The Influence of Matrix Degradation and Functionality on Cell Survival and Morphogenesis in PEG-Based Hydrogels

Two norbornene-functionalized PEG macromers are synthesized to render hydrogels with different hydrolytic degradability. Dithiol-containing linkers such as dithiothreitol or biscysteine-containing peptides are used to control proteolytic degradability. The influence of thiol-ene gel degradability on cell survival and morphogenesis in 3D is assessed using hMSCs and pancreatic MIN6 cells. The initial cell viability can be negatively affected in highly crosslinked thiol-ene hydrogels. When cells are encapsulated in thiol-ene gels lacking cell-adhesive motifs, their survival and proliferation are promoted in more hydrolytically labile hydrogels. The degree of 3D cell spreading in encapsulated hMSCs is enhanced when the matrices are immobilized with cell-adhesive motifs.