{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:26:25Z","timestamp":1790011585588,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant","award":["2022R1A2C1007622"],"award-info":[{"award-number":["2022R1A2C1007622"]}]},{"name":"Soonchunhyang University Research Fund","award":["2022R1A2C1007622"],"award-info":[{"award-number":["2022R1A2C1007622"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The purpose of this study was to assess the cytotoxicity and antibacterial effects of AgNP-impregnated Tetracalcium phosphate-dicalcium phosphate dihydrate (TTCP-DCPD). Materials and Methods: Using in vitro experiments, the cytotoxicity of AgNP-impregnated TTCP-DCPD against fibroblasts and osteocytes was assessed in terms of cell viability by water-soluble tetrazolium salt assay. To assess antibacterial effects, a disc diffusion test was used; osteomyelitis was induced first in vivo, by injection of methicillin-resistant Staphylococcus aureus into the tibia of rats. AgNP-impregnated TTCP-DCPD bone cement was then applied at various silver concentrations for 3 or 12 weeks. Antibacterial effects were assessed by culturing and reverse transcription-polymerase chain reaction (RT-PCR). For histological observation, the bone tissues were stained using hematoxylin and eosin. Results: Cell viability was decreased by the impregnated bone cement but did not differ according to AgNP concentration. The diameter of the growth-inhibited zone of MRSA was between 4.1 and 13.3 mm on the disks treated with AgNP, indicating antimicrobial effects. In vivo, the numbers of bacterial colonies were reduced in the 12-week treatment groups compared to the 3-week treatment groups. The groups treated with a higher (10\u00d7) dose of AgNP (G2\u2013G5) showed a tendency of lower bacterial colony counts compared to the group without AgNP (G1). The PCR analysis results showed a tendency of decreased bacterial gene expression in the AgNP-impregnated TTCP-DCPD groups (G2\u2013G5) compared to the group without AgNP (G1) at 3 and 12 weeks. In the H&amp;E staining, the degree of inflammation and necrosis of the AgNP-impregnated TTCP-DCPD groups (G2\u2013G5) showed a tendency to be lower at 3 and 12 weeks compared to the control group. Our results suggest that AgNP-impregnated TTCP-DCPD cement has antimicrobial effects. Conclusions: This study indicates that AgNP-impregnated TTCP-DCPD bone cement could be considered to treat osteomyelitis.<\/jats:p>","DOI":"10.3390\/medicina59040811","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T10:11:25Z","timestamp":1682071885000},"page":"811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Efficacy of Silver Nanoparticles-Loaded Bone Cement against an MRSA Induced-Osteomyelitis in a Rat Model"],"prefix":"10.3390","volume":"59","author":[{"given":"Young Suk","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Biology, Soonchunhyang University, 22, Soonchunhyang-ro, Asan-si 31538, Chungcheoungnam-do, Republic of Korea"},{"name":"Department of Orthopedic Surgery, Soonchunhyang University Bucheon Hospital, 170, Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4003-2344","authenticated-orcid":false,"given":"Young Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Soonchunhyang University Bucheon Hospital, 170, Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Min","family":"An","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Soonchunhyang University Bucheon Hospital, 170, Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Republic of Korea"},{"name":"Department of Medical Sciences, Soonchunhyang University, 22, Soonchunhyang-ro, Asan-si 31538, Chungcheoungnam-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Kyoung","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Soonchunhyang University Bucheon Hospital, 170, Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Republic of Korea"},{"name":"Department of Medical Sciences, Soonchunhyang University, 22, Soonchunhyang-ro, Asan-si 31538, Chungcheoungnam-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Koo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Soonchunhyang University Bucheon Hospital, 170, Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e157","DOI":"10.3928\/01477447-20140124-19","article-title":"CT characterizing the anatomy of uninjured ankle syndesmosis","volume":"37","author":"Mendelsohn","year":"2014","journal-title":"Orthopedics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5155","DOI":"10.1016\/j.biomaterials.2007.08.003","article-title":"Advancements in molecular epidemiology of implant infections and future perspectives","volume":"28","author":"Montanaro","year":"2007","journal-title":"Biomaterials"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"832","DOI":"10.5301\/ijao.5000163","article-title":"The use of antimicrobial-impregnated PMMA to manage periprosthetic infections: Controversial issues and the latest developments","volume":"35","author":"Tan","year":"2012","journal-title":"Int. J. Artif. Organs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fcimb.2013.00101","article-title":"Apoptosis-associated uncoupling of bone formation and resorption in osteomyelitis","volume":"3","author":"Marriott","year":"2013","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/(SICI)1097-4636(19970605)35:3<273::AID-JBM1>3.0.CO;2-E","article-title":"Effects of hydroxypropyl methylcellulose and other gelling agents on the handling properties of calcium phosphate