Electroactive Poly(Vinylidene Fluoride-Trifluoroethylene)-Zinc Oxide Nanorod Films for Macrophage Polarization Regulation.

Mimicking the nanotopographical and electrical characteristics of the native bone interface provides an effective strategy for designing biomimetic bone repair materials. In this study, a PVTF-ZNR composite film was developed to establish a coupled topographical-electrical biomimetic microenvironment by constructing low-exposure-height zinc oxide nanorod (ZNR) arrays on the surface of a poly(vinylidene fluoride-trifluoroethylene) (PVTF) electroactive film followed by electrical poling. The low-exposed ZNR structures provided bone-inspired nanoscale topographical cues and promoted the crystallization of the surrounding PVTF, while the poled PVTF matrix enabled tunable overall surface potentials and a stable ZNR/PVTF heterogeneous potential distribution. Biological evaluations showed that the introduction of surface nanostructures enhanced the interfacial responsiveness of bone marrow-derived macrophages (BMDMs), accompanied by the simultaneous upregulation of M1- and M2-related phenotypic markers and cytokines. Under positive poling, the larger positive surface potential change further suppressed pro-inflammatory signals and enhanced the secretion of anti-inflammatory and repair-related factors in highly activated BMDMs, leading to a more pronounced M2 phenotypic bias. Consequently, a pro-reparative osteoimmune microenvironment was established, which promoted the adhesion, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). These results indicate that the PVTF-ZNR composite film can regulate macrophage activation and phenotypic bias through the synergistic effects of nanotopographical cues and surface potential modulation. This work highlights the potential of coupled topographical-electrical biomimetic interfaces for osteoimmune microenvironment regulation during bone defect repair.