Cell to matrix interactions affect in vitro cell adherence and proliferation and further decide the fate of tissue development for biomedical applications. This study demonstrates the role of crosslinking in altering the surface properties of 3D porous cryogel matrices. Glutaraldehyde and 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide crosslinkers are used separately for the crosslinking of alginate and gelatin (i.e., AG_G and AG_EN), respectively. The difference in crosslinking affects the physiochemical properties of these matrices leading to variable cell behavior as demonstrated using four different cell types, which show homogeneous cell growth in AG_G and spheroid cell growth in AG_EN. The present study shows successful use of controlled crosslinking in directing the cell growth for tissue engineering.