Tissue-engineering scaffold-based strategies have suffered from limited cell depth viability when cultured in vitro, with viable cells existing within the outer periphery of the fluid-scaffold interface. This is primarily believed to be due to the lack of nutrient delivery into and waste removal from the inner regions of the scaffold construct. This work develops a hydroxyapatite trimodal porous scaffold architecture (i.e., a scaffold providing a discrete domain for cell occupancy and a separate domain for nutrient delivery) through a freeze drying process. Unidirectional channels (500 microm diameter) were incorporated through CNC machining with total combined apparent porosities of 85.1% +/- 0.22%. Effective diffusion coefficients for the bimodal phase (consisting of micro- and meso-pores, without channels) were also determined (7.9 x 10(-10) m(2) s(-1)). Trimodal scaffolds also demonstrated enhanced permeability values (approximately 18-fold increase) compared with bimodal scaffold architectures. In vitro experiments were used to assess initial seeding efficiency and distribution as well as cell viability. The presence of unidirectional channels significantly enhanced initial cell seeding distribution throughout the scaffold depth, while maintaining relatively high seeding efficiencies (67.7% +/- 2.2% for trimodal, 79.1% +/- 2.1% for bimodal scaffolds). Numerical models demonstrated the effectiveness and efficacy of incorporating channels to increase the core oxygen concentration, with the accuracy of these models improved by using experimentally measured cellular oxygen consumption rates and effective diffusion coefficients. The presence of channels had a positive influence in minimizing the concentration gradients compared with bimodal scaffolds for the same cell density distributions.
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