Top-Down and Bottom-Up Engineered Microenvironments for Cartilage Tissue Regeneration

Tyler A Novak, Purdue University

Abstract

Tissue engineering has the potential to mitigate and remedy many degenerative diseases and traumatic injuries. Osteoarthritis, characterized by the structural and biochemical degradation of articular cartilage, affects over 27 million individuals nationwide. The current clinical standard for cartilage repair includes methods such as mosaicplasty and autograft transplantation, where cartilage from non-load bearing regions is used to fill in defects in the cartilage structure. These methods suggest that the complex structure and biochemistry of native cartilage extracellular matrix positively contributes to cartilage healing and regeneration. We investigated this idea through a series of top-down and bottom-up tissue engineering approaches. Using a top-down approach, we studied the healing capability of decellularized cartilage allografts in an in vivo ovine osteoarthritis model. The results of this in vivo study showed positive cartilage healing and supported the model of tissue physicochemical microenvironment as an ideal environment for tissue regeneration. As a result, we investigated a bottom-up approach, attempting to recapitulate various aspects of the native cartilage tissue. In the first study, we investigated the ability of polymerizable collagen fibrils to be aligned in the presence of high magnetic fields, emulating the fibril alignment aspect of the cartilage superficial zone. Further, using a plastic compression approach, we developed gradient collagen structures that emulated the depth dependent alignment properties of articular cartilage while greatly increasing the density and mechanical properties. Finally, we combined the top-down and bottom-up approaches in a unique way to introduce native cartilage signals to a stem cell population. Microparticulated and decellularized cartilage was introduced to collagen-suspended human mesenchymal stem cells in a 3D composite matrix. Additional composites formed from Gu•HCl reductions gave further insight into the contribution of the various ECM components of articular cartilage on the differentiation potential of human MSCs for cartilage regeneration. The culmination of these studies gives unique information on the separation and combination of top-down and bottom-up approaches to tissue engineering in the field of cartilage and osteoarthritis.

Degree

Ph.D.

Advisors

Neu, Purdue University.

Subject Area

Biomedical engineering

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