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

Bone repair materials for the effective treatment of bone defects should simultaneously possess excellent biocompatibility and promote osteogenic differentiation. Herein, we prepared pifithrin-alpha-loaded layered double hydroxide/chitosan (PFT alpha-LDH-CS) nanohybrid composites for the first time according to the following steps: (i) the immersion of LDH nanoplates and PFT alpha in a CS solution; and (ii) the self-assembly synthesis of PFT alpha-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 similar to 20 nm and width of similar to 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 PFT alpha. 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 PFT alpha-LDH-CS, suggesting that both samples had the desired cytocompatibility. Note that the PFT alpha released from the PFT alpha-LDH-CS rapidly improved the cell proliferation, ALP activity, ECM mineralization and protein level of the Runt-related transcription factor 2 (RUNX2) and beta-catenin. The enhanced osteogenic differentiation of hBMSCs on the PFT alpha-LDH-CS may be attributed to the PFTa released from the abovementioned nanohybrid composites, which resulted in the accumulation of beta-catenin and activation of the beta-catenin-mediated transcription activity in the cell nucleus. Therefore, the PFT alpha-LDH-CS nanohybrid composites with excellent cytocompatibility and enhanced osteoinductivity have great applications for novel bone repair materials.