A biocompatible hydrogel with improved stiffness and hydrophilicity for modular tissue engineering assembly

Surface tension driven assembly is a simple and rapid strategy in "modular" tissue engineering to fabricate three-dimensional (3D) structures with predefined geometrical and biological features. Besides the biocompatibility for encapsulated cells, the mechanical and hydrophilic properties of the microgel are the utmost two factors for assembly and structure preservation. Herein, we developed a new composite hydrogel based on photocrosslinkable methacrylated gelatin (GelMA) and methacrylated alginate (AlgMA) for modular tissue engineering assembly. Based on the high cellular bioactivity of GelMA, inflexible AlgMA with a large number of hydrophilic groups was introduced to optimize the hydrogel assembly performance. The results revealed that the mechanical stiffness, swelling ratio and hydrophilicity were improved greatly, and the nutrient permeability as well as the cellular activity remained at a relatively high level simultaneously. The enhanced stiffness and hydrophilicity were helpful for the surface tension driven assembly, and the high nutrient permeability was conducive to the activity of encapsulated cells. Moreover, microgels with different shapes were fabricated, and microengineered complex structures constructed with spatial organized cell distribution and specific functions, such as osteon-like structure containing both osteogenic and vascularized area, were successfully generated by "Lock and key" and "Concentric double-ring" assemblies. The composite hydrogel provides a potential candidate material for modular tissue engineering.