Dissertation

Dynamic hydrogels as synthetic extracellular matrices for three- dimensional cell culture

Author: Liu, T.
Date: 26 October 2021
Links: Thesis in Leiden Repository

Synthetic hydrogels that mimic the natural extracellular matrix in the biophysical and biochemical cues it provides to cells are in high demand, however the cell phenotypes as they are observed in vivo in numerous cases have yet to be attained. In this thesis, both chemically-defined supramolecular and covalent hydrogels are prepared that are encoded with bioactive peptides/ proteins, dynamics and porous structural features in order to explore how the modification of polymer materials with various biophysical cues affect cell behavior using various readouts. Through a chemical design, we have shown successful introduction of adhesive peptides that can be identified by cells, through an efficient supramolecular co-assembly approach to prepare biomaterials. We further examine this flexible strategy for coupling of specific peptides to supramolecular monomers to provide matrix interactions for the culture of spheroids based on liver (HepG2) and induced pluripotent stem cells. Also, a dynamic covalent hydrogel system based on thiosulfinate-chemistry to form disulfide bonds was designed and validated to play an important role in supporting the differentiation of induced pluripotent stem cell derived cardiomyocytes. Lastly, gas-forming chemistries that enable control over porosity of the hydrogel materials at the macroscale were examined through the Inverse electron-demand Diels-Alder (IEDDA) reaction with reaction pairs that react with distinct kinetics. Overall, we have engineered dynamic supramolecular and covalent biomaterials using different chemical tools to modulate their biophysical properties that the present to cells, providing guidelines for future biomaterials designs in the field of in vitro 3D cell culture.