15502-m-pleumeekers

THESIS AIM AND OUTLINE Cartilage tissue engineering can offer promising solutions for restoring cartilage defects in the head and neck area and has potential to overcome limitations of current treatments. The primary objective of this thesis is to ultimately improve cartilage regeneration and develop an one-step surgical therapy for the repair of facial cartilage defects. Therefore, I focus on the generation of a cell-based cartilaginous framework and evaluate the suitability of cells or combination of cells on natural scaffolds . Based on my objectives, the following research questions were formulated: Q1 What are the biomechanical and biochemical characteristics of native facial cartilages (i.e. ear and nasal cartilages)? Q2 Which cells or combination of cells are most suitable for cell-based cartilage repair in the head and neck area? Q3 Which natural scaffolds (i.e. alginate, bacterial nanocellulose, decellularized ECM) are a suitable candidate for future cell-based cartilage repair in the head and neck area? Ideally, tissue-engineered cartilage should possess similar biomechanical and biochemical properties to the native tissue. Chapter two and three establish a precise biomechanical and biochemical characterization of native human ear and nasal cartilages (i.e. nasoseptal and alar cartilages) in order to set a benchmark against which to evaluate cartilage tissue engineering attempts. For successful cell-based cartilage repair in the head and neck area, selection of an appropriate cell source is crucial. In chapter four , the performance of culture-expanded chondrocytes and MSCs from several anatomical locations (i.e. chondrocytes derived from ear, nose and joint, and MSCs derived from adipose tissue and bone marrow) is evaluated. Culture-expansion has however certain disadvantages: (1) it results in chondrocyte dedifferentiation, which usually results in fibrous and mechanically inferior cartilaginous tissue; (2) it requires a two-step surgical procedure. As the basic principle for the development of a one-step surgical repair procedure, co-cultures of primary chondrocytes and MSCs is further elucidated in chapter five and six . Chapter five describes the trophic effect of AMSCs or BMSCs on chondrocytes and whether their effect is origin-dependent or a general MSC- characteristic. Chapter six evaluates the use of ECs and NCs in combination with BMSC for their use in future one-step cell-based cartilage repair in the head and neck area. For successful cartilage regeneration, the properties of the 3D scaffold are of equivalent importance. Scaffold design should herein substitute for the cell natural environment providing instantaneous cell support and guiding tissue development and remodelling. Intuitively, native ECM has the potential to be the most ideal scaffold for tissue engineering and regenerative therapies. Preservation of native ECM is best retained through the process of decellularization. C hapter seven displays the preparation of decellularized cartilage scaffolds and extensively characterize their biochemical and biomechanical properties, as well as investigate their cytocompatibility. 1 THESIS AIM AND OUTLINE 21