Bioinspired fabrication of carbonated hydroxyapatite/chitosan nanohybrid scaffolds loaded with TWS119 for bone regeneration

Effective repair of bone defects mainly depends on the osteoinductivity and biocompatibility of implants. Herein, we for the first time reported the bioinspired fabrication of carbonated hydroxyapatite/chitosan (CHA/CS) nanohybrid scaffolds using CaCO 3 /CS porous scaffolds as sacrificial templates, followed by loading TWS119 drugs (CHA/CS/TWS119). After treatment with phosphate buffer solutions, the CaCO 3 /CS porous scaffolds were in situ converted into CHA/CS nanohybrid scaffolds via the dissolution-precipitation reaction. The as-formed CHA nanoplates with thicknesses of ∼20 nm and widths of 1.0–2.0 μm were perpendicular to the scaffold surfaces. The three-dimensional interconnected macropores supported the adhesion and spreading of bone mesenchymal stem cells (BMSCs), and the mesopores within the CHA nanoplates as drug delivery channels improved the drug loading-release properties. The controlled drug release of the CHA/CS/TWS119 nanohybrid scaffolds significantly enhanced the osteogenic differentiation of BMSCs by the activated GSK3β/β-catenin pathway. Moreover, rat cranial defect models revealed the enhancing effects of the CHA/CS/TWS119 scaffold on bone tissue regeneration. The micro-CT, haematoxylin and eosin (H&E) staining, Van Gieson (VG) staining, Masson staining and double fluorochrome labelling results demonstrated that more new bone tissues were formed in the CHA/CS/TWS119 nanohybrid scaffolds than the control group without loading TWS119. Therefore, the CHA/CS/TWS119 nanohybrid scaffold is a promising therapeutic material for bone tissue regeneration.