Comparisons of Release of Several Antibiotics from Antimicrobial Polymer-Coated Allograft Bone Void Filler
International Journal of Biomedical Materials Research
Volume 1, Issue 2, August 2013, Pages: 21-25
Received: Aug. 12, 2013;
Published: Jan. 10, 2014
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Benjamin D. Brooks, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA
Sherry N. Davidoff, Department of Bioengineering, University of Utah, Salt Lake City, UT, USA
David W. Grainger, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT, USA
Amanda E. Brooks, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA
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Osteomyelitis remains a significant complication in orthopedic surgeries. Although infection rates remain steady at 1-3% for primary orthopedic surgeries, overall numbers of orthopedic procedures are increasing, corresponding to earlier and more frequent surgical intervention for an active, aging population. To address this dangerous surgical complication, degradable polycaprolactone (PCL) polymer/antibiotic solutions were coated over allograft bone void filler. Local in vitro release of ciprofloxacin, vancomycin, oxacillin, tobramycin, or rifampicin from a polymer-controlled, antibiotic-releasing bone graft void filler and monitored in vitro allowed the criterion for successful local antibiotic-releasing devices to be expanded. Although each antibiotic exhibited a different release profile based on their formulation and chemical structure, allowing the potential for engineering combinatorial therapy with microbicidal activity, bacterial killing activity in vitro was demonstrated efficacious out to a clinically relevant 8-week time point. In addition to proposing an expanded criterion for successful local antibiotic-releasing devices, this study demonstrates that allograft bone can act as a local, controlled drug release matrix in bone sites. This combination device provides osteoconductive potential in bone voids while mitigating the potential for operatively sourced opportunistic infectious complications during orthopedic repairs as well as primary and revision arthroplasties
Controlled Release, Antibiotic Delivery, Orthopedic Infection, Antibiotic Combination Therapy, Osteomyelitis, Bone Void Fillers, Antimicrobial Allograft, Polycaprolactone
To cite this article
Benjamin D. Brooks,
Sherry N. Davidoff,
David W. Grainger,
Amanda E. Brooks,
Comparisons of Release of Several Antibiotics from Antimicrobial Polymer-Coated Allograft Bone Void Filler, International Journal of Biomedical Materials Research.
Vol. 1, No. 2,
2013, pp. 21-25.
A. Alex Jahangir, MD; Ryan M. Nunley, MD; Samir Mehta, MD; Alok Sharan, MD; and the, Washington Health Policy Fellows. Bone-graft subsitutes in orthpaedic surgery [Internet]. AAOS; 2008 Jan. Available from: http://www.aaos.org/news/aaosnow/jan08/reimbursement2.asp
Landersdorfer CB, Bulitta JB, Kinzig M, Holzgrabe U, Sörgel F. Penetration of Antibacterials into Bone. Clin Pharmacokinet. 2009;48(2):89–124.
Campoccia D, Montanaro L, Speziale P, Arciola CR. Antibiotic-loaded biomaterials and the risks for the spread of antibiotic resistance following their prophylactic and therapeutic clinical use. Biomaterials. 2010;31(25):6363–77.
Brooks BD, Brooks AE, Grainger DW. Antimicrobial Medical Devices in Preclinical Development and Clinical Use. In: Moriarty TF, Zaat SAJ, Busscher HJ, editors. Biomater Assoc Infect [Internet]. Springer New York; 2013 [cited 2012 Oct 30]. p. 307–54. Available from: http://www.springerlink.com/content/rp22657g55495648/abstract/
Lucke M, Schmidmaier G, Sadoni S, Wildemann B, Schiller R, Haas N., et al. Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats. Bone. 2003 May;32(5):521–31.
B Burlington. FDA Public Health Notice Potential Hypersensitivity Reactions To Chlorhexidine-Impregnated Medical Devices [Internet]. FDA; 2013 Feb. Available from: http://www.medline.com/wound-skin-care/silvasorb/lit/FDA%20Health%20Notice%20on%20CHG.pdf
Anagnostakos K, Fürst O, Kelm J. Antibiotic-impregnated PMMA hip spacers: current status. Acta Orthop. 2006;77(4):628–37.
Kanellakopoulou K, Giamarellos-Bourboulis EJ. Carrier systems for the local delivery of antibiotics in bone infections. Drugs. 2000 Jun;59(6):1223–32.
Kluin OS, van der Mei HC, Busscher HJ, Neut D. Biodegradable vs non-biodegradable antibiotic delivery devices in the treatment of osteomyelitis. Expert Opin Drug Deliv. 2013 Mar;10(3):341–51.
Davidoff SN, Call BP, Hogrebe PC, Grainger DW, Brooks AE. A robust method to coat allograft bone with a drug-releasing polymer shell-biomed 2010. Biomed Sci Instrum. 2010;46:184.
Amanda E. Brooks, Benjamin D. Brooks Sherry N. Davidoff, Paul C. Hogrebe,, Mark A. Fisher, David W. Grainger. Polymer-Controlled Release of Tobramycin from Bone Graft Void Filler. Drug Deliv Transl Res. In Press;
Grainger DW. Targeted delivery of therapeutics to bone and connective tissues. Adv Drug Deliv Rev. 2012 Sep;64(12):1061–2.
CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Seventeenth Informational Supplement [Internet]. Clinical Laboratory Standards Institute; 2007 Jan. Available from: http://www.microbiolab-bg.com/CLSI.pdf
Neut D, van de Belt H, van Horn JR, van der Mei HC, Busscher HJ. The effect of mixing on gentamicin release from polymethylmethacrylate bone cements. Acta Orthop Scand. 2003 Dec;74(6):670–6.
Van de Belt H, Neut D, Schenk W, van Horn JR, van der Mei HC, Busscher HJ. Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation. Acta Orthop Scand. 2000 Dec;71(6):625–9.