In situ Forming Annealed Protein Microgels: A New Generation of ECM-Mimetic Microporous Hydrogels

Bulk hydrogels with nanoporous structures have widely been used in tissue engineering and regenerative medicine. These gels are typically made up of randomly crosslinked hydrophilic polymer networks, which have coupled stiffness and porosity. In a simplified model, the stiffer the gel the smaller the pores. Such characteristic limits the applications of bulk hydrogels in 3D cellular engineering wherein stiff scaffolds with large pores are required. In this presentation, we will discuss some of our recent advances in microengineering chemically modified protein microgels based on their orthogonal thermo-chemical responsivity to fabricate biomimetic microporous hydrogels with decoupled stiffness and porosity. We show how these hydrogels support 3D cell viability and proliferation while their bulk counterparts result in cell death. We further demonstrate how the properties of individual microgels regulate the behavior of annealed, macro-scale hydrogel constructs. This technology may be generalized for other thermo-responsive polymers, opening a new horizon for converting bulk hydrogels to beaded hydrogels with decoupled porosity and stiffness for a broad range of applications in healthcare, food, water, and energy.