Modelling and Optimization of Fluid Dynamics, Microparticles and Cell Loading in Microfluidics

Organ-on-a-chip technology allows for the examination of cell cultures within dynamic systems to better understand biological pathways. The three-dimensional (3D) microenvironment in which cells reside influences their behavior and maturation via mechanobiological cues. Computational fluid dynamics can be used to model the incorporation of biomaterials and 3D constructs as well as in the spreading of cells in microfluidic devices. In our work poly(lactic acid) microparticles (MPs) are used as 3D substrate for mesenchymal stem cells (MSCs) for cancer research within the bone. Computational fluid dynamics (CFDs) was used to predict the behavior of MPs when loaded in microfluidic devices and define the optimal density for cell growth. Predicted efficiency of loading aligned with the observed MPs loaded in the microfluidic devices. A final concentration of 1,160 MPs/μL was then chosen as demonstrated to support the growth of MSCs. This work demonstrates the feasibility of using computational modelling to optimize microfluidic design and particles loading, and to assess the use of biomaterials prior to the undertaking of extensive time-consuming laboratory work in a microfluidic system.

I. Introduction

The development of microfluidic devices to generate organ-on-a-chip (OOAC) platforms, allows for the culture of cells within a dynamic and complex 3D environment. Such advances have allowed for the development of highly complex models which can be used in biomedical research, drug discovery, as well as pre-clinical testing including those modelling the bone [1 - 3]. OOACs aim to recapitulate biomechanical cues within tissue micro-environment, such as topography and flow due to their effect on cell behavior and differentiation [4]. Topography is the microscopic surface features that cells interact with and is determined by the hierarchical structure of the ECM and roughness [5]. Interstitial flow is the movement of fluid through the extracellular matrix of tissues [6].