A spatial patternable macroporous hydrogel with cell-affinity domains to enhance cell spreading and differentiation

Cell adhesion and spreading are two essential factors for anchorage-dependent cells such as osteocytes. An adhesive macroporous hydrogel system, in which cell-affinitive domains and sufficient cytoskeleton reorganization space were simultaneously constructed, was proposed in this report to support cell adhesion and spreading, respectively, and facilitate cell differentiation and function establishment eventually. The adhesive macroporous alginate hydrogel was developed by RGD peptide graft and gelatin microspheres hybridization to generate cellular adhesion sites and highly interconnected macropores. The successful stretched morphology and enhanced osteogenic differentiation of MG-63 cells in this modified alginate hydrogel showed clearly the feasibility that cell function may be effectively facilitated. Besides, this hydrogel model can be further applied to construct complex micropatterned structure, such as individual microgels in shapes of circle, square, cross and ring, and osteon-like structure containing both osteogenic and vascularized area generated by a double-ring assembly. These results should provide this adhesive macroporous photocrosslinkable hydrogel system as potential three-dimensional scaffolds for guiding tissue formation, especially for the bioengineering of tissues that have multiple cell types and require precisely defined cell–cell and cell–substrate interactions.