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.

Supramolecular materials provide unique opportunities to mimic both the structure and mechanics of the biopolymer networks that compose the extracellular matrix. However, strategies to modify their filamentous structures in space and time in 3D cell culture to study cell behavior as encountered in development and disease are lacking. We herein disclose a multicomponent squaramide-based supramolecular material whose mechanics and bioactivity can be controlled by light through co-assembly of a 1,2-dithiolane (DT) monomer that forms disulfide cross-links. Remarkably, increases in storage modulus from ∼200 Pa to >10 kPa after stepwise photo-cross-linking can be realized without an initiator while retaining colorlessness and clarity. Moreover, viscoelasticity and plasticity of the supramolecular networks decrease upon photo-irradiation, reducing cellular protrusion formation and motility when performed at the onset of cell culture. When applied during 3D cell culture, force-mediated manipulation is impeded and cells move primarily along earlier formed channels in the materials. Additionally, we show photopatterning of peptide cues in 3D using either a photomask or direct laser writing. We demonstrate that these squaramide-based filamentous materials can be applied to the development of synthetic and biomimetic 3D in vitro cell and disease models, where their secondary cross-linking enables mechanical heterogeneity and shaping at multiple length scales.

A novel protocol for the synthesis of perylene diimides (PDIs), by reacting perylene dianhydride (PDA) with aliphatic amines is reported. Full conversions were obtained at temperatures between 20 and 60˚C,...

We present a sustainable, inherently safe battery chemistry that is based on widely available and cheap materials, that is, iron and manganese hosted in alginate bio-material known from the food and medical industry. The resulting battery can be recycled to allow circularity. The electrodes were synthesised by the alginate caging the multi-valent metals to form a hydrogel in an aqueous environment. Characterisation includes FTIR, XPS and Mössbauer spectroscopy. The electrochemical performance of the electrodes was investigated by performing cyclic voltammetry (CV) and (dis)charge experiments. Mn and Fe ions show good co-ordination with the alginic acid with higher oxidation states demonstrating complex bonding behaviour. The non-optimised iron and manganese alginate electrodes already exhibit a cycling efficiency of 98% and 69%, respectively. This work shows that Fe and Mn atomically disperse in a bio-based host material and can act as electrodes in an aqueous battery chemistry. While demonstrated at cell level, it is furthermore explained how these materials can form the basis for a (semi-solid) flow cell.