Introduction: Implant-associated infections (IAIs) remain a critical challenge in orthopedic surgery, driven by biofilm formation and rising antimicrobial resistance (AMR). Localized, on-demand drug delivery systems offer a promising alternative to systemic antibiotics by providing spatial and temporal control over therapeutic release. This study optimized a thermoresponsive hydrogel system based on Pluronic® F-127 to achieve four specific goals: enable on-demand activation via an alternating magnetic field (AMF), reduce the gel-sol transition temperature, enhance aqueous stability, and suppress passive release.

Methods: Hydrogels were formulated using 20 wt.% Pluronic F127 (20PF127) with sodium alginate (SA), calcium chloride (CaCl₂) for ionic crosslinking, and superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic responsiveness. The formulations were evaluated using the inverted tube method for gelation, stability assessment under physiological conditions, and release kinetics studies under both passive and on-demand conditions, using a model dye. AMF-triggered release was tested from Ti-6Al-4V implant reservoirs.

Results: Two formulations were identified: a non-SPION (20PF127/3SA/CaCl2) hydrogel and a SPION-loaded (20PF127/3SA/CaCl2/SPIONs) hydrogel. Both demonstrated significant improvements over the pure 20PF127 control. SA and CaCl₂ incorporation reduced the gel-sol transition temperature from 78 °C to 55 °C in the non-SPION and to 52 °C in the SPION-loaded formulations, while enhancing structural stability for up to 7 days under physiological conditions. Also, the SPION-loaded hydrogel retained the dye for up to 4 hours longer, thus reducing early cumulative release by approximately 2-fold compared to 20PF127. Furthermore, on-demand release testing with the non-SPION formulation revealed three distinct AMF-triggered profiles, enabling full dye release within 2 hours, matching the total release typically achieved through passive diffusion only after 24 to 48 hours.

Discussion and conclusions: The SPION-loaded hydrogel demonstrated superior passive release suppression and similar hydrogel stability to the non-SPION variant, although under the tested conditions, it did not achieve substantial on-demand release. In parallel, the non-SPION formulation exhibited on-demand release when integrated with titanium implants, leveraging implant-assisted heating for controlled delivery. Together, these findings establish a proof-of-concept hydrogel platform for localized, externally controlled drug delivery in orthopedics.