cement","volume":"35","author":"Cherng","year":"1997","journal-title":"J. Biomed. Mater. Res. Off. J. Soc. Biomater. Jpn. Soc. Biomater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0140-6736(04)16727-5","article-title":"Osteomyelitis","volume":"364","author":"Lew","year":"2004","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.actbio.2011.11.017","article-title":"Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review","volume":"8","author":"Bose","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Likus, W., Bajor, G., and Siemianowicz, K. (2013). Nanosilver-does it have only one face?. Acta Biochim. Pol., 60.","DOI":"10.18388\/abp.2013_2013"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1590\/S1984-82502013000100003","article-title":"Osteomyelitis: An overview of antimicrobial therapy","volume":"49","author":"Gomes","year":"2013","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1007\/s10853-008-2527-z","article-title":"Calcium orthophosphate cements for biomedical application","volume":"43","author":"Dorozhkin","year":"2008","journal-title":"J. Mater. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1302\/0301-620X.97B5.33336","article-title":"Silver nanoparticles and their orthopaedic applications","volume":"97","author":"Brennan","year":"2015","journal-title":"Bone Jt. J."},{"key":"ref_12","first-page":"930","article-title":"Silver nanoparticles and its potential applications: A review","volume":"7","author":"Agrawal","year":"2018","journal-title":"J. Pharmacogn. Phytochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s10856-021-06590-y","article-title":"Synthesis of silver nanoparticle-decorated hydroxyapatite nanocomposite with combined bioactivity and antibacterial properties","volume":"32","author":"Bee","year":"2021","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s00204-012-1007-z","article-title":"Nanosilver: Application and novel aspects of toxicology","volume":"87","author":"Schluesener","year":"2013","journal-title":"Arch. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/jor.22357","article-title":"Silver oxide-containing hydroxyapatite coating has in vivo antibacterial activity in the rat tibia","volume":"31","author":"Akiyama","year":"2013","journal-title":"J. Orthop. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3109\/03639045.2013.845840","article-title":"Comparison of antibacterial activity of Ag nanoparticles synthesized from leaf extract of Parthenium hystrophorus L in aqueous media and gentamicin sulphate: In-vitro","volume":"41","author":"Anwar","year":"2015","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1099\/jmm.0.46124-0","article-title":"Antimicrobial activities of silver dressings: An in vitro comparison","volume":"55","author":"Ip","year":"2006","journal-title":"J. Med. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"He, Q., Chen, H., Huang, L., Dong, J., Guo, D., Mao, M., Kong, L., Li, Y., Wu, Z., and Lei, W. (2012). Porous surface modified bioactive bone cement for enhanced bone bonding. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042525"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/ajcp\/45.4_ts.493","article-title":"Antibiotic susceptibility testing by a standardized single diffusion method","volume":"45","author":"Bauer","year":"1966","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1007\/s10856-013-5014-2","article-title":"Composition and properties of silver-containing calcium carbonate\u2013calcium phosphate bone cement","volume":"24","author":"Jacquart","year":"2013","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.2147\/IJN.S14572","article-title":"Antibacterial properties of silver nanoparticles in three different sizes and their nanocomposites with a new waterborne polyurethane","volume":"5","author":"Liu","year":"2010","journal-title":"Int. J. Nanomed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.nano.2011.06.014","article-title":"Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles","volume":"8","author":"Thi","year":"2012","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_23","first-page":"48","article-title":"Silver nanoparticles\u2013allies or adversaries?","volume":"20","author":"Bartlomiejczyk","year":"2013","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/j.tiv.2014.06.005","article-title":"Exposure to silver nanoparticles induces size-and dose-dependent oxidative stress and cytotoxicity in human colon carcinoma cells","volume":"28","author":"Rumpker","year":"2014","journal-title":"Toxicol. In Vitro"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5967","DOI":"10.1016\/j.biomaterials.2012.05.031","article-title":"Biofilm formation in Staphylococcus implant infections. A review of molecular mechanisms and implications for biofilm-resistant materials","volume":"33","author":"Arciola","year":"2012","journal-title":"Biomaterials"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/ICL.0000000000000066","article-title":"Study on Prevalence, Antibiotic Susceptibility, and tuf Gene Sequence\u2013Based Genotyping of Species-Level of Coagulase-Negative Staphylococcus Isolated from Keratitis Caused by Using Soft Contact Lenses","volume":"42","author":"Faghri","year":"2016","journal-title":"Eye Contact Lens"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S0140-6736(02)07877-7","article-title":"Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients","volume":"359","author":"Gillet","year":"2002","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/SAP.0b013e318061d310","article-title":"Effect of Heparin on Production of Transforming Growth Factor (TGF)-\u03b21 and TGF-\u03b21 mRNA Expression by Human Normal Skin and Hyperplastic Scar Fibroblasts","volume":"60","author":"Fan","year":"2008","journal-title":"Ann. Plast. