Lanthanum-doped mesoporous bioglasses/chitosan composite scaffolds enhance synchronous osteogenesis and angiogenesis for augmented osseous regeneration

With the progressive research of fabrication methodologies of biomaterials, hierarchically porous structures and bioactive compositions have been identified to promote bone repair and regeneration. In this study, we firstly fabricated lanthanum-doped bioglasses/chitosan (La-BGs/CS) composite scaffolds for novel bone tissue engineering materials. The La-BG microspheres in the scaffolds possessed hierarchically porous structures combining hollow cores and mesoporous shells. The effects of La-BGs/CS scaffolds on osteogenesis and angiogenesis were evaluated both in vitro and in vivo. The as-doped lanthanum oxide in the scaffolds remarkably promoted osteogenic differentiation of bone marrow-derived mesenchymal stem cells via activating ERK signaling pathway, and stimulated migration and tube formation of human umbilical vein endothelial cells. As compared with the BGs/CS scaffolds, the La dopants in the La-BGs/CS scaffolds contributed to higher expression levels of both osteogenic and angiogenic-related genes. Moreover, the mesopores and macropores within the La-BGs/CS scaffolds enhanced the osteoconductivity and stimulated bone regeneration in cranial defect model of rats. The La-BGs/CS scaffolds could also promote vascularization in vivo as demonstrated by Microfil perfusion, which further augmented osseous regeneration. Therefore, the La-BGs/CS scaffolds provide an admirable application and novel platform for bone tissue engineering.