Effects of the PI3K/Akt signaling pathway on the hair inductivity of human dermal papilla cells in hair beads.

Dermal papilla cells (DPCs), which play a central role in the regulation of hair follicle development and hair growth, are among the most promising cell sources for hair regenerative medicine. However, a critical issue in the use of DPCs is the immediate loss of hair inducing functions in typical two-dimensional (2D) culture. We have previously demonstrated that when DPCs are encapsulated in drops of collagen gel (named hair beads, HBs), the density of collagen and cells is concentrated >10-fold during 3 d of culture through the spontaneous constriction of the drops, leading to efficient hair follicle regeneration upon transplantation. However, the mechanisms responsible for the activation of the hair-inducing functions of DPCs have been poorly elucidated. Here, transcriptome comparisons of human DPCs in HB culture and in typical 2D culture revealed that the phosphoinositide 3-kinase and Akt (PI3K/Akt) signaling pathway was significantly upregulated in HB culture. Inhibition of the PI3K/Akt signaling pathway decreased the hair-inducing capability of DPCs in HBs, while the activation of the PI3K/Akt signaling pathway using an activator improved trichogenous gene expression of DPCs in 2D culture. These results suggest that the PI3K/Akt signaling pathway is crucial for the maintenance and restoration of hair inductivity of DPCs. HB culture and/or activators of the PI3K/Akt signaling pathway could be a promising strategy for preparing DPCs for hair regenerative medicine.

Direct Wiring of Liquid Metal on an Ultrasoft Substrate Using a Polyvinyl Alcohol Lift-off Method.

In recent years, wiring and system construction on ultrasoft materials such as biological tissues and hydrogels have been proposed for advanced wearable devices, implantable devices, and soft robotics. Among the soft conductive materials, Ga-based liquid metals (LMs) are both biocompatible and ultrasoft, making them a good match for electrodes on the ultrasoft substrates. However, gels and tissues are softer and less wettable to the LMs than conventional soft substrates such as Ecoflex and polydimethylsiloxane. In this study, we demonstrated the transfer of LM paste composed of Ga-based LM and Ni nanoparticles onto ultrasoft substrates such as biological tissue and gels using sacrificial polyvinyl alcohol (PVA) films. The LM paste pattern fabricated on the PVA film adhered to the ultrasoft substrate along surface irregularities and was transferred without being destroyed by the PVA film before the PVA's dissolution in water. The minimum line width that could be wired was approximately 165 µm. Three-dimensional wiring, such as the helical structure on the gel fiber surface, is also possible. Application of this transfer method to tissues using LM paste wiring allowed the successful stimulation of the vagus nerve in rats. In addition, we succeeded in transferring a temperature measurement system fabricated on a PVA film onto the gel. The connection between the solid-state electrical element and the LM paste was stable and maintained the functionality of the temperature-sensing system. This fundamental study of wiring fabrication and system integration can contribute to the development of advanced electric devices based on ultrasoft substrates.