Fabrication and characterization of magnetic scaffold for bone tissue engineering.

The burden of cancer affects millions of people worldwide every year. Bone cancer, in particular, is characterized by aggressive growth and great suffering for the patients. Conventional therapies, such as surgery, chemotherapy, or radiotherapy, may cause significant side effects and part of cancerous tissue might not be completely removed, causing recurrence. Moreover, surgical removal of bone cancer can leave critical bone defects, requiring the use of a bone graft. Recently, hyperthermia has emerged as a possible alternative. This therapy takes advantage of the higher sensitivity to heat of cancer cells to destroy them by locally increasing the temperature in the range 41-45 °C, causing molecular and cellular alterations which end up in cell death. In particular, magnetic hyperthermia is considered a promising option, since it can reach bone structures in depth, it is non-invasive and more tissue specific. An alternating magnetic field heats up magnetic nanoparticles, converting electromagnetic waves into thermal energy. Superparamagnetic Iron Oxide Nanoparticles (SPIONS) are considered good candidates, since they do not have a residual magnetization and possess low toxicity profile. Bone tissue engineering is a growing field that aims at the development of bone substitutes, such as scaffolds, to repair damaged tissue. Bioactive glasses are good material candidates for their ability to create a strong bond with bone through the deposition of a hydroxyapatite layer on their surface. 1393B20 BAG overcomes the high crystallization tendency of traditional silicate glasses while promoting angiogenesis and osteogenesis in vitro and enhancing mineralization and collagen formation in vivo. This thesis’ work focused on the processing of multifunctional 3D printed scaffolds made of bioactive glass 1393B20 and SPIONS, with the aim of repairing critical bone defects of patients who underwent surgical removal of bone cancer and remove, at the same time, the residual cancer cells from the site. SPIONS were synthesized with the co-precipitation method and analyzed both as dry powder and liquid solution with TEM, which confirmed the success of their synthesis. 1393B20 BAG powder was combined with SPIONS and a binding agent in different ratio to produce an ink for robocasting. The rheological studies proved the suitability for printing for all the different inks, showing shear thinning behavior. The obtained 3D printed scaffolds were sintered and the impact of the SPIONS on the mechanical properties and bioactivity was assessed through compression test, in vitro dissolution in SBF, SEM and EDS analysis. A calorimetric test was performed to verify the heating capacity of the scaffolds when exposed to a magnetic field. Live and Dead and CyQuant assays analyzed the cytotoxicity of the material. From the obtained results, scaffolds proved to maintain their magnetic properties and increase their temperature under magnetic field exposure. Moreover, they showed promising results about their dissolution in SBF and bioactivity, with the deposition of a CaP HA-like layer. Nevertheless, further improvements are needed to enhance their mechanical properties, since they were not able to reach the ones of trabecular bone. Cell viability was assessed around the samples, but mild cytotoxicity was found in direct contact with the scaffolds, as confirmed by the poor cell proliferation quantification. Additional investigation is required to find new methods to improve biocompatibility for future clinical applications.