Compositions and methods are provided for the manufacture and use of hydrogels with increased permeability to macromolecules with minimum loss of matrix mechanical strength and prepolymer viscosity for patternability. The hydrogels of the invention are formed from a prepolymer, which is polymerized in the presence of hydrophobic nanoparticles. In some embodiments of the invention cells are present during polymerization, and are encapsulated by the hydrogel. A high interfacial energy between the hydrophobic substrate and the aqueous polymerizing solution disrupts the hydrogel network structure, leading to network defects that increase permeability without loss of patternability.