Dual Ionic and Photo-Crosslinked Alginate Hydrogels for Micropatterned Spatial Control of Material Properties and Cell Behavior

Biomaterial properties such as mechanics, degradation rate, and cell adhesivity affect cell behaviors including spreading, proliferation, and differentiation. To engineer complex tissues, it is often desirable to achieve precise spatial control over these properties. Here, methacrylated alginate (MA-ALG) was used to create hydrogels comprising a single base material with regions of different types and levels of crosslinking and subsequently different material properties. Ionic and ultraviolet light crosslinking mechanisms were combined to create dual-crosslinked hydrogels with significantly increased stiffness and decreased swelling compared to calcium-crosslinked or UV-crosslinked hydrogels. MC3T3 cells showed significantly enhanced proliferation on the surface of dual-crosslinked hydrogels compared with calcium-crosslinked hydrogels. Photomasks were then used to create patterned hydrogels with precise spatial control over regions that were only calcium-crosslinked versus dual-crosslinked. This spatial variation in crosslinking mechanism permitted local regulation of the hydrogel physical properties and alignment of cells seeded on their surface. Photomasks were also used to create hydrogels with patterned presentation of cell adhesion ligands, leading to spatial control over cell attachment and proliferation. This biomaterial system can be useful for providing patterned, instructive cues to guide cell behavior for engineering complex tissues.