Mechanical properties and in vitro modelling of the osteochondral unit

Cooke, Megan Elin (2019). Mechanical properties and in vitro modelling of the osteochondral unit. University of Birmingham. Ph.D.

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Abstract

The osteochondral unit (OCU) comprises bone and cartilage, with a gradient interface between hard and soft tissues. Damage and diseases, such as osteoarthritis (OA), cause irreversible changes to the cartilage matrix. Early, clinically silent, matrix changes in OA were compared to healthy, post-mortem cartilage using mechanical and physicochemical techniques. It was found that degradation of matrix components leaves the superficial region susceptible to mechanical damage. Strategies to repair cartilage damage have focused on replication of the extracellular matrix using hydrogel scaffolds. Alginate is commonly used, and its positive effects on chondrocyte phenotype have been attributed to maintenance of a spherical cell morphology. Here, an alginate fluid gel was formed to enable the non-invasive delivery of chondrocytes. It was found, however, that a spherical morphology was insufficient for maintenance of chondrocyte phenotype and geometric confinement of chondrocytes in alginate played a significant role in phenotypic recovery and stability. Fluid gels were then utilised as support matrices for bioprinting of bi-layered structures to recapitulate the OCU. This support matrix could suspend low-viscosity hydrocolloid solutions prior to crosslinking to co-culture chondrocyte and osteoblast populations in spatially defined regions. Distinct chemical and mechanical environments allowed the maintenance of primary cell phenotypes and function.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):