Icariin doped bioactive glasses seeded with rat adipose-derived stem cells to promote bone repair via enhanced osteogenic and angiogenic activities

Abstract

Aims: Cell communication between mesenchymal stem cells and blood vessel cells are crucial for bone repair. We have previously shown that the phyto-molecule icariin significantly promoted osteogenic differentiation of rat adipose-derived stem cells (ASCs). In the present study, we aimed to investigate the relationship between icariin induced osteogenic differentiation of ASCs and angiogenesis of rat endothelial progenitor cells (EPCs). Besides, we used icariin doped 45S5 Bioglass seeded with ASCs to promote bone healing in rat calvarial bone defect models.

Main methods: The conditioned medium from undifferentiated ASCs (ASCs-CM) and icariin induced ASCs (Icariin-ASCs-CM) was obtained and the vascular endothelial growth factor (VEGF) protein secretion level was measured. The angiogenic capacity and molecular mechanism of ASC-CM and Icariin-ASCs-CM on rat EPCs was analyzed. Rat calvarial bone defect models were established and treated with scaffolds implantation. Micro-CT imaging, histological and immunohistological staining were performed on the isolated specimens at 12 weeks post-surgery.

Key findings: VEGF protein expression was significantly increased after icariin treatment with the highest expression in the 10^-7 M icariin group. Icariin-ASCs-CM obviously increased the angiogenesis of rat EPCs and this capacity was inhibited by a VEGF/VEGF receptor-specific binding inhibitor bevacizumab. Results of the in vivo investigations showed that all scaffolds promoted bone healing compared to the Control group. Icariin significantly improved the healing capacity of 45S5 Bioglass seeded with ASCs.

Significance: Implantation of Icariin/45S5 Bioglass seeded with rat ASCs could obviously promote both osteogenesis and angiogenesis and therefore represents an ideal candidate bone substitutes for bone repair and regeneration.

Keywords: 45S5 Bioglass; Adipose-derived stem cells; Angiogenesis; Bone repair and regeneration; Icariin; Vascular endothelial growth factor.