Micron-thin bactericidal sol-gel coated intramedullary nails for the prevention and treatment of infection
Year: 2016
Type: article
Abstract: Event Abstract Back to Event Micron-thin bactericidal sol-gel coated intramedullary nails for the prevention and treatment of infection Haibo Qu1, Christine Knabe2, Zosia Zawacki3, Thomas Schaer3 and Paul Ducheyne1 1 University of Pennsylvania, Bioengineering, United States 2 Philipps University, Department of Experimental Orofacial Medicine, Germany 3 University of Pennsylvania School of Veterinary Medicine, Comparative Orthopaedic Research Laboratory, United States Introduction: Implant associated infections continue to result in increased morbidity, pain and suffering to the patient and are linked to substantial cost to the health care system. A major factor contributing to the development of implant associated infections is rapid bacterial adherence resulting in biofilm formation on the implant surface[1]. The biofilm-embedded bacteria are up to 1000 times more resistant to antibiotics. In our program we pursue the use of a novel, controlled release sol-gel nanotechnology for the continuous delivery of bactericidal molecules. These films are firmly adherent and the release of bactericidal molecules can be easily adjusted for different applications[2]. Herein, we report on the prevention of infection using micron-thin bactericidal sol-gel films on intramedullary (IM) nails in a sheep osteomyelitis model. Methods: Custom-made IM nails (Ti6Al4V, length of 140mm and diameter of 6mm) were sandblasted, cleaned and dried prior to dip-coating. IM nails were coated by dipping in a sol solution with or without vancomycin using a previously reported procedure[2],[3]. Sols with nominal vancomycin concentrations of 5wt%, 10wt%, or 20wt% were used for the vancomycin containing sol-gel film (SGV). Sol containing no vancomycin was used for control sol-gel film (SG). The micron-thin SG and SGV films consisted of 15 layers consecutively deposited. The SG coated and SGV coated implants were sterilized using STERRAD (gas plasma sterilization method, Advanced Sterilization Products). The in vitro vancomycin release was determined using a phosphate buffered saline solution at 37°C, with daily solution exchange and gentle shaking. Concentrations of released vancomycin were measured spectrophotometrically at 280 nm. To assess the vancomycin concentration in the intramedullary canal, two sheep received SGV implants were implanted with ultrafiltrate probe in the medullary cavity to collect interstitial fluid. For the infection study, total of 30 skeletally mature Dorset-cross were operated upon. To establish a model that recapitulates clinical signs of osteomyelitis, animals received one of two different doses of either 106 or 108 colony-forming units (CFU) of S. aureus, (ATCC 25923), instilled into the medullary tibial canal. Animals were sacrificed at 4 and 12 weeks postoperative. Eighteen sheep that received either SGV or SG coated nail were sacrificed at 4 weeks. Twelve sheep receiving either SGV or SG coated implants were sacrificed at 12 weeks. To determine bacterial presence, culture swabs were taken from the medullary canal. The tibiae and implants were then harvested using aseptic techniques and radiographed in µCT scanner. The histomorphologic and immunohistochemical analyses on stained thin sections were performed. Results: The time-dependent in vitro release of vancomycin from micron-thin sol-gel films is shown in Figure 1 for release duration up to 11 weeks. The release profile showed a linear release regardless of the vancomycin concentration. In addition, the vancomycin release rate increased with higher drug content. The vancomycin released from sol-gel film quickly built up a local vancomycin concentration exceeding MIC (2mg/ml, red dotted line) 24 hours after implantation. Such high concentration maintained for 384 hours (16 days) (Figure 2), the longest time point measured in both sheep. One month after surgery, the treatment SGV films, but not the control SG film, prevented intramedullary infections after challenged with S. Aureus. Discussion: The amount of vancomycin and rate of release can be adjusted by varying the vancomycin concentration of the SGV film. By optimizing the sol-gel condition and vancomycin concentration, sol-gel films can provide vancomycin exceeding MIC 24 hours after implantation, and such high concentration can be maintained for more than 16 days (Figure 2). Such high and prolonged localized vancomycin concentration in tibial medullary cavity is beneficial in preventing and treating intramedullary infections. Conclusion: This study shows vancomycin released from sol-gel film maintained a high local vancomycin concentration exceeding MIC for more than 16 days inside the sheep medullary cavity. Such high local vancomycin concentration can successfully prevent osteomyelitis development. This work is supported by the U.S. Army contract #W81XWH-10-2-0156.References:[1] Stoodley P, et al. Orthopaedic biofilm infections. Current orthopaedic practice 2011;22:558-63.[2] Radin S, et al, Biomaterials 2007;28:1721-1729.[3] Adams CS, et al, Journal of Orthopaedic Research 2009;27:701-709. Keywords: Infection, in vivo, Drug delivery, Implant Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Anti-infective biomaterials Citation: Qu H, Knabe C, Zawacki Z, Schaer T and Ducheyne P (2016). Micron-thin bactericidal sol-gel coated intramedullary nails for the prevention and treatment of infection. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02341 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Haibo Qu Christine Knabe Zosia Zawacki Thomas Schaer Paul Ducheyne Google Haibo Qu Christine Knabe Zosia Zawacki Thomas Schaer Paul Ducheyne Google Scholar Haibo Qu Christine Knabe Zosia Zawacki Thomas Schaer Paul Ducheyne PubMed Haibo Qu Christine Knabe Zosia Zawacki Thomas Schaer Paul Ducheyne Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W2329013960