Switch-on mode of bioenergetic channels regulated by curcumin-loaded 3D composite scaffold to steer bone regeneration

Metabolic energy to steer osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) could be a promising therapeutic target for bone tissue engineering (BTE), but prior knowledge of this issue is limited. To address bone defects with BTE, we customized a three-dimensional (3D)-printed composite scaffold (Cur@MS) to allow the controlled release of curcumin, which could facilitate the “switch-on” mode of Glucose transporter 1 (GLUT1) in BMSCs. Consequently, bioenergetic channels, i.e. glucose uptake, were “switched on” to activate GLUT1-RUNX2 crosstalk, which was closely orchestrated with bone regeneration. Furthermore, curcumin-induced cholesterol/lipid raft (Cho/LR) was a “sensor” to trigger the “switch” (GLUT1) by directing its spatial distribution into clusters. In contrast, selective inhibition of Cho/LR and GLUT1 led to a “switch-off” mode and compromised bone regeneration in vivo. Overall, the results suggest Cho/LR is a potential target to steer BMSCs and Cur@MS is an ideal BTE material for stimulating rapid bone regeneration.