Effect of scaffold architecture on diffusion of oxygen in tissue engineering constructs
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Viable tissue formation is often observed in peripheral regions of tissue engineering scaffolds whereas the interior fails to support viable tissue. This could be attributed to the fact that as cells within the pores of the scaffold begin to proliferate and secrete extracellular matrix, they simultaneously begin to occlude the pores and decrease supply of nutrients to the interior. Since transport within the scaffold is mainly a function of diffusion, careful design of the diffusion characteristics of the scaffold is critical. These transport issues relate to oxygen and nutrient delivery, waste removal, protein transport and cell migration, which in turn are governed by scaffold porosity and permeability. The current study addresses these issues by evaluating the effect of these architectural parameters on oxygen concentration and cell behavior in the interior of scaffolds with different architectures. Cylindrical polycaprolactone (PCL) scaffolds fabricated using precision extrusion deposition and having the same pore size but different porosities and tortuosities, and hence different permeabilities, were statically seeded with MG63 cells. The bases of the scaffolds were sealed with an impermeable layer of PCL and the scaffolds were surrounded with a tubing of low air permeability to allow diffusion of air into the constructs mainly from the top. These constructs were evaluated at days 1 and 7 for cell viability and proliferation as well as oxygen concentration as a function of depth within the construct. A simple mathematical model was used to describe the process of diffusion of oxygen in these cell-seeded scaffolds of varying permeability. It was hypothesized that there would be better diffusion and cell function with increasing permeability. This was found to be true in case of cell viability. However, cell proliferation data revealed no significant differences as a function of depth, day or architecture. Oxygen concentration data revealed trends showing decreasing concentrations of oxygen as a function of depth across all architectures. Tortuosity had a greater influence on oxygen concentration profiles on day 1 compared to porosity, whose effect seemed to dominate on day 7. Overall, porosity seemed to play a greater role than tortuosity in supporting viability, proliferation and oxygen diffusion.