Exploiting Self-organization in Bioengineered Systems: A Computational Approach

Abstract

The productivity of bioengineered cell factories is limited by inefficiencies in nutrient delivery and waste and product removal. Current solution approaches explore changes in the physical configurations of the bioreactors. This work investigates the possibilities of exploiting self-organizing vascular networks to support producer cells within the factory. A computational model simulates de novo vascular development of endothelial-like cells and the resultant network functioning to deliver nutrients and extract product and waste from the cell culture. Microbial factories with vascular networks are evaluated for their scalability, robustness, and productivity compared to the cell factories without a vascular network. Initial studies demonstrate that at least an order of magnitude increase in production is possible, the system can be scaled up, and the self-organization of an efficient vascular network is robust. The work suggests that bioengineered multicellularity may offer efficiency improvements difficult to achieve with physical engineering approaches.

Directing Multicellular Organization by Varying the Aspect Ratio of Soft Hydrogel Microwells

“…This approach may provide successful solutions to the hotly pursued challenge of vascularizing tissue constructs, implants, and devices with complex and multiscale topographies. [ 70 ] Since our strategy allows highly parallel, reproducible, and cost‐effective hydrogel patterning, we anticipate widespread applications in cell and tissue engineering, cell signaling, and drug discovery. Finally, our discovery that striking differences in multicellular self‐organization are caused by the combined effects of stiffness and microwell aspect ratio is of fundamental importance to understand the role of stiffness in previously observed topography‐ and curvature‐guided cell behaviors.…”

Optimizing bioengineered vascular systems: A genetic algorithm approach

“…Finally, these equations are solved using a linear equation solver to calculate the flow rate Q (i,j) through all the vessels and pressure drop ∆P (i,j) over each vessel [12].…”