Time‐Dependent Photothermal Modulation on Electroactive Gr/PVTF Composite Films for Enhancing Bone Regeneration

Time-dependent modulation of macrophage polarization and effective promotion of osteogenesis are essential for enhancing bone regeneration. This study designed composite films based on graphene nanosheets (Gr) and poly(vinylidene fluoride-trifluoroethylene) (PVTF), which can simultaneously provide surface potential and photothermal stimulation. The 0.3 wt.% Gr content not only delivered photothermal properties, but also improved the crystalline and piezoelectric properties of PVTF. The electrically polarized composite film with the d33 of -22 pC N^-1 achieved the optimal osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under appropriate illumination parameters. Meanwhile, the surface potential of the composite film can promote both M1 and M2 polarization of macrophages, which can be transformed to significant M2 polarization after photothermal stimulation, showing the potential for temporal modulation of macrophage polarization. Selective activation of heat shock proteins 47 (Hsp47) and 70 (Hsp70) is shown to be critical for the above modulation. In the cranial defect healing model, surface potential and photothermal stimulation of the Gr/PVTF composite films can synergistically result in optimal bone regeneration, implying its potential application in the field of tissue regeneration. This work not only provides a new method for enhancing bone regeneration, but also delivers new insights into the modulation of cell behaviors through multiple physical cues.