A 3D-printed bioactive glass scaffold coated with sustained-release PLGA/simvastatin stimulates calvarial bone repair

Abstract

To overcome the limited application forms and inadequate therapeutic effects of 3D-printed scaffolds and osteogenic drug carriers. Nonetheless, concerns persist regarding the negative effects of burst and nonsustained release. In this study, we further enhanced the osteoinductive potential of 3D-printed BAG scaffolds by coating them with simvastatin (SIM) and poly(lactic-co-glycolic acid) (PLGA) with sustained release properties. Morphological assessment through SEM revealed evenly coated 3D-printed BAG scaffolds (BAG/PLGA/SIM), which showed sustained SIM release properties in vitro. The SIM released from BAG/PLGA/SIM still exhibited osteogenic activity in the augmentation of ALP activity and mineralization in mesenchymal stem cells. In an animal study of rat calvarial bone defects, both SIM-loaded BAG scaffolds, BAG/PLGA/SIM and BAG/PLGA/5 × SIM, significantly improved bone regeneration. Moreover, the IHC analysis of BMP2 and vWF expression also exhibited significant increases in both SIM-loaded BAG scaffolds. Notably, a higher SIM concentration (BAG/PLGA/5 × SIM) did not outperform a lower SIM concentration (BAG/PLGA/SIM) in promoting new bone formation. In conclusion, BAG/PLGA/SIM scaffolds could provide an excellent 3D architecture with sustained SIM release properties in vitro and excellent osteogenic properties for bone repair in vivo. The drug-loading method on 3D-printed BAG scaffolds could provide an alternative strategy for the development of multifunctional scaffolds for clinical applications.

Keywords

• 3D scaffold
• Drug carrier
• Bioactive glass
• Simvastatin
• Sustained drug release