{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T22:39:18Z","timestamp":1778279958164,"version":"3.51.4"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T00:00:00Z","timestamp":1573171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"North Dakota Department of Commerce","award":["Phase I Venture Grant"],"award-info":[{"award-number":["Phase I Venture Grant"]}]},{"name":"ND EPSCoR","award":["Doctoral Dissertation Fellowship"],"award-info":[{"award-number":["Doctoral Dissertation Fellowship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>In spite of advances in Total Joint Replacements (TJR), infection remains a major concern and a primary causative factor for revision surgery. Current clinical standards treat these osteomyelitis infections with antibiotic-laden poly(methyl methacrylate) (PMMA)-based cement, which has several disadvantages, including inadequate local drug release kinetics, antibiotic leaching for a prolonged period and additional surgical interventions to remove it, etc. Moreover, not all antibiotics (e.g., rifampicin, a potent antibiofilm antibiotic) are compatible with PMMA. For this reason, treatment of TJR-associated infections and related complications remains a significant concern. The objective of this study was to develop a polymer-controlled dual antibiotic-releasing bone void filler (ABVF) with an underlying osseointegrating substrate to treat TJR implant-associated biofilm infections. An ABVF putty was designed to provide sustained vancomycin and rifampicin antibiotic release for 6 weeks while concurrently providing an osseointegrating support for regrowth of lost bone. The reported ABVF showed efficient antibacterial and antibiofilm activity both in vitro and in a rat infection model where the ABVF both showed complete bacterial elimination and supported bone growth. Furthermore, in an in vivo k-wire-based biofilm infection model, the ABVF putty was also able to eliminate the biofilm infection while supporting osseointegration. The retrieved k-wire implants were also free from biofilm and bacterial burden. The ABVF putty delivering combination antibiotics demonstrated that it can be a viable treatment option for implant-related osteomyelitis and may lead to retention of the hardware while enabling single-stage surgery.<\/jats:p>","DOI":"10.3390\/pharmaceutics11110592","type":"journal-article","created":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T11:30:19Z","timestamp":1573212619000},"page":"592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Extended Release Combination Antibiotic Therapy from a Bone Void Filling Putty for Treatment of Osteomyelitis"],"prefix":"10.3390","volume":"11","author":[{"given":"Raquib","family":"Hasan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kambri","family":"Schaner","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, North Dakota State University, Fargo, ND 58102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Department of Microbiological Sciences, North Dakota State University, Fargo, ND 58102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbey","family":"Wohlers","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, North Dakota State University, Fargo, ND 58102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Shreffler","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Codi","family":"Schaper","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, North Dakota State University, Fargo, ND 58102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hariharaputhiran","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND 58102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9785-5969","authenticated-orcid":false,"given":"Amanda","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.arth.2007.10.017","article-title":"Infection Burden for Hip and Knee Arthroplasty in the United States","volume":"23","author":"Kurtz","year":"2008","journal-title":"J. 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