Design and Synthesis of Hydrolytically Degradable PEG Carbamate, Carbonate, and Ester Derivatives to Induce Reversible Biostasis.

Control over network chemistry and connectivity of hydrogels is critical for the generation of tunable material properties, including material degradation for applications such as tissue scaffolding and drug delivery. Here, the degradation of hydrogels employing different hydrolytically cleavable groups including benzamide and syringic acid-derived carbamates, kojic acid-derived carbonates, and kojic acid-derived esters under physiological conditions was studied. Tunability of the hydrogel network degradation was demonstrated by varying the hydrolytically degradable moiety, macromer functionality, and copolymerization with hydrolytically stable macromers. These hydrolytically labile macromers were introduced and cross-linked intracellularly to induce transient cellular quiescence in MCF10A cells, resulting in a highly tunable degradation mechanism that is shown to be capable of inducing reversible biostasis of cells with 60% of cells treated with the carbonate macromer returning to their proliferative state and rebounding in translational activity after 72 h, while the biological activity of the carbamate macromer-treated cells remained suppressed.