5de Optimization of 3D Porous Scaffold Structure for Favorable Fluid Shear and Nutrient Transport Inside a Perfusion Bioreactor

Roman S. Voronov, School of Chemical, Biological, and Materials Engineering, University of Oklahoma, 100 E. Boyd, SEC Room 311, Norman, OK 73019, Samuel VanGordon, Bioengineering, University of Oklahoma, 100 E. Boyd St., SEC T-335, Norman, OK 73019, Dimitrios Papavassiliou, Chemical Engineering, University of Oklahoma, Sarkeys Energy Center, 100 East Boyd Street, Norman, OK 73019, and Vassilios I. Sikavitsas, Chemical, Biological, and Materials Engineering, University of Oklahoma, 100 E. Boyd St., SEC Room T335, Norman, OK 73019.

Due to their degradation characteristics and mechanical properties biodegradable synthetic polymer scaffolds, such as Poly-L-lactic acid (PLLA) which is used in this study, seeded with osteoblastic cells have emerged as potential replacement therapies for damaged or lost bone tissue. The goal of this work is to optimize PLLA biomimetic 3D scaffold structure for enhanced tissue regeneration with three targets in mind: maximized solid-fluid contact area for increased cell adhesion, efficient nutrient transport to osteoblastic cells inside the scaffold for promotion of cell survival and favorable internal stresses inside the scaffold pores for stimulated proliferation. 3D microarchitecture of the scaffolds is characterized using microtomographic (µCT) analysis with a 10µm resolution. Laminar flows of osteogenic media through the cell-seeded cylindrical scaffolds in a flow perfusion bio-reactor are modeled via Lattice Boltzmann Method (LBM) fluid dynamics simulations. High performance computing in conjunction with a house hybrid MPI/Open MP parallelized scheme is employed in order to take advantage inherent LBM parallelizability. Macroscopic mass transfer in the macro-scale is modeled using the Lagrangian Scalar Tracking (LST) method: the motion of scalar markers is decomposed into a convection part (velocity field obtained from LBM simulations) and a diffusion part (Brownian motion obtained from a mesoscopic Monte-Carlo approach). Velocity field and internal stress distribution fields, and parametric nutrient transport study results are presented as a part of this work. Additionally, effects on the bone tissue regenaration of varying the internal scaffold geometry as well as that of the pressure force driving the flow through the scaffold are explored in detail. The study as performed at different time points throughout a two week culturing point. The theoretical framework developed allows for improved tissue generation via: maximum solid-fluid contact area for uniform cell adhesion, efficient nutrient and waste transport inside the scaffolds for promotion of cell survival and favorable mechanical stimulation of cell proliferation.