4-D Flow Control in Porous Scaffolds: Toward a Next Generation of Bioreactors

Tissue engineering (TE) approaches that involve seeding cells into pre-determined tissue scaffolds ignore the complex environment where the material properties are spatially inhomogeneous and evolve over time. We present a new approach for controlling mechanical forces inside bioreactors, which enables spatiotemporal control of flow fields in real time. Our adaptive approach offers the flexibility of dialing-in arbitrary shear stress distributions and adjusting flow field patterns in a scaffold over time in response to cell growth without needing to alter scaffold structure. This is achieved with a multi-inlet bioreactor and a control algorithm with learning capabilities to dynamically solve the inverse problem of computing the inlet pressure distribution required over the multiple inlets to obtain a target flow field. The new method constitutes a new platform for studies of cellular responses to mechanical forces in complex environments and opens potentially transformative possibilities for TE.