Biomechanical assessment of extracellular matrix in native and tissue engineered cartilage across lenght scales

Abstract

Musculoskeletal diseases (MSD) and related disorders account for the largest fraction of temporary and permanent disabilities, and are often considered to be an inevitable consequence of aging. In developed countries, these diseases are responsible for more than half of all chronic conditions suffered by people over the age of 50. In particular, osteoarthritis (OA) is among the leading causes of chronic MSD and the most common joint disorder in the EU. To maintain a normal active lifestyle for patients suffering from OA, the associated costs and the need for effective treatments are very high. For example, more than 45 million people in the US currently have osteoarthritis and it is also the most common joint disorder in EU societies. To date, there is no optimal diagnostic procedure and no permanent cure. OA is usually detected at the level where treatment options are very limited. Thus, the management of OA largely relies on controlling the pain and symptoms through medical therapy that involves medication and rehabilitation exercises. However, if such treatments are inadequate, surgical procedures are necessary e.g. osteotomy or joint replacement to relieve pain and increase joint functions in patients with OA. One promising option involves the implantation of functional cartilage grafts. These are engineered using autologous cells harvested from a small cartilage biopsy and cultured into porous biodegradable scaffolds. Nevertheless, tissue engineered cartilage (TEC) is not used in routine clinical practice because of the variability of the tissue properties (e.g. using cells from different donors) and lack of reliable quality controls. The above mentioned issues generally stem from a limited mechanistic understanding of cartilage function. This has been driving impetus of this work to seek deeper fundamental insight into the functional properties of cartilage and the development of OA. By integrating state-of-the-art technologies, the overarching objective of this MD-PhD is to obtain a biomechanical assessment of the extracellular matrix in native and TEC spanning from the molecular length scale to the tissue level.