Self-assembly of pifithrin-α-loaded layered double hydroxide/chitosan nanohybrid composites as a drug delivery system for bone repair materials

Abstract

Bone repair materials for the effective treatment of bone defects should simultaneously possess excellent biocompatibility and promote osteogenic differentiation. Herein, we prepared pifithrin-α-loaded layered double hydroxide/chitosan (PFTα–LDH–CS) nanohybrid composites for the first time according to the following steps: (i) the immersion of LDH nanoplates and PFTα in a CS solution; and (ii) the self-assembly synthesis of PFTα–LDH–CS nanohybrid composites after the pH value of the mixed solution was adjusted to 7.4. Interestingly, the LDH nanoplates with a thickness of ∼20 nm and width of ∼300 nm agglomerated together into flower-like shapes by self-assembly, and the CS was dispersed around the LDH nanoplates. The mesopores with the pore size of 3.95 nm among the LDH nanoplates served as channels for loading PFTα. Moreover, the CS around the LDH nanoplates increased the drug loading efficiency and drug sustained release property compared with the pure LDH nanoplates. The in vitro tests demonstrated that the human bone marrow-derived mesenchymal stem cells (hBMSCs) had good adhesion, spreading and proliferating on the LDH–CS and PFTα–LDH–CS, suggesting that both samples had the desired cytocompatibility. Note that the PFTα released from the PFTα–LDH–CS rapidly improved the cell proliferation, ALP activity, ECM mineralization and protein level of the Runt-related transcription factor 2 (RUNX2) and β-catenin. The enhanced osteogenic differentiation of hBMSCs on the PFTα–LDH–CS may be attributed to the PFTα released from the abovementioned nanohybrid composites, which resulted in the accumulation of β-catenin and activation of the β-catenin-mediated transcription activity in the cell nucleus. Therefore, the PFTα–LDH–CS nanohybrid composites with excellent cytocompatibility and enhanced osteoinductivity have great applications for novel bone repair materials.