Modular multifunctional poly(ethylene glycol) hydrogels for stem cell differentiation

Synthetic polymers are employed to create highly defined microenvironments with controlled biochemical and biophysical properties for cell culture and tissue engineering. Chemical modification is required to input biological or chemical ligands, which often changes the fundamental structural properties of the material. Here, a simple modular biomaterial design strategy is reported that employs functional cyclodextrin nanobeads threaded onto poly(ethylene glycol) (PEG) polymer necklaces to form multifunctional hydrogels. Nanobeads with desired chemical or biological functionalities can be simply threaded onto the PEG chains to form hydrogels, creating an accessible platform for users. The design and synthesis of these multifunctional hydrogels are described, structure-property relationships are elucidated, and applications ranging from stem cell culture and differentiation to tissue engineering are demonstrated. Poly(ethylene glycol) is used to create synthetic hydrogel microenvironments for cells, but the ether backbone lacks sites for functionalization. Here, supramolecular chemistry is applied to create modular hydrogels using α-cyclodextrins modified with biological and chemical functional groups with independently controlled crosslinking densities designed to direct stem cell functions.