Cell Microencapsulation Within Engineered Hyaluronan Elastin‐Like Protein (HELP) Hydrogels

Abstract Three‐dimensional cell encapsulation has rendered itself a staple in the tissue engineering field. Using recombinantly engineered, biopolymer‐based hydrogels to encapsulate cells is especially promising due to the enhanced control and tunability it affords. Here, we describe in detail the synthesis of our hyaluronan (i.e., hyaluronic acid) and elastin‐like protein (HELP) hydrogel system. In addition to validating the efficacy of our synthetic process, we also demonstrate the modularity of the HELP system. Finally, we show that cells can be encapsulated within HELP gels over a range of stiffnesses, exhibit strong viability, and respond to stiffness cues. © 2023 Wiley Periodicals LLC. Basic Protocol 1 : Elastin‐like protein modification with hydrazine Basic Protocol 2 : Nuclear magnetic resonance quantification of elastin‐like protein modification with hydrazine Basic Protocol 3 : Hyaluronic acid–benzaldehyde synthesis Basic Protocol 4 : Nuclear magnetic resonance quantification of hyaluronic acid–benzaldehyde Basic Protocol 5 : 3D cell encapsulation in hyaluronan elastin‐like protein gels