Academic Awards 2024 booklet

81 Design rules to control supramolecular hydrogel-cell interactions Biomaterials are increasingly being used to grow cells into functional tissues, for applications like drug screening or as tissue replacements. When utilizing biomaterials to grow cells, it is crucial to accurately mimic the mechanical, bioactive, and dynamic properties of the environment surrounding cells; the extracellular matrix (ECM). In endeavors to replicate the ECM using biomaterials, different approaches have emerged to capture its essential characteristics. However, current options lack orthogonal control over biomaterial properties across different length scales. Therefore, we developed ECM mimics that do allow for orthogonal control over properties at the nano-, micro- and macroscale, to extract guidelines for each matrix property underlying the cell-material interaction. To meet this aim, supramolecular hydrogels were designed and formulated, which are formed through non-covalent interactions between their monomers, rendering them highly modular and dynamic, while also able to isolate the influence of only one matrix property on cellular behavior. Different cell types and organoids were grown in the supramolecular hydrogels. Based on the most important findings, guidelines are proposed to control cell-material interactions for each matrix property. Future work may utilize these guidelines that control the cell-material interface to advance many fields, ranging from regenerative medicine to bio-electronics. Figure 1: Cover PhD Dissertation Laura Rijns. In grey a cell, spreading and holding on to supramolecular polymeric hydrogels (light blue), which act as mimic of the ECM. This cell-material interaction relies on the binding of the cell to ECM ligands (dark blue). Figure 2: Overview and aim of my PhD thesis, in which we utilize supramolecular hydrogels as mimics of the ECM to grow cells and organoids. The supramolecular hydrogels have orthogonally controllable mechanical, bioactive and dynamic properties, enabling to study the influence of only one matrix property on cellular behavior. Design rules are proposed that control the cell-material interaction for each matrix property. The proposed design rules can be used to not only advance the regenerative medicine field but also for bio-electronic applications.