Maintaining cell depth viability: on the efficacy of a trimodal scaffold pore architecture and dynamic rotational culturing

Tissue-engineering scaffold-based strategies have suffered from limited cell depth viability when cultured in vitro with viable cells typically existing at 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 focused on the assessment of a hydroxyapatite multi-domain porous scaffold architecture (i.e. a scaffold providing a discrete domain for cell occupancy and a separate domain for nutrient delivery). It has been demonstrated that incorporating unidirectional channels into a porous scaffold material significantly enhanced initial cell seeding distribution, while maintaining relatively high seeding efficiencies. In vitro static culturing showed that providing a discrete domain for nutrient diffusion and metabolic waste removal is insufficient to enhance or maintain homogeneous cell viability throughout the entire scaffold depth during a 7-day culture period. In contrast, scaffolds subjected to dynamic rotational culturing maintained uniform cell viability throughout the scaffold depth with increasing culturing time and enhanced the extent of cell proliferation (~2–2.4-fold increase) compared to static culturing.