Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

Therapeutic proteins, such as growth factors (GFs), have been used in tissue engineering (TE) approaches for their ability to provide signals to cells and orchestrate the formation of functional tissue. However, to be effective and minimize off-target effects, GFs should be delivered at the target site with temporal control. In addition, protein drugs are typically sensitive water soluble macromolecules with delicate structure. As such, hydrogels, containing large amounts of water, provide a compatible environment for the direct incorporation of proteins within the hydrogel network, while their release rate can be tuned by engineering the network chemistry and density. Being formed by transient crosslinks, afforded by non-covalent interactions, supramolecular hydrogels offer important advantages for protein delivery applications. This review describes various types of supramolecular hydrogels using a repertoire of diverse building blocks, their use for protein delivery and their further application in TE contexts. By reviewing the recent literature on this topic, the merits of supramolecular hydrogels are highlighted as well as their limitations, with high expectations for new advances they will provide for TE in the near future.