Madhumita Patel

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

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 versus Mesocomposite for Osteogenic Differentiation of Tonsil‐Derived Mesenchymal Stem Cells

Injectable inorganic/organic composite systems consisting of well-defined mesocrystals (4-8 μm) of calcium phosphate and polypeptide thermogel significantly enhance the osteogenic differentiation of the tonsil derived mesenchymal stem cells (TMSCs). Compared to composite systems incorporating nanoparticles (10-100 nm) or pure hydrogel systems, osteogenic biomarkers including alkaline phosphatase (ALP), bone morphogenetic protein 2, and osteocalcin are highly expressed at both the mRNA level and the protein level in the mesocrystal composite systems. ALP activity of differentiated cells is also significantly higher in the mesocomposite systems compared to the nanocomposite systems or the pure hydrogel systems. The mesocomposite systems provide not only hard surfaces for binding the cells/proteins by the inorganic mesocrystals but also a soft matrix for holding the cells by the hydrogel. Through the current research, (1) a novel method of preparing mesocrystals is developed, (2) TMSCs are proved as a new resource of stem cells, and (3) the mesocomposite systems are proved to be a promising tool in controlling stem cell differentiation. (4) Finally, the research emphasizes the significance of mesoscience as a new perspective of science in controlling cell and material interfaces.

Microsphere-Incorporated Hybrid Thermogel for Neuronal Differentiation of Tonsil Derived Mesenchymal Stem Cells

Neuronal differentiation of tonsil-derived mesenchymal stem cells (TMSCs) is investigated in a 3D hybrid system. The hybrid system is prepared by increasing the temperature of poly(ethylene glycol)-poly(l-alanine) aqueous solution to 37 °C through the heat-induced sol-to-gel transition, in which TMSCs and growth factor releasing microspheres are suspended. The in situ formed gel exhibits a modulus of 800 Pa at 37 °C, similar to that of brain tissue, and it is robust enough to hold the microspheres and cells during the 3D culture of TMSCs. The neuronal growth factors are released over 12-18 d, and the TMSCs in a spherical shape initially undergo multipolar elongation during the 3D culture. Significantly higher expressions of the neuronal biomarkers such as nuclear receptor related protein (Nurr-1), neuron specific enolase, microtubule associated protein-2, neurofilament-M, and glial fibrillary acidic protein are observed in both mRNA level and protein level in the hybrid systems than in the control experiments. This study proves the significance of a controlled drug delivery concept in tissue engineering or regenerative medicine, and a 3D hybrid system with controlled release of growth factors from microspheres in a thermogel can be a very promising tool.

Phosphorylcholine-Based Zwitterionic Biocompatible Thermogel

Zwitterionic polymers have been investigated as surface-coating materials due to their low protein adsorption properties, which reduce immunogenicity, biofouling, and bacterial adsorption of coated materials. Most zwitterionic polymers, reported so far, are based on (meth)acrylate polymers which can induce toxicity by residual monomers or amines produced by degradation. Here, we report a new zwitterionic polymer consisting of phosphorylcholine (PC) and biocompatible poly(propylene glycol) (PPG) as a new thermogelling material. The PC-PPG-PC polymer aqueous solution undergoes unique multiple sol-gel transitions as the temperature increases. A heat-induced unimer-to-micelle transition, changes in ionic interactions, and dehydration of PPG are involved in the sol-gel transitions. Based on the broad gel window and low protein adsorption properties, the PC-PPG-PC thermogel is proved for sustained delivery of protein drugs and stem cells over 1 week.

Transition-metal-based layered double hydroxides tailored for energy conversion and storage

Currently, energy storage devices draw considerable attention owing to the growing need for clean energy. The depletion of fossil fuels and the generation of greenhouse gases have led to the development of alternative, environmentally friendly energy storage devices. Supercapacitors with high power densities are excellent devices for energy storage. Although carbon-based materials are widely used in such devices, their non-faradic behavior in electrical double layer capacitors (EDLCs) limits the maximum power density that can be generated. In contrast, the faradaic mechanism of transition metal hydroxides results in better capacitance rates along with good stability during cycling. This review is confined to nickel cobalt layered double hydroxides (NiCo LDHs) classified based on the fabrication of electrodes for application in supercapacitors. We discuss the growth of the active LDH material in situ or ex situ on the current collector and how the synthesis can affect the crystal structure as well as the electrochemical performance of the electrode.

Injectable thermogel for 3D culture of stem cells

Thermogel is an aqueous polymer solution that undergoes sol-to-gel transition as the temperature increases. Cells, growth factors, and signaling molecules can be incorporated simultaneously during the sol-to-gel transition. The cytocompatible procedure makes the thermogel an excellent platform for 3D culture of stem cells. This review focuses on the crucial questions that need to be addressed to achieve effective differentiation of stem cells into target cells, comprising low modulus, cell adhesion, and controlled supply of the growth factors. Recent progress in the use of thermogel as a 3D culture system of stem cells is summarized, and our perspectives on designing a new thermogel for 3D culture and its eventual application to injectable tissue engineering of stem cells are presented.

Chiro-Optical Modulation for NURR1 Production from Stem Cells

Nuclear receptor related 1 (NURR1) is an essential protein for maintenance of dopaminergic neurons in adult midbrain of which deficiency leads to Parkinsons disease. To enhance the NURR1 production of neural cells, various approaches are under investigation. Here we report that NURR1 is highly expressed in stem cells by exposure to an L-polarized blue light emitting diode (LED). Compared to stem cells cultured in the absence of a LED, under polarized green and red LEDs, the stem cells exposed to a polarized blue LED significantly enhanced neuronal biomarkers such as neurofilament M (NFM) and neuron specific enolase (NSE) at both mRNA and protein levels. In particular, NURR1 was selectively enhanced by the stem cells exposed to the L-polarized blue LED. Stem cells exposed to the L-polarized blue LED increased mitochondrial ATP and intracellular calcium ions, which support neuronal differentiation of the stem cells. This study suggests that chiro-optical treatments by using polarized light with a specific wavelength can be used for engineering of stem cells with enhanced specific biochemicals, which may open a new method for a specific disease.

Polypeptide Thermogels as Three-Dimensional Scaffolds for Cells

Background:Thermogel is an aqueous solution that exhibits a sol-to-gel transition as the temperature increases. Stem cells, growth factors, and differentiating factors can be incorporated in situ in the matrix during the sol-to-gel transition, leading to the formation of a three-dimensional (3D) cell-culture scaffold.Methods:The uses of thermogelling polypeptides, such as collagen, Matrigel™, elastin-like polypeptides, and synthetic polypeptides, as 3D scaffolds of cells, are summarized in this paper.Results:The timely supply of growth factors to the cells, cell survival, and metabolite removal is to be insured in the cell culture matrix. Various growth factors were incorporated in the matrix during the sol-to-gel transition of the thermogelling polypeptide aqueous solutions, and preferential differentiation of the incorporated stem cells into specific target cells were investigated. In addition, modulus of the matrix was controlled by post-crosslinking reactions of thermogels or employing composite systems. Chemical functional groups as well as biological factors were selected appropriately for targeted differentiation of the incorporated stem cells.Conclusion:In addition to all the advantages of thermogels including mild conditions for cell-incorporation and controlled supplies of the growth factors, polypeptide thermogels provide neutral pH environments to the cells during the degradation of the gel. Polypeptide thermogels as an injectable scaffold can be a promising system for their eventual in vivo applications in stem cell therapy.