Switch-on mode of bioenergetic channels regulated by curcumin-loaded 3D composite scaffold to steer bone regeneration
Jianxu Wei, Xiaomeng Zhang, Zhuo Zhang, Xinxin Ding, Yuan Li, Yi Zhang, Xue Jiang, Hongbo Zhang, Hongchang Lai, Junyu Shi
Abstract
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 ([email protected]) 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 [email protected] is an ideal BTE material for stimulating rapid bone regeneration.