Holmium-doped bioactive glass scaffolds for bone cancer treatment

Bone can be affected by tumours, thus being subjected to alteration of its physiological structure with possible negative impact on its mechanical resistance. Brachytherapy has proven to be a very advantageous technique to destroy cancer because it allows a high dose of radiation to be safely delivered into the tumour, minimizing the damage to adjacent healthy tissue. Bioactive glass (BG) scaffolds are particularly interesting devices for brachytherapy due to their ability to carry out the therapeutic action in situ and support bone tissue ingrowth after the treatment. One of the most popular techniques for producing BG scaffolds is the foam replica method, which allows obtaining highly porous and interconnected 3D bone-like scaffolds. After providing a comprehensive review of the state of the art in such fields, this experimental work aimed at developing BG scaffolds containing holmium (Ho) for the treatment of bone cancer by brachytherapy. Holmium-166 (166Ho), obtained from holmium-165 (165Ho) by neutron activation, has suitable physical properties for brachytherapy. A few compositions of BGs containing holmium have been already produced by some research teams but no example of BG scaffold containing holmium has been reported to date. Ho-doped BG (Ho-BG) was produced by sol-gel process at Federal University of ABC (São Paulo, Brazil). Thermal analysis, such as Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and Derivative Thermogravimetry (DTG) were performed on the dry gel powders in order to investigate the gel behaviour under heat treatment. In addition, Neutron Activation Analysis (NAA) and Fourier-Transform Infrared Spectroscopy (FTIR) were performed on the Ho-BG powders in order to evaluate the composition and structure of the glass, respectively. Since the particle size analysis showed the heterogeneity of the particle size, the glass powders were ground and sieved by using a sieve with mesh of 32 µm in diameter. The resulting powders, named Ho-BG32 powders, exhibited diameters below 32 µm, as expected. Differential Thermal Analysis (DTA) and Hot Stage Microscopy (HSM) were performed both on Ho-BG powders and Ho-BG32 powders in order to determine glass transition, crystallization onset, melting temperature, as well as first shrinkage and maximum shrinkage temperatures. X-Ray Diffraction (XRD), performed both on Ho-BG powders and Ho-BG32 powders, confirmed the amorphous nature of the material. Ho-BG powders were analysed by Scanning Electron Microscopy (SEM) and Energy Dispersive Spectrometry (EDS) in order to investigate powders morphology and their composition, respectively. The nanoporous texture and the surface area both of Ho-BG powders and Ho-BG32 powders were investigated by N2 sorption measurements and BET analysis. Once the powder characterization was completed, scaffolds were fabricated by foam replica method. Morphological and compositional analyses were performed in order to evaluate the potential suitability of these devices for bone replacement and regeneration. The scaffolds exhibited a total porosity of 86%. The pores were well interconnected and showed a bimodal size distribution. However, the scaffolds exhibited high brittleness. Therefore, the fabrication process should be optimized in order to obtain more resistant scaffolds. Moreover, additional in vitro/in vivo studies deserve to be carried out in order to verify the suitability of these scaffolds for the intended purpose.