Translation-driven design: development of an antibiotic-loaded hydrogel for the management of orthopaedic...

Orthopedic device-related infection (ODRI) is a devastating complication, often requiring repeated revision surgeries and prolonged antibiotic treatment. Injectable biodegradable biomaterials that deliver and maintain high local concentrations of antibiotics to the surgical field may eliminate the need for additional surgeries while improving treatment outcomes. In this study, we introduce a Gel for Delivery of Antibiotics (GEDAI) for local administration of tobramycin (T), gentamicin (G) or gentamicin-vancomycin (GV). GEDAI was developed with translatability and ease of intraoperative handling as design goals. GEDAI displayed storage and loss moduli, shear thinning, and elastic recovery properties appropriate for intraoperative applications, with good adhesion to stainless steel and tissues but reduced adhesion to surgical gloves. In vitro assays showed no adverse effects of the GEDAI on viability of fibroblasts, macrophages and endothelial cells, or osteogenic differentiation of human bone marrow stromal cells (hBMSCs). Methicillin susceptible and resistant Staphylococcus aureus (MSSA and MRSA), growing in planktonic culture or biofilm, were significantly reduced after exposure to the antibiotic loaded-GEDAI compared to GEDAI without antibiotics (p < 0.05). In three distinct in vivo studies in sheep, GEDAI-T reached a peak local concentration above 2000 μg/mL within 2 h and substantially reduced bacterial counts in two models with implant retention (GEDAI-T or GEDAI-G), and completely eradicated infection in an implant exchange model (GEDA-GV). GEDAI directly targets two unmet needs in ODRI: achieving bactericidal local concentrations without systemic toxicity and providing a ready-to-use formulation. The antibiotic-loaded GEDAI formulations promise to improve treatment outcomes in challenging infection cases, potentially reducing healthcare costs and patient burden in postoperative infection management.