Dipeptide Self-Assembled Hydrogels with Tunable Mechanical Properties and Degradability for 3D Bioprinting

Supramolecular hydrogels self-assembled from short peptides have shown great potential as biomimetic extracellular matrices with controllable properties designed at the molecular level. However, their weak mechanical strength still remains a big challenge for 3D bioprinting. Herein, two oppositely charged dipeptides are designed and used as bioinks in a "layer-by-layer" alternative bioprinting strategy. During printing, in situ gelation is achieved by electrostatic interactions between two dipeptides without additional cross-linking procedures. The binary hydrogels have tunable mechanical properties with elastic moduli ranging from 4 to 62 kPa and controllable biodegradability from days to weeks, which can ideally mimic the natural environment of a variety of cell types. It is demonstrated that the hydrogel scaffold enables the formation, growth, and natural release of HepaRG spheroids with sizes up to millimeters. This strategy may be suitable to develop a series of new bioink materials based on peptides and other supramolecular polymers for 3D bioprinting.