Synthetic cell culture matrices are essential for developing accurate in vitro models because they allow researchers to precisely control the biochemical and biophysical properties of the cell microenvironment. Unlike natural matrices, which can vary significantly in composition and mechanical properties, synthetic matrices offer reproducibility and customizability—enabling the study of specific cell-matrix interactions under defined conditions. This control is crucial for mimicking the complexity of native tissues, supporting cell behaviors such as adhesion, migration, and differentiation in a way that closely resembles in vivo environments. Additionally, synthetic matrices can be engineered to incorporate specific cues, such as growth factors or mechanical stiffness, to model disease states or test drug responses more reliably. By providing a consistent and tunable platform, synthetic matrices help bridge the gap between simplified 2D cultures and the complexity of living organisms, ultimately improving the relevance and predictive power of in vitro studies for drug screening and toxicity testing.
Supramolecular materials provide a powerful synthetic platform to emulate the structure and function of biopolymers of the extracellular matrix. However, one of the main challenges in using supramolecular materials to mimic the extracellular matrix lies in their inherent mechanical properties. Supramolecular materials are assembled through reversible, non-covalent interactions—such as hydrogen bonding or host-guest chemistry—which provide dynamic and adaptable environments ideal for soft, embryonic-like tissues. However, these weak interactions typically result in materials that are too soft and lack the toughness required to replicate the rigid mechanical cues found in mature or fibrotic tissues, such as bone, cartilage, or scarred heart muscle. While these materials excel at recapitulating the softness and responsiveness of early developmental stages, their inability to achieve high stiffness and durability without compromising biocompatibility or cellular interaction limits their use in modeling or repairing stiffer biological environments.
The objectives of this ERC project are to create biocompatible hybrid supramolecular hydrogels that can transition from soft to stiff, mimicking the evolving mechanical properties of natural tissues in a controlled manner. These materials will be used to direct the behaviour of stem cells and cardiomyocytes derived from them in 3D in vitro culture. We will apply the developed materials for 3D stem cell expansion and in cardiac organ-on-chip technologies exploring their potential to replace and outperform animal-derived matrices commonly used in the field.
