Abstract
The extracellular matrix (ECM) forms through hierarchical assembly of small and larger polymeric molecules into a transient, hydrogel-like fibrous network that provides mechanical support and biochemical cues to cells. Synthetic, fibrous supramolecular networks formed via non-covalent assembly of various molecules are therefore potential candidates as synthetic mimics of the natural ECM, provided that functionalization with biochemical cues is effective. Here, combinations of slow and fast exchanging molecules that self-assemble into supramolecular fibers are employed to form transient hydrogel networks with tunable dynamic behavior. Obtained results prove that modulating the ratio between these molecules dictates the extent of dynamic behavior of the hydrogels at both the molecular and the network level, which is proposed to enable effective incorporation of cell-adhesive functionalities in these materials. Excitingly, the dynamic nature of the supramolecular components in this system can be conveniently employed to formulate multicomponent supramolecular hydrogels for easy culturing and encapsulation of single cells, spheroids, and organoids. Importantly, these findings highlight the significance of molecular design and exchange dynamics for the application of supramolecular hydrogels as synthetic ECM mimics.
Highlights
Dynamic hydrogels based on non-covalent or dynamic covalent is proposed to enable effective incorporation of cell-adhesive functionalities in chemistry are increasingly preferred as these materials
Supramolecular hydrogels based on combinations of slow and fast exchanging molecules have shown to function as synthetic extracellular matrix (ECM) mimics for diverse cell culture schemes, ranging from single cells to spheroids, and organoids
This work demonstrates the importance of molecular exchange dynamics on effective functionalization of supra molecular hydrogels with adhesive ligands
Summary
Two types of supramolecular building blocks were designed for the formulation of our supramolecular hydrogels (Figure 1a). YAP is widely known as a transcriptional regulator that acts as a universal mechanotransducer, mediating the cellular response to the mechanical cues of the ECM.[43,44] the YAP nuclear-cytoplasmic translocation has been correlated with cellular changes in response to materials with different stiffness, degradability, or stress relaxation.[26,43,45] Our results indicated that altering the M/B ratio (B1.5M3.5 vs B0.5.M4.5) and UPy-cRGD concentration (1 mm vs 3 mm) among the cell-adhesive compositions did not affect the YAP translocation in cells cultured onto these hydrogels (Figure S12, Supporting Information). A budding-like morphology[53] emerged at the organoid periphery when UPy-cRGD additives were included in the hydrogel composition, indicating the ability of our supramolecular hydrogels to serve as a modular platform for facilitating organoid culture
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