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Polylactic acid 3D scaffolds as platforms for local-delivery and hyperthermia applications in bone tumours
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The bone is one of the most frequent target sites of metastases. Presently, treatment management has a variety of limitations that need to be replaced by more effective strategies. In this context, three-dimensional (3D) printed scaffolds can be an adjuvant local therapy for bone metastases as well as accomplish several biological and mechanical requirements for bone regeneration with the additional possibility of design the architecture of the scaffold according to the patient’s needs. In this study, 3D-printed PLA scaffolds were multifunctionalized with: i) collagen (Col) and hydroxyapatite nanoparticles (nHA) aiming the promotion of bone regeneration, ii) magnetic nanoparticles (MNs) for magnetic hyperthermia purposes against bone tumour cells and iii) minocycline (MH) to prevent bone infection. The physicochemical properties, in vitro swelling ability, drug (MH) release, bioactivity, magnetic heating properties, antimicrobial properties and cell response of functionalized PLA scaffolds were investigated. Results showed that scaffolds were obtained with uniform square macroporous and a stable functionalization. Also, a properly low swelling ability for bone regeneration and bioactive properties specially with the presence of nHA was attained. MH functionalization resulted into an efficient antibacterial activity against Staphylococcus aureus, a pathogen often associated with bone-related infections, that was coupled with an adequate drug release profile leading to an effective prevention of bone infection. PLA scaffolds revealed to be no cytotoxic for cells (MG-63 osteoblasts) and had a higher osteogenic potential when loaded with nHA. SPIONs demonstrated magnetic heating ability, however at the tested concentrations did not reached hyperthermia temperatures (40-45ºC). Therefore, multifunctionalized 3D printed PLA scaffolds showed to be a promising strategy for bone regeneration associated with infection prevention and bone cancer treatment with the need to improve on the magnet heating ability of MNs to advance bone tumours management.
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Palavras-chave
Bone cancer Bone regeneration Polylactic acid (PLA) magnetic nanoparticles Hydroxyapatite nanoparticles Magnetic hyperthermia