Magnetically Activated Piezoelectric 3D Platform Based on Poly(Vinylidene) Fluoride Microspheres for Osteogenic Differentiation of Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) osteogenic commitment before injection enhances bone regeneration therapy results. Piezoelectric stimulation may be an effective cue to promote MSCs pre-differentiation, and poly(vinylidene) fluoride (PVDF) cell culture supports, when combined with CoFe2O4 (CFO), offer a wireless in vitro stimulation strategy. Under an external magnetic field, CFO shift and magnetostriction deform the polymer matrix varying the polymer surface charge due to the piezoelectric effect. To test the effect of piezoelectric stimulation on MSCs, our approach is based on a gelatin hydrogel with embedded MSCs and PVDF-CFO electroactive microspheres. Microspheres were produced by electrospray technique, favouring CFO incorporation, crystallisation in β-phase (85 %) and a crystallinity degree of around 55 %. The absence of cytotoxicity of the 3D construct was confirmed 24 h after cell encapsulation. Cells were viable, evenly distributed in the hydrogel matrix and surrounded by microspheres, allowing local stimulation. Hydrogels were stimulated using a magnetic bioreactor, and no significant changes were observed in MSCs proliferation in the short or long term. Nevertheless, piezoelectric stimulation upregulated RUNX2 expression after 7 days, indicating the activation of the osteogenic differentiation pathway. These results open the door for optimising a stimulation protocol allowing the application of the magnetically activated 3D electroactive cell culture support for MSCs pre-differentiation before transplantation.

Exosome‐Hydrogel System in Bone Tissue Engineering: A Promising Therapeutic Strategy

“…This study initially demonstrated the low cytotoxicity of this magnetoelectrically re-sponsive hydrogel to MC3T3-E1 cells inoculated on the surface of the material. Guillot-Ferriols et al [89] prepared a composite gelatin hydrogel encapsulating CoFe 2 O 4 /PVDF electroactive microspheres, which produced a piezoelectric stimulation response to internal BMSCs under the action of a magnetic field and significantly stimulated the proliferation and osteogenic differentiation of BMSCs. However, research on magnetoelectric materials is still in the exploratory stage, and there are some problems to be overcome, such as cytotoxicity, and the influence of piezoelectric stimulation on exosomes is unknown.…”

Materials‐Mediated In Situ Physical Cues for Bone Regeneration

“…[214] These changes are beneficial in achieving the desired magnetomechanical/electrical response of the scaffold and CFO was thus incorporated into the matrix of piezoelectric polymers. [215] CFO/P(VDF-TrFE) coatings containing CFO with a mass fraction of 6% improved osteogenic differentiation of MC3T3-E1 cells under an SMF condition. [216] Moreover, a type of magnetoactive 3D porous scaffold comprised of PVDF and CFO was found to exert both local magnetomechanical and magnetoelectric response, thereby significantly promoting the proliferation of pre-osteoblasts through the application of magnetic stimuli.…”