(6cv) Establishing Governing Equations for 3D Cell Culture in Perfusion Bioreactors

My research interests are focused on developing new biomedical products such as biomaterials and bioreactor systems that can be used for drug discovery and testing, 3D cell culture and large tissue regeneration.  Culturing cells and regenerating tissues in vitro on 3D scaffolds involves several challenges, such as efficient nutrient transportation, uniform stress distribution, and the removal of wastes.  Perfusion bioreactors not only allow reproducibility but also provide a controlled environment for production of tissues.  My goal is to establish fundamental governing equations for the design of tissue engineering bioreactors and scaffolds.  My doctoral research involved testing governing equations related to nutrient permeability, mechanical and structural properties of the scaffolds, as well as nutrient consumption kinetics.  The strategy was to use a combination of computational modeling and experimental analysis.  Large scaffolds with a high aspect ratio were utilized so that the obtained experimental measurements have high signal-to-noise ratio.  This allowed the validation of the governing equations used in the computational models with high fidelity.  Three different scaffold preparation techniques, freeze drying, salt leaching, and electrospinning were used to fabricate scaffolds with different microarchitecture.  Chitosan, gelatin, and polycaprolactone polymers were used to prepare scaffolds.  Two types of bioreactor configurations, flow-through and axial-flow, were used in this study.  Both were designed to hold same sized scaffolds, but differ in flow configuration, which made them suitable for evaluating and validating the equations.  Bioreactors of appropriate flow configuration were constructed in-house for experimental analysis.  Computational Fluid Dynamics (CFD) simulations were performed to predict pressure drop, shear stress, deformation, nutrient distribution profile and exit concentration at various operating conditions.  These insights help monitor in vitro tissue regeneration, understand the effect of mechanical stimulus on 3D cell culture, and improve quality of the regenerated tissue.

My future research plan will involve developing a priori charts for designing systems involving porous media can help simplify the design process for bioreactor systems.  The design variables such as flow rate, porosity and permeability can be transformed into dimensionless variables and characteristic curves can be developed to relate these dimensionless variables.  This process will significantly reduce the amount of effort required to improve existing bioreactors and develop new ones.  Further, I plan to establish other governing equations such as nutrient diffusivity in porous media, kinetic parameter, and non-viscoelastic nature of bioscaffolds to help improve our understanding of the tissue regeneration process and better mimic the native tissue growth phenomenon.  Additionally, I would apply my skills and experience from developing the OSU AppCenter at Oklahoma State University in finding ways to use mobile apps to improve productivity of research and development activities.  The poster will include examples of my research projects that constitute my research ideas.  During the session I will give an overview of the potential and challenges associated with my research plan.