Vancomycin release kinetics for treatment of bone tissue infection: design of a loaded scaffold and evaluation of a dynamic model

Abstract

The development of local drug delivery systems (DDS) has emerged as a promising strategy for targeted therapeutic applications, enabling high drug concentrations at specific sites while minimizing systemic toxicity. However, the evaluation of drug release kinetics remains challenging due to the limitations of current in vitro models, which often fail to replicate physiological conditions. To address this issue, dynamic models, such as flow perfusion bioreactors, offer a more realistic approach to studying DDS, particularly in cases where prolonged drug release is required, such as the prevention of surgical site infections (SSI) in bone grafts. In this study, a macroporous hydroxyapatite (HA) scaffold was designed through robocasting, an additive manufacturing technique, to obtain a bone substitute with a controlled macroporous architecture. HA was chosen for its chemical similarity to the mineral phase of bone, its non-biodegradability, and its ability to support antibiotic loading and release. Vancomycin, a broad-spectrum antibiotic commonly used against Staphylococcus aureus, was incorporated into a thermosensitive chitosan hydrogel to regulate its release kinetics. The loaded scaffolds were evaluated using a perfusion bioreactor to model the bone microenvironment. The antibiotic release profile was determined using high-performance liquid chromatography (HPLC) and an iterative algorithm. The objective is to establish a proof of concept and demonstrate the relevance of a dynamic, animal-free model for studying the kinetics of local antibiotic release. The results showed that the combination of a macroporous HA scaffold and a chitosan hydrogel enabled sustained antibiotic release over time. Furthermore, in vitro antibacterial assays confirmed the efficacy of the released vancomycin against Staphylococcus aureus. This study highlights the potential of using perfusion bioreactors and additive manufacturing techniques to develop physiologically relevant DDS models, ultimately contributing to the refinement of antibiotic delivery strategies.