The mechanotransductive and osteogenic responses of bone cells to multiple mechanical and chemical stimuli

William Scott Van Dyke, Purdue University

Abstract

Numerous approaches have been used to understand the biological cues necessary to induce cellular and extracellular matrix (ECM) production for bone tissue engineering purposes, including fluid flow shear stress, aligned ECM substrates, biochemical cues, and surface topography. Numerous factors affect the mechanotransduction process of bone cells to create and manipulate their extracellular matrix including, but not limited to, the extracellular matrix present, the substrate stiffness, and the concentrations of available nutrients. We have designed and characterized a bioreactor that is able to apply fluid shear stress and substrate strain simultaneously to cells in monolayer or in 3D constructs. The goals of this dissertation were threefold: 1) to evaluate the short-term responses of bone cells (bone marrow stromal cells (BMSCs), osteoblasts, and osteocytes) to fluid shear stress, substrate strain, or both of these modes simultaneously, 2) to observe these short-term responses in elevated extracellular levels of calcium and glucose, and 3) to study the long-term osteogenic effects of elevated extracellular levels of calcium and glucose. BMSCs were found to respond best when loading modes were combined, but this response was suppressed in elevated levels of calcium. Osteoblasts and osteocytes both responded best to fluid shear stress alone, but osteocytes in elevated glucose failed to respond to this loading mode. BMSCs were observed to have the highest long-term osteogenesis on kPa-level substrate stiffness and in elevated levels of extracellular calcium. The key findings will have impacts on bone tissue engineering protocol design involving the use of BMSCs and on future mechanotransduction experiments.^

Degree

Ph.D.

Advisors

Eric A. Nauman, Purdue University, Ozan Akkus, Purdue University.

Subject Area

Engineering, Biomedical

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