A prediction of cell differentiation and proliferation within a collagen–glycosaminoglycan scaffold subjected to mechanical strain and perfusive fluid flow

• Published in: Journal of biomechanics 2010-03, Vol.43 (4), p.618-626
• Main Authors: Stops, A.J.F, Heraty, K.B, Browne, M, O'Brien, F.J, McHugh, P.E
• Format: Article
• Language: English
• Subjects: Animals; Architecture; Biological and medical sciences; Bioreactors; Biotechnology; Cell Differentiation; Cell Proliferation; Cells, Cultured; Collagen - chemistry; Collagen–glycosaminoglycan scaffold; Computational fluid dynamics; Computer Simulation; Computerized, statistical medical data processing and models in biomedicine; Deformation; Differentiation; Finite Element Analysis; Fluid flow; Fluids; Fundamental and applied biological sciences. Psychology; Glycosaminoglycans - chemistry; Health. Pharmaceutical industry; Humans; Industrial applications and implications. Economical aspects; Inlets; Mechanotransduction, Cellular - physiology; Medical sciences; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - physiology; Miscellaneous; Models and simulation; Models, Biological; Perfusion - instrumentation; Perfusion bioreactor; Physical Medicine and Rehabilitation; Porous materials; Scaffolds; Strain; Studies; Tissue Engineering; Tissue Scaffolds
• ISSN: 0021-9290; 1873-2380
• DOI: 10.1016/j.jbiomech.2009.10.037

Abstract Mesenchymal stem cell (MSC) differentiation can be influenced by biophysical stimuli imparted by the host scaffold. Yet, causal relationships linking scaffold strain magnitudes and inlet fluid velocities to specific cell responses are thus far underdeveloped. This investigation attempted to simulate cell responses in a collagen–glycosaminoglycan (CG) scaffold within a bioreactor. CG scaffold deformation was simulated using μ-computed tomography (CT) and an in-house finite element solver (FEEBE/ linear ). Similarly, the internal fluid velocities were simulated using the afore-mentioned μCT dataset with a computational fluid dynamics solver (ANSYS/CFX). From the ensuing cell-level mechanics, albeit octahedral shear strain or fluid velocity, the proliferation and differentiation of the representative cells were predicted from deterministic functions. Cell proliferation patterns concurred with previous experiments. MSC differentiation was dependent on the level of CG scaffold strain and the inlet fluid velocity. Furthermore, MSC differentiation patterns indicated that specific combinations of scaffold strains and inlet fluid flows cause phenotype assemblies dominated by single cell types. Further to typical laboratory procedures, this predictive methodology demonstrated loading-specific differentiation lineages and proliferation patterns. It is hoped these results will enhance in-vitro tissue engineering procedures by providing a platform from which the scaffold loading applications can be tailored to suit the desired tissue.