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Engineering A Mimetic Environment For Articular Cartilage Production
Dissertation

Engineering A Mimetic Environment For Articular Cartilage Production

Terreill Joseph Robertson
Doctor of Philosophy (PhD), Washington State University
12/2025
DOI:
https://doi.org/10.7273/000008395
pdf
2025-Robertson final dissertation draft5.40 MB
Embargoed Access, Embargo ends: 02/26/2027 CC BY-ND V4.0

Abstract

Biomanufacturing Bioreactor Cartilage Chondrogenesis Stem Cell Cell Differentiation
Human articular cartilage (AC), an anisotropic tissue lining the subchondral bone, functions to regularly resist deformational changes applied by daily activities such as walking, running, and more. Upon joint loading, a myriad of mechanical stresses and strains arise. Hydrostatic pressure is one of many mechanical factors that emerge from compression of the hydrated tissue that contains negatively charged proteoglycan that entraps water into the tissue matrix. Fluid shear stress is another mechanical loading type that is well represented from viscous synovial shears at AC surface as well as by interstitial fluid shears distributed throughout the tissue thickness. Modulation of these mechanical stimuli leads to a strengthened extracellular matrix (ECM) enriched with key proteins such as type II collagen and aggrecan that are resistive to mechanical straining. Innovative treatment options for osteoarthritis, characterized by articular cartilage (AC) degradation, are emerging through cartilage tissue engineering strategies. An essential feature in this field involves mimicking the cell microenvironment which provides cues for cell growth, fate, and role. This dissertation is focused on creating a similar AC hydrodynamic environment equipped with providing gradated fluid shear and oscillating hydrostatic pressure stimulation to address how mechanical signals influence cell differentiation. First, we assessed how gradated fluid shears created by our novel tapered bioreactor design regionally influences mesenchymal stromal cells (MSC) to commit to a chondrogenic lineage. We then conducted another fluid perfusion experiment to evaluate how the synthesized ECM produced by MSC and articular chondrocyte (AChs) co-cultures compare to ACh monocultures to understand how both cell models behave under perfused conditions. In a final effort to engineer a representative AC microenvironment, a bioreactor study containing a combination of OHP and fluid shear stress was performed to enhance cell chondrogenesis and ECM formation.

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