Magnetic Nanocomposite Scaffold-Induced Stimulation of Migration and Odontogenesis of Human Dental Pulp Cells through Integrin Signaling Pathways

Abstract

Magnetism is an intriguing physical cue that can alter the behaviors of a broad range of cells. Nanocomposite scaffolds that exhibit magnetic properties are thus considered useful 3D matrix for culture of cells and their fate control in repair and regeneration processes. Here we produced magnetic nanocomposite scaffolds made of magnetite nanoparticles (MNPs) and polycaprolactone (PCL), and the effects of the scaffolds on the adhesion, growth, migration and odontogenic differentiation of human dental pulp cells (HDPCs) were investigated. Furthermore, the associated signaling pathways were examined in order to elucidate the molecular mechanisms in the cellular events. The magnetic scaffolds incorporated with MNPs at varying concentrations (up to 10%wt) supported cellular adhesion and multiplication over 2 weeks, showing good viability. The cellular constructs in the nanocomposite scaffolds played significant roles in the stimulation of adhesion, migration and odontogenesis of HDPCs. Cells were shown to adhere to substantially higher number when affected by the magnetic scaffolds. Cell migration tested by in vitro wound closure model was significantly enhanced by the magnetic scaffolds. Furthermore, odontogenic differentiation of HDPCs, as assessed by the alkaline phosphatase activity, mRNA expressions of odontogenic markers (DMP-1, DSPP,osteocalcin, and ostepontin), and alizarin red staining, was significantly stimulated by the magnetic scaffolds. Signal transduction was analyzed by RT-PCR, Western blotting, and confocal microscopy. The magnetic scaffolds upregulated the integrin subunits (α1, α2, β1 and β3) and activated downstream pathways, such as FAK, paxillin, p38, ERK MAPK, and NF-κB. The current study reports for the first time the significant impact of magnetic scaffolds in stimulating HDPC behaviors, including cell migration and odontogenesis, implying the potential usefulness of the magnetic scaffolds for dentin-pulp tissue engineering.

Combination Design of Time-Dependent Magnetic Field and Magnetic Nanocomposites to Guide Cell Behavior

“…ALP activity, the mRNA expression of specific markers (e.g., osteocalcin and osteopontin) and alizarin red staining on nanocomposite scaffolds consisting of PCL and magnetite nanoparticles showed how magnetic features can stimulate the differentiation process [60]. The potential to upregulate specific integrin subunits and to activate downstream pathways (e.g., focal adhesion kinase-FAK, paxillin, p38, and ERK/MAPK) was reported [60].…”

Use of 0.4‐Tesla static magnetic field to promote reparative dentine formation of dental pulp stem cells through activation of p38 MAPK signalling pathway

“…Yun et al . () cultured human dental pulp cells on a magnetic nanocomposite scaffold and found that the scaffold enhanced the migration and dentinogenesis of cells via the phosphorylation of the p38 and ERK MAPK signalling pathways. Kwon et al .…”

Electrospun Nanofibers Applications in Dentistry

“…Collagen or PCL-gelatin-based nanofibrous scaffolds incorporating bioactive glass nanoparticles were developed for dentin-pulp regeneration and showed enhanced growth and odontogenic differentiation from human DPSCs compared to collagen nanofibrous scaffold via integrin-mediated process [5,49]. Magnetite nanoparticles were incorporated to PCL due to its intriguing physical cues that can tailor the behaviors of DPSCs [50]. The effects of these nanocomposite nanofibers on the adhesion, growth, migration, and odontogenic differentiation of human DPSCs were significantly remarkable compared to those of polymeric nanofibers.…”