Authors: Antoci Jr, Valentin*; Parvizi Javad; Freeman, Theresa A.; Hoffsommer, Hellen M.; Wickstrom, Eric; Zeiger, Allen R.; Shapiro, Irving M; Hickok, Noreen J.; Adams, Christopher S.
Title: Vancomycin-modified Surface Effective Against Peri-Prosthetic Infection
Addresses: 1015 Walnut St. 501, Philadelphia, PA 19107
Purpose: Periprosthetic infection (PPI) is a challenging complication of joint arthroplasty. We hypothesized that implant surfaces that are covalently modified with antibiotics can inhibit bacterial colonization and development of subsequent PPI.
Methods: Modification of Ti alloy. 1mm diameter Ti90Al6V4 (Ti, Goodfellow) rods were passivated, silanized with APTS, reacted twice with AEEA, and covalently linked with Vancomycin. Animal Testing. All protocols were approved by the IACUC of Thomas Jefferson University. Wistar rats (Charles Rivers), 300-350 g, were anesthetized with IP ketamine/xylazine, with maintenance isoflurane, and buprenorphine for pain control bid. Infection was induced by injection of 1500 CFU S. aureus into the femoral canal. Control Ti and TiVAN were sterilized by incubation in 70% ethanol for 15 min, rinsed 3X with PBS, and implanted retrograde in the femoral canal. At harvest, animals were euthanized with CO2, femora were radiographed and harvested followed by microCT imaging. The bacterial quantification on the Ti pin was performed by sonication and serial dilution plating for CFU counts. Furthermore, the femora were decalcified with EDTA, sectioned with paraffin, and evaluated for bone infection.
Results: All animals showed signs of infection within the first few post-operative days with increased soft tissue swelling and limited mobility. All animals were partially weight bearing, mainly with preference for the control side. At 1 week 75% of the animals showed signs of periprosthetic infection easily diagnosable by radiography. In 92% of the animals the left and right sides showed observable differences, all indicating infection on the control side. In one animal the infection manifested on the treatment side partially due to the pin insertion penetrating the bone cortex. In those cases, periosteal elevation and enlargement of the femoral canal were most common. In 30% of animals advanced bone destruction was seen in the form of lytic areas, bone cysts, and aggressive remodeling. The ratios progressed similarly to week 2 through 4. More aggressive remodeling is observed with time, with no change in infection rates or ratios. At harvest, infection was clearly prevalent on the control side, the treatment side receiving the vancomycin-modified rod showed decreased signs of infection compared to the control limb. After culturing the implant, significantly fewer bacteria were present on the vancomycin-modified rod
Discussion: We have previously reported on the engineering of a new implant modification that incorporates a nanoscale surface of covalently linked antibiotics. In this report we test our surface in a mammalian periprosthetic model, showing successful inhibition of peri-prosthetic infection. This novel technology may have a role in management of periprosthetic infection in the clinical arena.
