Exploring Boundary Effects on Oxygen and Cell Distribution in 3D-Printed Helical Hydrogel: Computational Insights

Developing a functional vascular network within thick hydrogel scaffolds is crucial for efficiently exchanging oxygen and nutrients, removing waste materials, and overall performance of engineered tissues. Recently, 3D bio-printing with coaxial nozzles and sacrificial ink has gained significant attention for creating complex structures with hollow perfusable channels. Current technology cannot evaluate mass transport during vascularization and perfusion of the culture medium into the channels of a porous hydrogel scaffold. Here, a simulation was employed to investigate the effects of boundary conditions on oxygen delivery, cellular growth, and viability within a 3D-printed helical hydrogel using the COMSOL Multiphysics software. Navier-Stokes and Brinkman equations were used to simulate fluid flow in the channel and porous medium, respectively. Concentration boundary condition (uniform oxygen concentration at channel walls) significantly increased the cell density from $2\times 10^{10}\mathrm{~m}^{-3}$ to over $9\times 10^{11}\mathrm{~m}^{-3}$ within one month. The oxygen concentration at the outlet of the concentration boundary condition remained consistently high at $180\mu\mathrm{M}$. However, in the wall boundary condition (no exchange of oxygen at channel walls), the oxygen concentration at the end of the channel fell below the critical threshold for cell survival (14 $\mu\mathrm{M})$. Additionally, the average cell density observed was $1\times 10^{11}\mathrm{~m}^{-3}$. These findings underline the substantial influence of boundary conditions on cell proliferation within the 3D scaffold.