title: A resorbable antibiotic-eluting polymer composite bone void filler for perioperative infection prevention in a rabbit radial defect model.
abstract: Nearly 1.3 million total joint replacement procedures are performed in the United States annually, with numbers projected to rise exponentially in the coming decades. Although finite infection rates for these procedures remain consistently low, device-related infections represent a significant cause of implant failure, requiring secondary or revision procedures. Revision procedures manifest several-fold higher infection recurrence rates. Importantly, many revision surgeries, infected or not, require bone void fillers to support the host bone and provide a sufficient tissue bed for new hardware placement. Antibiotic-eluting bone void fillers (ABVF), providing both osteoconductive and antimicrobial properties, represent one approach for reducing rates of orthopedic device-related infections. Using a solvent-free, molten-cast process, a polymer-controlled antibiotic-eluting calcium carbonate hydroxyapatite (HAP) ceramic composite BVF (ABVF) was fabricated, characterized, and evaluated in vivo using a bacterial challenge in a rabbit radial defect window model. ABVF loaded with tobramycin eliminated the infectious burden in rabbits challenged with a clinically relevant strain of Staphylococcus aureus (inoculum as high as 10⁷ CFU). Histological, microbiological, and radiographic methods were used to detail the effects of ABVF on microbial challenge to host bone after 8 weeks in vivo. In contrast to the HAP/BVF controls, which provided no antibiotic protection and required euthanasia 3 weeks post-operatively, tobramycin-releasing ABVF animals showed no signs of infection (clinical, microbiological, or radiographic) when euthanized at the 8-week study endpoint. ABVF sites did exhibit fibrous encapsulation around the implant at 8 weeks. Local antibiotic release from ABVF to orthopedic sites requiring bone void fillers eliminated the periprosthetic bacterial challenge in this 8-week in vivo study, confirming previous in vitro results.
authors: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, 84112-5820, United States of America.
authors: Benjamin D
authors: BD
authors: Brooks
authors: Elute Inc., 417 Wakara Way, Suite 3510, Salt Lake City, Utah, 84108, United States of America.
authors: Kristofer D
authors: KD
authors: Sinclair
authors: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, 84112-5820, United States of America; Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112-5820, United States of America.
authors: David W
authors: DW
authors: Grainger
authors: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, 84112-5820, United States of America.
authors: Amanda E
authors: AE
authors: Brooks
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D018786:Bone Substitutes / Q000737:chemistry*; D002119:Calcium Carbonate / Q000737:chemistry; D002516:Ceramics / Q000737:chemistry; D017886:Durapatite / Q000737:chemistry; D059035:Perioperative Period; D011108:Polymers / Q000737:chemistry*; D016459:Prosthesis-Related Infections / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits; D011859:Radiography; D011884:Radius / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000601:surgery*; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D018786:Bone Substitutes; D011108:Polymers; D017886:Durapatite; D002119:Calcium Carbonate; D014031:Tobramycin