Synthetic hydrogel materials can recapitulate the natural cell microenvironment; however, it is equally necessary that the gels maintain cell viability and phenotype while permitting reisolation without stress, especially for use in the stem cell field. Here, we describe a family of synthetically accessible, squaramide-based tripodal supramolecular monomers consisting of a flexible tris(2-aminoethyl)amine (TREN) core that self-assemble into supramolecular polymers and eventually into self-recovering hydrogels. Spectroscopic measurements revealed that monomer aggregation is mainly driven by a combination of hydrogen bonding and hydrophobicity. The self-recovering hydrogels were used to encapsulate NIH 3T3 fibroblasts as well as human-induced pluripotent stem cells (hiPSCs) and their derivatives in 3D. The materials reported here proved cytocompatible for these cell types with maintenance of hiPSCs in their undifferentiated state essential for their subsequent expansion or differentiation into a given cell type and potential for facile release by dilution due to their supramolecular nature.

insulating oxide layer is needed and inevitably leads to a weak coupling. In this regard, by serving as both the sensor channel and the surface, chemically inert graphene with excellent electrical properties, enables ultimate sensitivity towards single or few molecular detections. [13,14] Yet, the target biomolecules binding on receptor biomolecules of several nanometers away from the graphene surface (and ISFET in general), are unable to induce a notable field effect due to electrical screening by counterions in high-salt solutions at direct current or low frequencies, representing a major drawback for biosensing under physiological conditions. To mitigate the fundamental ionic screening effect, high-frequency singlewalled carbon nanotube heterodyne sensors have been used. [15] Nevertheless, the fact that the transconductance-dependent heterodyne output signal could be modeled as a result of an effective double-layer-capacitance coupling between the electrolyte gate and the nanotube channel up to 10 MHz, suggests that ionic screening is still relevant at such high frequencies. [15,16] On the other hand, owing to the high carrier mobility and saturation velocity, [13] graphene FETs (Gr-FETs) have received worldwide interests in the domain of high-frequency electronics, providing an ideal platform for real-time sensing applications under physiological conditions by overcoming the ionic screening of movable ions. [17][18][19] Importantly, in contrast to conventional metal-based interdigitated capacitors or transmission line with invariant electrical properties, the type of carriers as well as the carrier density of Gr-FETs can be effectively tuned using electrolyte gating and/or upon biomolecular adsorption, representing a significant advantage for the development and optimization of advanced high-frequency biosensors.Here, to fully overcome the ionic screening effect in high-salt solutions, we configured electrolyte-gated Gr-FET in reflectometry mode at ultrahigh frequencies (UHF, around 2 GHz) and achieved orders-of-magnitude lower limits of detection (LOD) compared to those of previously reported metal or nanomaterial-based high-frequency sensors. Strikingly, by simultaneously characterized using electrolyte gating and UHF reflectometry, we were able to unmix/differentiate the correlated field-effect and UHF sensing response, thus offering unprecedented capability for real-time monitoring of dielectric-specified biomolecular/cell interactions/activities. These achievements Owing to their excellent electrical properties and chemical stability, graphene field-effect transistors (Gr-FET) are extensively studied for biosensing applications. However, hinging on surface interactions of charged biomolecules, the sensitivity of Gr-FET is hampered by ionic screening under physiological conditions with high salt concentrations up to frequencies as high as MHz.Here, an electrolyte-gated Gr-FET in reflectometry mode at ultrahigh frequencies (UHF, around 2 GHz), where the ionic screening is fully cancelled and the dielectri...

A major challenge in the use of HepG2 cell culture models for drug toxicity screening is their lack of maturity in 2D culture. 3D culture in Matrigel promotes the formation of spheroids that express liver‐relevant markers, yet they still lack various primary hepatocyte functions. Therefore, alternative matrices where chemical composition and materials properties are controlled to steer maturation of HepG2 spheroids remain desired. Herein, a modular approach is taken based on a fully synthetic and minimalistic supramolecular matrix based on squaramide synthons outfitted with a cell‐adhesive peptide, RGD for 3D HepG2 spheroid culture. Co‐assemblies of RGD‐functionalized squaramide‐based and native monomers resulted in soft and self‐recovering supramolecular hydrogels with a tunable RGD concentration. HepG2 spheroids are self‐assembled and grown (≈150 µm) within the supramolecular hydrogels with high cell viability and differentiation over 21 days of culture. Importantly, significantly higher mRNA and protein expression levels of phase I and II metabolic enzymes, drug transporters, and liver markers are found for the squaramide hydrogels in comparison to Matrigel. Overall, the fully synthetic squaramide hydrogels are proven to be synthetically accessible and effective for HepG2 differentiation showcasing the potential of this supramolecular matrix to rival and replace naturally‐derived materials classically used in high‐throughput toxicity screening.

Graphene Biosensors In article 2106666, Xiaoyan Zhang, Grégory F. Schneider, Wangyang Fu, and co‐workers demonstrate graphene biosensors operating at ultrahigh frequencies, where the conductivity of high‐salt solutions and thus the ionic screening is fully cancelled. Dielectric‐modulated detection of the binding of streptavidin molecules to biotin molecules that are noncovalently anchored on the graphene surface is demonstrated using the developed graphene biosensors.

We report the synthesis and self-assembly of a library of squaramide-based bolaamphiphiles with variable hydrophobic and hydrophilic domain sizes to understand their effect on the formation of supramolecular polymer nanoparticles.