RF Modeling, Design, Characterization and Biomedical Applications of Magnetic Scaffolds

LODI, MATTEO BRUNO

2022-04-20

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Abstract

Multifunctional, stimuli-responsive theranostic biomaterials are gaining attention from the scientific community for their use as versatile, complete platforms in contemporary biomedicine. By combining magnetic nanoparticles and bioceramic, polymeric or composite biomaterials, a magnetic implants or scaffold (MagS), which can be remotely controlled by static or dynamic magnetic fields, can be manufactured. To date, a plethora of MagS have been developed, characterized and tested for tissue engineering, drug delivery and for the hyperthermia treatment of tumors. In particular, bone tumors could be treated with MagS by performing radiofrequency local and interstitial hyperthermia. Furthermore, MagS allow to repair the healed tissue also ensuring drug delivery of magnetic carriers of growth factors. Despite the promising potential, quantitative, engineered and application-driven rules or models for designing MagS have not been provided yet. In this work, we focused on the theoretical and numerical modeling of the hyperthermia treatment of bone cancers by using magnetic scaffolds. We proposed a Cole-Cole model for describing the magnetic susceptibility spectra and investigate the heat dissipation of MagS. A nonlinear, multiphysics electromagneto-thermal model was developed and used to investigate the treatment planning of bone tumors with MagS. The proposed numerical framework allows to properly setup the extrinsic treatment parameters to perform an effective treatment in different physiopathological conditions. Furthermore, the in silico findings highlighted that manufacturing nonlinearities and geometric aspects can be relevant to the hyperthermic potential of MagS. Therefore, we designed and characterized polymeric scaffolds loaded with magnetic nanocrystals by a drop-casting procedure to control the pattern. By combining static magnetic measurements, thermogravimetric analysis and THz tomography, advanced simulations were carried out to assess how the loading patterns of MagS can influence the outcome of the hyperthermia treatment. The evaluation of the specific absorption rate (SAR) of MagS is a crucial aspect. By using a commercial ferromagnetic polymer, we 3D-printed MagS with biomimetic architecture and performed calorimetric measurements in air, de-ionized water and agar environment, to develop a reliable and robust protocol to estimate the SAR. The possibility of using MagS as core element of a magnetic drug delivery system was investigated by developing a novel nonlinear, multiphysics model for account the targeting of nanocarriers of growth factor with static magnetic fields, how to trigger the release of the biomolecule with radiofrequency heating and accelerate the bone tissue healing. Finally, the feasibility of using microwave to non-invasively monitor hyperthermia treatment was investigated with a simplified monodimensional model. This thesis work can foster the development of innovative theranostic modalities using MagS.