Composite System of Graphene Oxide and Polypeptide Thermogel As an Injectable 3D Scaffold for Adipogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells

Abstract

As two-dimensional (2D) nanomaterials, graphene (G) and graphene oxide (GO) have evolved into new platforms for biomedical research as biosensors, imaging agents, and drug delivery carriers. In particular, the unique surface properties of GO can be an important tool in modulating cellular behavior and various biological sequences. Here, we report that a composite system of graphene oxide/polypeptide thermogel (GO/P), prepared by temperature-sensitive sol-to-gel transition of a GO-suspended poly(ethylene glycol)-poly(L-alanine) (PEG-PA) aqueous solution significantly enhances the expression of adipogenic biomarkers, including PPAR-γ, CEBP-α, LPL, AP2, ELOVL3, and HSL, compared to both a pure hydrogel system and a composite system of G/P, graphene-incorporated hydrogel. We prove that insulin, an adipogenic differentiation factor, preferentially adhered to GO, is supplied to the incorporated stem cells in a sustained manner over the three-dimensional (3D) cell culture period. On the other hand, insulin is partially denatured in the presence of G and interferes with the adipogenic differentiation of the stem cells. The study suggests that a 2D/3D composite system is a promising platform as a 3D cell culture matrix, where the surface properties of 2D materials in modulating the fates of the stem cells are effectively transcribed in a 3D culture system.

Nanocomposite smart hydrogels with improved responsiveness and mechanical properties: A mini review

“…[47][48][49] Contrarily, the weak forces such as hydrogen bonding and hydrophobic interactions are generated to support the stable hydrogel networks. 50,51 For examples, Yang et al reported a novel nanocomposite poly (2-acrylamido-2-methylpropanesulfonic acid)-based hydrogel with improved electro-responsiveness and mechanical properties by introducing reduced graphene oxide (rGO) sheets into poly(2-acrylamido-2-methylpropanesulfonic acid-coacrylamide) (poly[AMPS-co-AAm]) hydrogel network. 46 The prepolymerized solution containing AMPS, AAm, BIS, graphene oxide (GO) sheets, hydrazine hydrate, and ammonia solution is firstly treated by an ultrasound for 10 min to disperse GO sheets homogeneously in the solution [ Fig.…”

Multivalent Interactions between 2D Nanomaterials and Biointerfaces

“…Adipose tissue is another key component necessary for soft tissue reconstruction. Several studies have explored the effects of graphene‐based materials on adipogenic differentiation of stem cells . GO does not interfere with adipogenesis due to electrostatic binding with insulin, but pristine graphene greatly suppresses this process .…”

“…Several studies have explored the effects of graphene‐based materials on adipogenic differentiation of stem cells . GO does not interfere with adipogenesis due to electrostatic binding with insulin, but pristine graphene greatly suppresses this process . In situ‐formed, GO‐incorporated hydrogels have shown excellent results as a 3D matrix for enhancing adipogenic differentiation of the incorporated stem cells …”

Nanocomposite Hydrogels and Their Applications in Tissue Engineering

“…The prepared NC hydrogel showed enhanced chondrogenic differentiation biomarker expression and chondrogenic differentiation of stem cells in the 2D/3D hybrid systems. Later, the same group reported the use of thermoresponsive PEG‐ L –PA/GO for the adipogenic differentiation of TMSCs . The PEG‐ L –PA/GO showed enhanced expression of adipogenic biomarkers, resulting in excellent adipogenic differentiation in comparison to both the graphene‐incorporated hydrogel and the hydrogel itself due to better adhesion of the adipogenic differentiation factor (insulin) on the large surface area provided by GO.…”