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

Fecha de publicación: 01/10/2022

Autores de IIS La Fe

• Laia Tolosa Pardo

  Autor

• Jose Luis Gomez Ribelles

  Autor

• Gloria Gallego Ferrer

  Autor

Participantes ajenos a IIS La Fe

• Guillot-Ferriols, Maria
• Inmaculada Garcia-Briega, Maria
• Costa, Carlos M.
• Lanceros-Mendez, Senentxu

Grupos

• Hepatología experimental y Trasplante hepático

  Investigador Principal

  Laia Tolosa Pardo

• Unidad Mixta de Investigación en Hepatología Experimental

  

  Investigador Principal

  Ramiro Jover Atienza

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 beta-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.

Keywords

• mesenchymal stem cells; osteoblastogenesis; piezoelectricity; poly(vinylidene) fluoride; hydrogel