3D-printed platform multi-loaded with bioactive, magnetic nanoparticles and an antibiotic for re-growing bone tissue

• Published in: International journal of pharmaceutics 2021-01, Vol.593, p.120097-120097, Article 120097
• Main Authors: Saraiva, Ana S., Ribeiro, Isabel A.C., Fernandes, Maria H., Cerdeira, Ana Cláudia, Vieira, Bruno J.C., Waerenborgh, João Carlos, Pereira, Laura C.J., Cláudio, Ricardo, Carmezim, Maria João, Gomes, Pedro, Gonçalves, Lídia M., Santos, Catarina F., Bettencourt, Ana F.
• Format: Article
• Language: English
• Subjects: Antibacterial; Bone regeneration; Iron oxide nanoparticles; Nanohydroxyapatite; Polylactic acid 3D-platform; Superparamagnetic
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.120097

[Display omitted] •Novel 3D-printed polylactic acid platform loaded with IONPs and HA was prepared.•The addition of minocycline assured anti- S. aureus 3D-platforms’ activity.•IONPs retain their magnetic properties in the 3D-platforms after cells incubation.•3D-platforms loaded with HA and IONPs increased cells’ osteogenic functionality. Polymeric platforms obtained by three-dimensional (3D) printing are becoming increasingly important as multifunctional therapeutic systems for bone treatment applications. In particularly, researchers aim to control bacterial biofilm on these 3D-platforms and enhance re-growing bone tissue, at the same time. This study aimed to fabricate a 3D-printed polylactic acid platform loaded with hydroxyapatite (HA), iron oxide nanoparticles (IONPs) and an antibiotic (minocycline) with tuneable properties and multistimuli response. IONPs were produced by a facile chemical co-precipitation method showing an average diameter between 11 and 15 nm and a superparamagnetic behaviour which was preserved when loaded into the 3D-platforms. The presence of two types of nanoparticles (IONPs and HA) modify the nanomorphological/nanotopographical feature of the 3D-platforms justifying their adequate bioactivity profile and in vitro cellular effects on immortalized and primary osteoblasts, including cytocompatibility and increased osteogenesis-related gene expression (RUNX2, BGLAP and SPP1). Disk diffusion assays and SEM analysis confirmed the effect of the 3D-platforms loaded with minocycline against Staphylococcus aureus. Altogether results showed that fabricated 3D-platforms combined the exact therapeutic antibiofilm dose of the antibiotic against S. aureus, with the enhanced osteogenic stimulation of the HA and IONPs nanoparticles which is a disruptive approach for bone targeting applications.