(695b) Invited: Thiol-Ene Click Hydrogels for Cytocompatible Generation and Rapid Recovery of Insulin-Secreting Cell Spheroids

Poly(ethylene glycol) or PEG-based hydrogels have been widely used for cell delivery and as a platform for 3D cell culture.  Recently, PEG hydrogels formed by step-growth thiol-ene photopolymerizations have emerged as attractive and versatile matrices for tissue regeneration.  Compared to chain-growth PEG diacrylate (PEGDA) hydrogels, gels prepared from thiol-ene click reactions have homogeneous network structures, higher monomer conversion, and enhanced mechanical properties.  Thiol-ene click reactions also preserve all of the preferential properties offered by photopolymerizations, specifically rapid and spatial-temporal controlled over gelation kinetics.  In addition, thiol-ene PEG hydrogels can be rendered biodegradable by using enzyme sensitive peptide sequences as crosslinkers.  Here, we compare properties of chain-growth and step-growth photopolymerizations in the context of pancreatic beta cell encapsulation.  In addition to the above-mentioned benefits, we found that step-growth thiol-ene click reactions are highly cytocompatible for pancreatic beta cells, even when cells were encapsulated at very low density.   Beta cells (MIN6) not only had high viability in thiol-ene click hydrogels, they also proliferated to form narrowly dispersed cell spheroids.  Furthermore, when a chymotrypsin sensitive peptide sequence was used as gel crosslinker, insulin-secreting cell spheroids can be rapidly and safely recovered (within 5min) from the thiol-ene hydrogels via a surface erosion mechanism. These studies demonstrate the advantages and versatility of thiol-ene photopolymeirzations in tissue engineering and regenerative medicine applications.