Most organoids are cultured in Matrigel, a complex and poorly defined matrix that limits our mechanistic understanding. Synthetic hydrogels offer a versatile alternative, providing precise control over mechanical and biochemical cues. Using two topologically different types of hydrogel precursors, branched poly(ethylene glycol) (PEG) and PEG bisdendrons, we have obtained a library of hydrogels via thiol–ene cross-linking with branched PEG-thiol. Their chemical conversion was monitored by Raman spectroscopy, while swelling and mechanical properties, including elastic, viscoelastic, and relaxation parameters, were systematically evaluated. Bisdendron hydrogels dissipate stress through abundant weak interactions, conferring adaptive viscoelastic behavior, an underexplored feature in a 3D culture. To link macromolecular dynamics with bulk properties, polymer chain mobility and internal architecture were probed using MAS solid-state NMR and freeze-fracture cryo-SEM. To introduce bioactivity, RGD peptides were used and immobilized via thiol–ene chemistry, forming spatially organized clusters within the hydrogels. This strategy enables the design of customizable matrices with tunable mechanics, adjustable porosity, and controlled bioactive presentation, closely mimicking native microenvironments. Our platform can provide a chemically defined and versatile toolbox for organoid culturing.
Apartsin et al. (Wed,) studied this question.