The influence of the microenvironment on vascularisation of osteochondral tissues

Abstract

The regulation of vascularisation is a major challenge facing osteochondral tissue engineering. Articular cartilage is an avascular tissue and the presence of blood vessels is associated with various pathologies of the tissue. Conversely, bone requires an extensive vascular supply in order to maintain viability and function. Angiogenesis is influenced by aspects of the microenvironment including extracellular matrix molecules and cell secreted factors. In this thesis, in vitro models were used to investigate the effects of glycosaminoglycan content and bone marrow-derived mesenchymal stromal cell secretome on angiogenesis in context to osteochondral tissue. In addition, an in vivo study was used to determine the effect of endocultivation time pre-BMP-2 application on the vascularisation of bone tissue engineered by endocultivation. This thesis has demonstrated that articular cartilage glycosaminoglycans inhibit the adhesion of endothelial cells and suggests this activity is due to chondroitin sulphate and/or hyaluronan. Furthermore, this thesis has also shown that when chondrogenically or osteogenically differentiated, bone marrow-derived mesenchymal stromal cells reduce production of angiogenesis-related proteins and display anti-angiogenic properties in vitro. The results presented in this thesis support the use of endocultivation as a technique for tissue engineering vascularised bone grafts in vivo, however, suggest that increased vascular ingrowth may not necessarily lead to increased bone formation. Together, these findings demonstrate how the cell microenvironment may influence the vascularisation of osteochondral tissue which may have important implications for osteochondral tissue engineering and provide insight into how pathological vascularisation of articular cartilage may occur.