardouin","year":"2014","journal-title":"Jt. Bone Spine"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/11\/1\/20\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:55:22Z","timestamp":1760194522000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/11\/1\/20"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,16]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["ph11010020"],"URL":"https:\/\/doi.org\/10.3390\/ph11010020","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,16]]}}}