Bone Piezoelectricity-Mimicking Nanocomposite Membranes Enhance Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Amplifying Cell Adhesion and Actin Cytoskeleton

Ferroelectric biomaterials have been widely investigated and demonstrated to enhance osteogenesis by simulating the inherent electrical properties of bone tissues. Nevertheless, the underlying biological processes are still not wellunderstood. Hence, this study investigated the underlying biological processes by which bone piezoelectricity-mimicking barium titanate/poly(vinylidene fluoride-trifluoroethylene) nanocomposite membranes (BTO nanocomposite membranes) promote osteogenesis of Bone Marrow Mesenchymal Stem Cells (BMSCs). Ourresults revealed that the piezoelectric coefficient (d ₃₃) of nanocomposite membranes aftercontrolled corona poling was similar to that of native bone, and exhibited highly-stable piezoelectrical properties and concentrated surface electrical potential. These nanocomposite membranes significantly enhanced the adhesion and spreading of BMSCs, which was manifested as increased number and area of mature focal adhesions. Furthermore, the nanocomposite membranes significantly promoted the expression of integrin receptors genes (α1, α5 andβ3), which in turn enhanced osteogenesis of BMSCs, as manifested by upregulated Alkaline Phosphatase (ALP) and Bone Morphogenetic Protein 2 (BMP2) expression levels. Further investigations found that the Focal Adhesion Kinase (FAK)-Extracellular Signal-Regulated Kinase1/2 (ERK 1/2) signaling axis may be involved in the biological process of polarized nanocomposite membrane-induced osteogenesis. This study thus provides useful insights for betterunderstanding of the biological processes by which piezoelectric or ferroelectric biomaterials promote osteogenesis.