Fine-tuning Cartilage Tissue Engineering by Applying Principles from Embryonic Development

Cartilage has a very poor capacity for regeneration in vivo. In head and neck surgery cartilage defects are usually reconstructed with autologous cartilage from for instance the external ear or the ribs. Cartilage tissue engineering may be a promising alternative to supply tissue for cartilage reconstructions in otorhinolaryngology as well as in plastic surgery and orthopaedics. The aim of this thesis is to find new tools by which cartilage tissue engineering can be better controlled. In head and neck surgery it is important that tissue engineered cartilage is stable and does not mineralize when used for cartilage reconstructions. Therefore, in this thesis our primary focus was the generation of cartilage of a hyaline phenotype that does not mineralize when implanted in vivo. For this purpose we studied expanded chondrocytes and adult bone-marrow derived mesenchymal stem cells (BMSC). We hypothesize that new insights for cartilage tissue engineering can be gained by studying in-vivo cartilage development during embryonic development. As these processes may involve similar pathways, understanding these common pathways may lead to advances in cartilage tissue engineering. We concentrated on two growth factor signaling pathways known to be important for cartilage development: TGF-β and FGF. As a background for the research in this thesis we will discuss the following topics in this general introduction: cartilage, cartilage defects in head and neck surgery, cartilage tissue engineering, embryonic chondrogenesis, and growth factors influencing chondrogenesis. We will conclude the general introduction with the aim and outline of this thesis.

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