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.

Implant-associated infections are a severe concern affecting 1−3 % of patients undergoing primary joint arthroplasty [1]. Magnetic hyperthermia, which can be non-invasively induced by applying an alternating magnetic field (AMF) around a metallic implant, is a new approach with great potential. This research project explores the application of non-contact induction heating (IH) of metallic implants in orthopedic surgery. It focuses on the heating behavior of paramagnetic biomaterials relevant to this application in alternating magnetic fields.
Empirical testing plays an inherent role in research. However, it is often very time-consuming, especially when assessing many specimens. With in silico simulations, data can be yielded much faster. An analytical model simulating the heating dynamics of paramagnetic materials in the AMF was constructed to provide a tool for faster suitability assessment of metallic biomaterials for magnetic hyperthermia. The model was then compared with empirical data obtained in a controlled environment.

The empirical data showed a quadratically increasing temperature rise with the field amplitude and a linearly growing temperature rise with the frequency. The constructed analytical model confirmed that the heat generated in the materials increases quadratically with the increasing AMF amplitude. Additionally, increasing the frequency of the AMF also affects heat generation. The model predicted different trends depending on what domain a material is assigned to. However, empirical data indicates a consistent linear relationship across several assessed frequencies and materials.

Based on the obtained knowledge of the material's behavior in AMF, a new hip implant intended for magnetic hyperthermia treatment was designed. It utilized a coating on the neck of the femoral stem, designed to enable targeted IH, particularly to regions most susceptible to bacterial infections. The experiment featured a multi-material specimen consisting of Ti Gr. 23 and ST. 37, which mimicked the neck of a hip implant, the proof of concept was successfully demonstrated, showing a significant temperature increase for specimens with coating compared to the ones without at high magnetic field strength and frequency. However, targeted IH was not detected.

Better computational models can further explore the obtained knowledge, and the proof-of-concept can be further tested to investigate its contribution to treating resistant bacterial biofilms.

This thesis addresses infection risks associated with orthopedic implants and focuses on challenges associated with tackling bacterial biofilms comprising antibiotic resistant organisms. Here, a proof-of-concept drug delivery system for prevention of implant-associated infections is presented. The aim of this study was to characterize two materials, PluronicF108andF127, by evaluating their physical and drug releasing properties to develop a controllable, thermosensitive on-demand drug delivery. The two hydrogels were characterized in terms of their rheological and micelle forming properties at various concentrations, using the inverted tube test and dynamic light scattering, respectively. Their stability was assessed by recording the weight loss ratio of the hydrogel and the drug release characteristics were assessed by monitoring the release of a hydrophobic dye. The cytotoxicity of the system was also tested in vitro.

The rheological assessment showed that the lower sol-gel temperature was in the range of 20-35◦ C and the upper gel-sol transition was in the range of 45-65◦ C, depending on the mass fraction concentration, hydrophilicity and the type of solvent. Furthermore, these characteristics also influence the critical micellar concentration, stability and therefore their release. The most stable hydrogel com position was 20 wt% Pluronic F127 in 1x phosphate-buffered saline (PBS). This study demonstrated a proof-of-concept of an on-demand drug releasing system com prising Pluronic F127 and polycaprolactone (PCL) as thermoresponsive components. The system showed that it can be used for single as well as intermittent release. Increasing the stability of the Pluronic, however, is further desirable. The system offers a non-invasive approach for an on-demand drug delivery. It requires, however, further work to enhance stability of the hydrogel to minimize passive release.