Biofabrication Approaches With Hyaluronic Acid Hydrogels For Cartilage Repair

Current therapies to repair damaged articular cartilage fail to consistently or fully restore the biomechanical function of cartilage. Although cell-based clinical techniques have emerged for the treatment of focal defects in articulating joints, these approaches typically lead to inferior tissue formation when compared to native, healthy cartilage. Alternatively, subchondral microfracture is a surgical procedure that aims to recruit endogenous mesenchymal stromal cells (MSCs) from the underlying bone marrow to facilitate neocartilage formation in focal defects. Similarly, microfracture typically results in the formation of repair cartilage incapable of withstanding the loading environment of the articulating joint over time. New biomaterial-based strategies are therefore in significant demand to improve cartilage tissue formation and maturation within focal defects. Hyaluronic acid (HA) is a glycosaminoglycan that is found in native cartilage and that shows promise as a biomaterial for cartilage tissue engineering due to its innate bioactivity and ability to form hydrogels, water-swollen polymer networks that may be engineered to mimic the native extracellular matrix (ECM). Moreover, hydrogels may be employed as materials for biofabrication, which involves the use of automated additive manufacturing processes such as 3D printing to fabricate living, biological constructs. This dissertation describes the design and implementation of HA hydrogels for the biofabrication of articular cartilage towards improving existing therapies for damaged cartilage. Multiple biofabrication approaches, including extrusion bioprinting, melt-electrowriting, and digital light processing are investigated to engineer scaffolds with rationally designed geometries, mechanical properties, porosities, and biodegradability. Conserved across all these approaches is the use of thiol-ene based photochemistry to control the formation and resultant material properties of HA hydrogels modified with norbornene functional groups. Taken together, the employment of these biofabrication approaches for cartilage repair has significantly informed the design and implementation of future therapies for articular cartilage damage