Magnetic biomaterials are multifunctional tools currently under investigation as theranostic platforms for biomedical applications. They can be implanted in bone tissue after bone cancer resection to perform local interstitial hyperthermia treatment. Given the requirements of high quality treatment, the hyperthermia therapy should be performed monitoring the system temperature, to avoid hot spots and control the treatment outcome. It is known that the magnetic properties of such implants vary with temperature. It is hypotesized that the treatment dynamic could be monitored using a microwave monitoring system. The variation of the electromagnetic properties of the biological tissues and the magnetic implant during the therapy would result in a different propagation of the microwave signal. This work investigates the feasibility of using microwaves to non-invasively monitor hyperthermia treatments with a simplified monodimensional propagation model. The forward problem is solved to identify the working frequencies, the matching medium properties and study several candidate materials. By using the numerical solutions from nonlinear and multiphysics simulations of the bone tumor hyperthermia treatment using magnetic scaffolds, the microwave signal propagation dynamic is studied. From our feasibility analysis, we found that it is possible to correlate the average tumor temperature with significant (~20 dB) variations in the transmission coefficient during a typical interstitial hyperthermia session using magnetic scaffolds. Our work brings together, for the first time, the electromagnetic material properties, the physio-pathology and physics of the hyperthermia treatment and the microwave propagation problem, thus paving the route for the development of an innovative theranostic system.

Magnetic bone substitutes are multifunctional nanocomposite biomaterials designed to serve as an in situ attraction platform for magnetic carriers of growth factors. The morphological and functional properties of these biomaterials were characterized so far, but very little is known on the treatment dynamics, and the latter cannot be designed from an engineering point of view. For the first time, this work deals with the mathematical modeling of the use of magnetic scaffolds and functionalized nanoparticles to evaluate the enhancement of osteogenesis and bone repair. The non-linear magnetization of the scaffolds is considered to simulate the attraction and transport of magnetic nanoparticles. Different biomaterials and drug carriers from the literature are analyzed. The drug release via RF-heating is modeled considering the multiphysics nature of the phenomena. The physiological process of bone healing is reproduced using nine non-linear equations. The influence of the delivered growth factor on osteogenesis is assessed and quantified in silico, while compared to numerical simulations of intravenous injection of growth factor and to its release from the biomaterial. The exploitation of magnetic carriers of biomolecules with magnetic scaffolds allows to produce a more homogeneous and uniform distribution of mature bone, overcoming the limitation of traditional drug delivery techniques.

Magnetic scaffolds have been investigated as promising tools for the interstitial hyperthermia treatment of bone cancers, to control local recurrence by enhancing radio- and chemotherapy effectiveness. The potential of magnetic scaffolds motivates the development of production strategies enabling tunability of the resulting magnetic properties. Within this framework, deposition and drop-casting of magnetic nanoparticles on suitable scaffolds offer advantages such as ease of production and high loading, although these approaches are often associated with a non-uniform final spatial distribution of nanoparticles in the biomaterial. The implications and the influences of nanoparticle distribution on the final therapeutic application have not yet been investigated thoroughly. In this work, poly-caprolactone scaffolds are magnetized by loading them with synthetic magnetic nanoparticles through a drop-casting deposition and tuned to obtain different distributions of magnetic nanoparticles in the biomaterial. The physicochemical properties of the magnetic scaffolds are analyzed. The microstructure and the morphological alterations due to the reworked drop-casting process are evaluated and correlated to static magnetic measurements. THz tomography is used as an investigation technique to derive the spatial distribution of nanoparticles. Finally, in silico multiphysics experiments are used to investigate the influence on the loading patterns on the interstitial bone tumor hyperthermia treatment.