Subcutaneous osteochondral regeneration using a bilayer scaffold by leveraging angiogenic activities

Bone marrow stem cell (BMSC) therapy is a promising method to achieve subcutaneous osteochondral regeneration. However, it remains obscure due to the incorrect angiogenic niche. Studies have demonstrated that an antiangiogenic niche promotes cartilage regeneration, whereas a proangiogenic niche facilitates bone formation. Considering that curcumin (Cur) is an antiangiogenic drug and Danshen (DS) is a proangiogenic drug, this study is the first to develop a gelatin-based bilayer porous scaffold, where curcumin-loaded gelatin (Cur/GT) was used as the upper layer and DanShen-loaded gelatin (DS/GT) was used as the bottom layer. The data revealed that both Cur and DS could be sustained and released from Cur/GT and DS/GT, respectively. When cocultured with human umbilical vein endothelial cells, Cur/GT inhibited tube formation, whereas DS/GT promoted tube formation. Furthermore, the findings demonstrated that the Cur addition in the upper layer exerted antiangiogenic activity to the stable chondrogenesis of BMSCs, the DS addition in the bottom layer endowed proangiogenic effects to promote osteogenesis of BMSCs, and the bilayer scaffold successfully achieved subcutaneous osteochondral regeneration when recolonized with BMSCs. This study provides new insight into subcutaneous osteochondral regeneration by leveraging the angiogenic microenvironment.