Manipulation of Heterogeneous Surface Electric Potential Promotes Osteogenesis by Strengthening RGD Peptide Binding and Cellular Mechanosensing

Abstract

The heterogeneity of extracellular matrix (ECM) topology, stiffness, and architecture is a key factor modulating cellular behavior and osteogenesis. However, the effects of heterogeneous ECM electric potential at the micro‐ and nanoscale on osteogenesis remain to be elucidated. Here, the heterogeneous distribution of surface potential is established by incorporating ferroelectric BaTiO3 nanofibers (BTNF) into poly(vinylidene fluoridetrifluoroethylene) (P(VDF‐TrFE)) matrix based on phase‐field and first‐principles simulation. By optimizing the aspect ratios of BTNF fillers, the anisotropic distribution of surface potential on BTNF/P(VDF‐TrFE) nanocomposite membranes can be achieved by strong spontaneous electric polarization of BTNF fillers. These results indicate that heterogeneous surface potential distribution leads to a meshwork pattern of fibronectin (FN) aggregation, which increased FN‐III7‐10 (FN fragment) focal flexibility and anchor points as predicted by molecular dynamics simulation. Furthermore, integrin clustering, focal adhesion formation, cell spreading, and adhesion are enhanced sequentially. Increased traction of actin fibers amplifies mechanotransduction by promoting nuclear translocation of YAP/Runx2, which enhances osteogenesis in vitro and bone regeneration in vivo. The work thus provides fundamental insights into the biological effects of surface potential heterogeneity at the micro‐ and nanoscale on osteogenesis, and also develops a new strategy to optimize the performance of electroactive biomaterials for tissue regenerative therapies.

Accelerated Bone Regeneration on the Metal Surface through Controllable Surface Potential

“…30 For example, it was reported that heterogeneous surface potential combined with topological structure affected osteogenesis under the condition of keeping the same other properties. 31 In this study, the metal surface provided a different and tailorable surface potential while keeping other factors almost the same, owing to the ferroelectricity of poled PVTF, which was biocompatible and piezoelectrical. 32−34 Moreover, the introduction of PVTF could further develop a piezoelectric material-based strategy to physically stimulate a single source of biomedical metals for osteogenic differentiation in vitro and bone regeneration in vivo.…”

Nano-Topographically Guided, Biomineralized, 3D-Printed Polycaprolactone Scaffolds with Urine-Derived Stem Cells for Promoting Bone Regeneration

“…In addition, the water contact angle of NMS was significantly lower than that of MS, which indicated the greater existence of mineralized substances deposited onto the scaffolds. In the field of bone repair, the surface charge of biological scaffolds plays an important role in regulating various cell behaviors [ 43 , 44 ]. The Zeta potential of BS, NS, MS, and NMS was −49.44 ± 3.75 mV, 58.35 ± 4.04 mV, 43.37 ± 3.15 mV, and −18.71 ± 3.57 mV at a pH of 7.4, respectively.…”

The role of smart polymeric biomaterials in bone regeneration: a review

“…(B) Thermo-responsive polymers: Schematic illustration of the fabrication of CSP‐LB hydrogel, enhanced mechanical and biological properties ( Lv et al, 2023 ). (C) Electrically-responsive polymers: Porous poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and calcium phosphate (CaP) coatings created the scaffold (left); Barium titanate (BTO)/polyvinylidene fluoride–trifluoroethylene (P(VDF‐TrFE)) accelerate bone regeneration (right) ( Ma Z. et al, 2023 ; Bai et al, 2023 ). (D) Enzyme-responsive polymers: MMP-induced BMP-2 release for fracture healing ( Deng et al, 2020 ).…”

“…Other notable developments include a 3D polyurethane foam (PUF) scaffold coated with piezoelectric PVDF-HFP and mineralized calcium phosphate (CaP), which stimulated osteogenic cell differentiation and in vivo ectopic bone formation due to its components’ synergistic effects ( Ma et al, 2023a ). BaTiO 3 nanofibers (BTNF) integrated into a poly (vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix created an anisotropic surface potential, bolstering mechanotransduction, in vitro osteogenesis, and in vivo bone regeneration as shown in Figure 1C ( Bai et al, 2023 ). Wang et al (2023) suggested a composite scaffold consisting of piezoelectric Whitlockite (WH) and polycaprolactone (PCL) that fostered neurovascularized bone tissue regeneration through sustained Mg 2+ release.…”