Modelling two-stage antibiotic release from orthopedic fixation pins to prevent post-op osteomyelitis

Abstract

The first six hours following orthopedic implantation is a decisive period for preventing bacterial adhesion to ensure an implant’s long-term success. If bacterial adhesion is not adequately impeded, a biofilm will form, acting as a diffusion barrier to slow down the implant integration process. Current therapies to treat osteomyelitis and other forms of implant-related infections include physical removal of the infected device, revision surgery, and prolonged antibiotic therapy. However, osteomyelitis still occurs at significant rates, and affected patients often require surgical adjustment or systemic antibiotic dosages. This project considers a cylindrical drug-eluting pin, comprised of a reservoir of packed mesoporous silica MCM-48 microparticles, where the antibiotic (linezolid) is adsorbed. As simulated body fluid flows into the pin, the drug is desorbed from the microparticles and diffuses down its concentration gradient to be released in a sustained manner. A one dimensional diffusive mass transport simulation in COMSOL 5.3 Multiphysics was used to quantitatively simulate this process with the objective of optimizing design options such as porosity and pin geometry with respect to drug delivery, specifically the concentration of the drug on the surface of the pin where bacterial adhesion occurs. We modeled a pin with 17% wall porosity packed with 440 nm silica beads. These dimensions can be altered to improve current fixation pin designs which can facilitate treatment procedures. Our model exhibited higher rates of release when compared to the experimental data, with 50% of total drug release achieved at approximately 8.5 and 40 hours respectively. This can be explained by the limited volume of SBF used in the experiment in contrast to the “infinite” amount of SBF that was assumed in our model, leading to higher rates of diffusion and release in our computational model. Optimization of porosity revealed that 20% porosity leads to a drug release profile that maximizes the amount of time above the minimal bactericidal concentration (MBC) and minimal inhibitory concentration (MIC). In the design of future pins, since increases in porosity are associated with decreases in mechanical strength and increases in manufacturing costs, the resulting changes in the mechanical properties and manufacturing process are significant factors that must be taken into account when improving the existing design of orthopedic devices.