Development of Extracellular Matrix Based Biomaterials for Articular Cartilage Repair

Barthold, Jeanne

Graduate Thesis Or Dissertation

Development of Extracellular Matrix Based Biomaterials for Articular Cartilage Repair Público Deposited

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Citeable URL: https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/xd07gt86p

Abstract

Osteoarthritis, a degenerative joint condition prevalent in the knee joint, affects over 350 million people. Following injury to articular cartilage, disease progression can be exponential; there is a significant need to develop materials that can repair cartilage defects to delay or inhibit total joint degradation. Despite decades of research, the unique architecture and function of articular cartilage is difficult to replicate, and many engineered biomaterials fail to integrate with surrounding tissue. Allografts are one of the most successful interventions, involving transplantation of osteochondralsections from a recently deceased donor to the injured defect. While allografts show promising long-term clinical data, they suffer extreme source limitations.

This thesis aims to develop extracellular matrix (ECM) based scaffolds that balance cellularity, integration, structural stability, and tissue complexity. Motivated by the success of allografts, we decellularize and evaluate an animal-derived allograft by implanting it into a sheep knee for 6 months. In this study, presented in chapter 2, acellular allografts restored native function, structural composition, surface tribology, and promoted tissue integration. Unfortunately, despite high cellularity in integration regions, few cells migrate into the allograft. In chapter 3, to address the limitations of allograft cellularity, we engineered a new scaffold by pulverizing acellular ECM into microparticles and packing particles together in a hydrogel. In vitro analysis of our scaffold shows that when particles are tightly packed, the modulus increases rapidly from 50kPa to over 300kPa, recapitulating the acellular allograft moduli. In cellularity studies, when chondrocytes were introduced, they migrated into microparticles and expressed genes consistent with cartilage repair. In chapter 4, having overcome the limitations of the acellular allograft by engineering a scaffold which enabled cell migration, we aimed to further mimic native cartilage by creating tissue layers. To achieve a layered scaffold, we developed a 3D-printable bioink that maintained the packed tissue particle design from chapter 3. We printed a two-layer scaffold using the bioink: a mid-deep cartilage zone printed under a superficial zone, together recapitulating the compressive modulus and tribological properties of native tissue. We also demonstrated proof-of-concept printing of custom shapes, resulting in a potentially powerful clinical intervention for articular cartilage repair.

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