Silicon-Enhanced Adipogenesis and Angiogenesis for Vascularized Adipose Tissue Engineering

Abstract

The enhancement of adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and sufficient vascularization remain great challenges for the successful reconstruction of engineered adipose tissue. Here, the bioactive effects of silicon (Si) ions on adipogenic differentiation of human BMSCs (HBMSCs) and the stimulation of vascularization during adipose tissue regeneration are reported. The results show that Si ions can enhance adipogenic differentiation of HBMSCs through the stimulation of the expression of adipogenic differentiation switches such as peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α. Furthermore, Si ions can enhance both angiogenesis and adipogenesis, and inhibit dedifferentiation of cocultured adipocytes by regulating the interactions between HBMSC-derived adipocytes and human umbilical vein endothelial cells, in which the promotion of the expression of insulin-like growth factor 1 and vascular endothelial growth factor plays vital roles. The in vivo studies further demonstrate that the designed composite hydrogel with the ability to release bioactive Si ions clearly stimulates neovascularization and adipose tissue regeneration. The study suggests that Si ions released from biomaterials are important chemical cues for adipogenic differentiation and biomaterials with the ability to release Si ions can be designed for adipose tissue engineering.