Biomaterials for tissue engineering are commonly constructed from degradable 3D porous matrices which provide support and guidance for cellular colonization and ingrowth. In a reactor in order to regenerate large sections of tissue required for bladder, skin, or blood vessel regeneration the cell seeded construct must be matured in a bioreactor. The flow distribution within the bioreactor affects cellular colonization and extracellular matrix (ECM) production by controlling the distribution of nutrients as well as the shear stress profiles within the reactor. Changes to the porous structure alter both the pressure required for perfusion through the material and the shear forces present within the structure. Therefore, this study focused how changing the features of the material's 3D porous architecture affected both the pressure drop across the structure and the shear stresses within the structure. The flow distribution, pressure drop, and shear stresses within a thin rectangular reactor (2.5 cm × 8 cm × 0.2cm) were evaluated using computational simulations and bioreactor experiments. The simulations were performed using commercially available software, CFX 11 (ANSYS Inc, Canonsburg, PA.) and/or Comsol 3.3 Multiphysics (COMSOL, Inc., Burlington, MA). In order to account for both viscous and drag forces, flow through the porous structure was modeled using the Brinkman Equation, which characterizes the porous structure using pore size and the number of pores per unit area. The effect of matrix construction was modeled by changing both pore size and pores per area, the number of pores per area increases as the pore size shrinks, and the effect of cellular ingrowth and ECM production was modeled by keeping the pores per area constant while shrinking the pore size. A variety of values were tested ranging from 200 µm pores, 15 pores/mm^2 to 10 µm pores, 1500 pores/mm^2. The values centered on the experimentally measured value of 85 µm pores, 120 pores/mm^2 (determined from chitosan scaffolds freeze dried at -80ºC). Both computational and experimental results showed expected flow profiles with increased pressure drop and shear stress as pore size decreased. This modeling strategy allows better understanding of the effect of 3D porous architecture on bioreactor properties, and shows promise in enhancing the design of tissue engineering materials.