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00441-005-0066-3","article-title":"Isolated primary osteocytes express functional gap junctions in vitro","volume":"323","author":"Gu","year":"2006","journal-title":"Cell Tissue Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4999","DOI":"10.1128\/AAC.00584-11","article-title":"Daptomycin, fosfomycin, or both for treatment of methicillin-resistant Staphylococcus aureus osteomyelitis in an experimental rat model","volume":"55","author":"Poeppl","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2144\/0000113876","article-title":"Isolation and culture of primary osteocytes from the long bones of skeletally mature and aged mice","volume":"52","author":"Stern","year":"2012","journal-title":"Biotechniques"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1007\/s11908-012-0286-0","article-title":"Chronic osteomyelitis","volume":"14","author":"Jugun","year":"2012","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.4161\/biom.22905","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":"Biomatter"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1021\/acsami.6b14912","article-title":"Sustainable release of vancomycin from silk fibroin nanoparticles for treating severe bone infection in rat tibia osteomyelitis model","volume":"9","author":"Mottaghitalab","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12891-015-0704-1","article-title":"Antibiotic-impregnated cement spacer as definitive management for osteomyelitis","volume":"16","author":"Qiu","year":"2015","journal-title":"BMC Musculoskelet. Disord."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/apm.12687","article-title":"Orthopaedic biofilm infections","volume":"125","author":"Zimmerli","year":"2017","journal-title":"APMIS"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.actbio.2019.01.015","article-title":"Implantable antimicrobial biomaterials for local drug delivery in bone infection models","volume":"93","author":"Caplin","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.nano.2015.11.016","article-title":"Silver nanoparticles: A new view on mechanistic aspects on antimicrobial activity","volume":"12","author":"Seabra","year":"2016","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1701503","DOI":"10.1002\/adhm.201701503","article-title":"Antibacterial activity of silver nanoparticles: Structural effects","volume":"7","author":"Tang","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jallcom.2018.02.334","article-title":"Antibacterial activity of silver nanoparticles (AgNP) confined to mesostructured silica against methicillin-resistant Staphylococcus aureus (MRSA)","volume":"747","author":"Chien","year":"2018","journal-title":"J. Alloys Compd."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1128\/AAC.00740-10","article-title":"Treatment with linezolid or vancomycin in combination with rifampin is effective in an animal model of methicillin-resistant Staphylococcus aureus foreign body osteomyelitis","volume":"55","author":"Vergidis","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/j.1742-481X.2012.00977.x","article-title":"Cytotoxicity of silver dressings on diabetic fibroblasts","volume":"10","author":"Zou","year":"2013","journal-title":"Int. Wound J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3164\/jcbn.11-70","article-title":"Metal nanoparticle-induced micronuclei and oxidative DNA damage in mice","volume":"50","author":"Song","year":"2012","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_44","first-page":"77","article-title":"Antibacterial activity of silver-nanoparticles against Staphylococcus aureus and Escherichia coli","volume":"39","author":"Kim","year":"2011","journal-title":"Microbiol. Biotechnol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"850","DOI":"10.5897\/AJMR2016.7908","article-title":"Antibacterial activity of silver-nanoparticles against Staphylococcus aureus","volume":"10","author":"Ydollahi","year":"2016","journal-title":"Afr. J. Microbiol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.biotechadv.2008.09.002","article-title":"Silver nanoparticles as a new generation of antimicrobials","volume":"27","author":"Rai","year":"2009","journal-title":"Biotechnol. Adv."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s00256-007-0342-2","article-title":"A different perspective for radiological evaluation of experimental osteomyelitis","volume":"36","author":"Aktekin","year":"2007","journal-title":"Skelet. Radiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4575","DOI":"10.1039\/D0TB00074D","article-title":"Preparation and evaluation of osteogenic nano-MgO\/PMMA bone cement for bone healing in a rat critical size calvarial defect","volume":"8","author":"Li","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s10534-010-9381-6","article-title":"Antibacterial effect of silver nanoparticles on Staphylococcus aureus","volume":"24","author":"Li","year":"2011","journal-title":"Biometals"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.carbon.2020.03.009","article-title":"Quaternary ammonium carbon quantum dots as an antimicrobial agent against gram-positive bacteria for the treatment of MRSA-infected pneumonia in mice","volume":"163","author":"Zhao","year":"2020","journal-title":"Carbon"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/4\/811\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:20:47Z","timestamp":1760124047000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/4\/811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":50,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["medicina59040811"],"URL":"https:\/\/doi.org\/10.3390\/medicina59040811","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]}}}