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3D printed magnetic scaffolds for bone cancer theranostics and regeneration
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Atualmente, o cancro é a segunda maior causa de morte a nível mundial e, de acordo com a Organização Mundial da Saúde, a sua incidência e mortalidade tenderá a subir nas próximas décadas. Relativamente ao cancro ósseo, os tratamentos convencionais são a resseção tumoral por via cirúrgica, quimioterapia e radioterapia. Porém, a resseção pode resultar na criação de defeitos ósseos de tamanho crítico e, os dois últimos, revelam-se ineficientes para aplicações localizadas e provocam efeitos secundários indesejados.
Teragnóstico do cancro é uma abordagem que visa a criação de um sistema com capacidades de diagnóstico e terapia. Através da incorporação de nanopartículas superparamagnéticas de óxido de ferro (SPIONs) numa estrutura de suporte celular para regeneração óssea produzido por impressão 3D, é possível criar estruturas magnéticas personalizadas com aplicações potenciais no teragnóstico do cancro. Assim, esta dissertação tem como foco o desenvolvimento de estruturas magnéticas fabricadas por impressão 3D para aplicações de regeneração óssea e teragnóstico do cancro ósseo.
Por forma a obter estas estruturas, partículas de hidroxiapatite (HA) foram incorporação numa matriz polimérica de quitosano (CS) e álcool polivinílico (PVA), obtendo-se seis pastas com composições distintas. As pastas produzidas foram impressas usando a impressora 3D Zmorph VX adaptada e uma seringa de 10mL com uma agulha de calibre 18.
Além disto, duas suspensões de SPIONs distintas, não estabilizadas (NS) e estabilizadas com ácido oleico (OAS), foram adicionadas à pasta de CS/PVA/HA otimizada usando três concentrações (1,92, 3,77 e 5,54 wt.%). Os resultados obtidos indicam que as estruturas com 5,54 wt.% de NS SPIONs demonstraram uma melhor qualidade de impressão e retenção da forma do filamento, um maior gradiente de temperatura (7,5ºC) em ensaios de hipertermia magnética e boa bioatividade após 7 dias em SBF. Assim, estas estruturas revelaram-se como sendo as mais promissoras para aplicações de regeneração óssea e teragnóstico do cancro ósseo.
Cancer is currently the second leading cause of death worldwide and, according to the World Health Organization, it is expected to keep increasing in both incidence and mortality in the coming decades. Regarding bone cancer, the conventional treatments usually employ surgical tumour resection, chemotherapy, and radiotherapy. However, resection may result in critical-sized bone defects and the latter two prove inefficient for cancer cell targeting and lead to unwanted side effects. Cancer theranostics is a new approach which intends to deliver a system with both diagnostic and therapeutic capabilities. The incorporation of magnetic nanoparticles into additively manufactured bone regeneration scaffolds, enables the creation of tailored magnetic structures with potential applications for cancer theranostics. Therefore, the present study focuses on the development of 3D printed magnetic scaffolds for bone cancer theranostics and regeneration. To attain such structures, hydroxyapatite (HA) particles were integrated in a polymeric matrix composed of chitosan (CS) and poly(vinyl) alcohol (PVA), to form six pastes with varying compositions. These pastes were 3D printed using an adapted Zmorph VX 3D printer and a 10 mL syringe with an 18 G needle. Furthermore, two different superparamagnetic iron oxide nanoparticles (SPIONs) suspensions, non-stabilized (NS) and oleic acid stabilized (OAS), were added to the optimized CS/PVA/HA paste at three different concentrations (1.92, 3.77, and 5.54 wt.%). The obtained results indicate that the scaffolds containing 5.54 wt.% of NS SPIONs, which exhibit the best printability and shape fidelity, highest temperature gradient of 7.5 ºC in MHT testing, and good bioactivity after 7 days in SBF, were the most promising for applications in bone cancer theranostics and regeneration.
Cancer is currently the second leading cause of death worldwide and, according to the World Health Organization, it is expected to keep increasing in both incidence and mortality in the coming decades. Regarding bone cancer, the conventional treatments usually employ surgical tumour resection, chemotherapy, and radiotherapy. However, resection may result in critical-sized bone defects and the latter two prove inefficient for cancer cell targeting and lead to unwanted side effects. Cancer theranostics is a new approach which intends to deliver a system with both diagnostic and therapeutic capabilities. The incorporation of magnetic nanoparticles into additively manufactured bone regeneration scaffolds, enables the creation of tailored magnetic structures with potential applications for cancer theranostics. Therefore, the present study focuses on the development of 3D printed magnetic scaffolds for bone cancer theranostics and regeneration. To attain such structures, hydroxyapatite (HA) particles were integrated in a polymeric matrix composed of chitosan (CS) and poly(vinyl) alcohol (PVA), to form six pastes with varying compositions. These pastes were 3D printed using an adapted Zmorph VX 3D printer and a 10 mL syringe with an 18 G needle. Furthermore, two different superparamagnetic iron oxide nanoparticles (SPIONs) suspensions, non-stabilized (NS) and oleic acid stabilized (OAS), were added to the optimized CS/PVA/HA paste at three different concentrations (1.92, 3.77, and 5.54 wt.%). The obtained results indicate that the scaffolds containing 5.54 wt.% of NS SPIONs, which exhibit the best printability and shape fidelity, highest temperature gradient of 7.5 ºC in MHT testing, and good bioactivity after 7 days in SBF, were the most promising for applications in bone cancer theranostics and regeneration.
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3D printing additive manufacturing bone regeneration cancer theranostics chitosan hydroxyapatite