Modularly assembled porous cell-laden hydrogels

Porous cell-laden hydrogels have been modularly assembled to address the challenges in 3-dimensional tissue engineering. Microgels photolithographically fabricated from solutions of poly(ethylene glycol) diacrylate are assembled into large porous constructs in the presence of a polypeptide-based, physically bonded cross-linker. The assembly occurs through a physiologically permissive Michael-type addition reaction between the acrylate groups on the surface of the microgels and the thiol groups on the cross-linker. The constructs assembled from star-shaped microgels exhibit higher porosity, permeability, and pore interconnectivity than those formed from circle- and square-shaped microgels. The correlation between the properties of assembled constructs and the morphological features of microgels suggests the possibility for bottom-up modulation of the construct properties. The high pore interconnectivity revealed on the level of individual microgels suggests that these constructs are suitable for tissue engineering. Cells remain viable inside centimeter-sized constructs when cultured under perfusion. These constructs have the combined advantages of preformed porous scaffolds and in situ forming hydrogels in allowing enhanced mass transfer, uniform cell seeding, and protection of cells from excessive, non-physiological shear stress. Large constructs can be assembled in one step and have no limitations in size. This method will provide opportunities to create large 3-dimensional tissue engineered products.