Hierarchical dual-porous hydroxyapatite doped dendritic mesoporous silica nanoparticles based scaffolds promote osteogenesis in vitro and in vivo

Biomaterial based scaffolds for treating large bone defects require excellent biocompatibility and osteoconductivity. Here we report on the fabrication of hydroxyapatite-dendritic mesoporous silica nanoparticles (HA-DMSN) based scaffolds with hierarchical micro-pores (5 µm) and nano-pores (6.4 nm), and their application for bone regeneration. The in vitro studies demonstrated good biocompatibility of dissolution extracts, as well as enhanced osteogenic potential indicated by dose-dependent upregulation of bone marker gene expression (osteocalcin gene (OCN), osteopontin gene (OPN), collagen type I alpha 1 gene (CoL1A1), runt-related transcription factor 2 gene (RUNX2), and integrin-binding sialoprotein gene (IBSP)), alkaline phosphatise (ALP) activity, and alizarin red staining. The in vivo studies showed that HA-DMSN scaffolds significantly increased bone formation in a rat cranial bone defect model after 4 weeks healing. Our study provides a simple method to fabricate promising inorganic scaffolds with hierarchical pores for bone tissue engineering. [graphic not available: see fulltext]