Abstract
We previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.
Highlights
We previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles
ΜCT imaging of each formulation before antibiotic loading provided visual evidence that the S1 scaffold was more dense than the K20 scaffold (Fig. 1), and based on the amount of phosphate-buffered saline (PBS) remaining after saturation of each scaffold formulation the K20 scaffold was found to take up an average of approximately 2.30-fold more fluid than the S1 scaffold, confirming that the modifications made to the K20 scaffold increase its surface area and porosity relative to the S1 scaffold
For both the S1 and K20 scaffolds loaded at concentrations of 10 or 100 mg/ mL of vancomycin, the concentrations antibiotic in the eluted samples obtained on day 10 remained above the breakpoint minimum inhibitory concentration (MIC) that defines a vancomycin-sensitive strain of S. aureus (≤ 2.0 μg/mL)
Summary
We previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The resulting bone defects are problematic because they involve a breach of the skin and occur in non-sterile environments, making them highly susceptible to infection The treatment of these injuries requires an intensive interdisciplinary clinical approach that includes long-term systemic antibiotic therapy and surgical debridement to remove damaged and contaminated bone and soft tissues[1,2,3,4,5]. The compromised wound environment often makes it necessary to augment systemic therapy using some form of local antibiotic delivery, the goal being to obtain antibiotic levels at the site of injury that exceed those that can be achieved using systemic methods alone and that are sufficient to overcome the intrinsic resistance associated with formation of a bacterial biofilm on damaged bone and soft tissues[7,8,9,10,11,12,13] Despite such intensive medical and surgical intervention, recurrent infection and even amputation are far-too-common outcomes. We determined the minimum amount of antibiotic required to achieve this effect
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