title: Investigating the role of mechanical and structural properties of scaffolds for cartilage tissue engineering
Creators: name: Sturtivant, Alexander
Publisher: name: The University of Edinburgh
Year: 2024
Subjects: subject: scaffolds
subject: mechanical and structural properties of scaffolds
subject: cartilage tissue engineering
subject: mechanical and structural properties of scaffolds for cartilage tissue engineering
subject: Osteoarthritis
subject: hydrogel system
subject: AlgMa dECMMa based hydrogel system

description: Osteoarthritis is currently measured as the leading cause of disability. It is responsible for significant, social, economic and health costs. With annual healthcare expenditure resulting from osteoarthritis estimated to be as high as $15 Billion. Osteoarthritis is characterised as a disease of the joint, resulting from continuous, unresolved breakdown of articular cartilage. As this damage progresses, the characteristic mechanical properties and function of affected joints is diminished. Eventually, this results in bone-bone contact, which in turn can lead to severe pain, limited mobility and in severe cases, the formation of bony growths that further impinge movement. At present the treatments vary between managing symptoms, using exercise, pharmacological approaches, through to total joint replacement. Neither option offers a long-term treatment, with prolonged pharmacological usage having links to organ damage and addiction, while joint replacements have limited working lifespans. In recent years new approaches have sought to repair traumatic injuries in the cartilage, attributed to osteoarthritis onset. These approaches include methods such as MACI, ACI and osteochondral grafting, which seek to use the patients’ own cells, with tissues from within the joint, or specially designed implants, to regrow the damage. These methods represent the first generation of cartilage tissue engineering used in clinical settings for cartilage repair. They have been shown to offer some pain relief and can enable patients to return to relatively normal levels of activity. However, the cartilage that is formed at their site is typically considered to be mechanically inferior fibrocartilage, which has been attributed to the reports of devices failing in vivo. As a result, the need for developing suitable cartilage tissue engineering devices has remained. Researchers have continued to pursue many avenues to find the right treatment, from cell sources to scaffold architecture. Amongst these approaches have been many attempts to mimic the native articular cartilage properties, however new evidence suggests this may be detrimental to eliciting regenerative behaviour from chondrocytes. Several factors may impact this, including mechanical properties and scaffold architecture. The following work presents a series of investigations into such aspects, and their role in bovine chondrocyte behaviour. Here finite element analysis was performed to characterise the bulk mechanical interplay seen between representative common cartilage tissue engineering materials, and the cartilage of a defect found in the tibio-femoral joint. This was then used in a multiscale workflow to further characterise the impacts of material properties on the microscale, with assessments made of the strains imparted on chondrocytes due to differing scaffold mechanical properties. In both cases it was found that significant changes in bulk tissue stresses and chondrocyte strains can result from differences presented by common scaffolds. To further explore this, a novel AlgMa dECMMa based hydrogel system was developed. This was shown to have tuneable structural and mechanical properties, and to be capable of influencing bovine chondrocyte behaviour in vitro. This material was used as part of a novel static bioreactor experiment, seeking to characterise the variations in transmission of strain between two scaffolds, the role of their compressive properties in this transmission, and the effect this had on bovine chondrocyte behaviour. This showed that under direct load softer scaffolds could impact cell viability, while those with stiffer properties may offer some level of protection. In addition, differences were also seen in matrix production, which may also result from transmitted strains.