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cartilage defects. So far, no TEPs have been authorized for the treatment of cartilage defects in the head and neck area. The manufacturing of TEPs that comply EMA or FDA guidelines require good manufacturing practices (GMP) [412] along with good laboratory practices and good clinical practices. As defined, GMP-protocols cover practically all aspects of product manufacturing and “ensure that products are consistently produced and controlled to the quality standards appropriate to their intended use”. [412, 413] Process performance and product quality are all comprised in GMP-protocols, including the training of qualified personnel, the validation and control of materials and procedures, the identity and sterility of the equipment, facility requirements, product traceability and reproducibility. Considering this, the translation of fundamental cell-based therapy into clinical product following GMP-guidelines is very challenging. Therefore, understanding and recognition of the regulatory environment early in the development of a cell-based therapy is critical for the overall success of TEPs. Translation towards a cell-based therapy Tissue engineering strategies could technically simplify and thereby improve the surgical treatment of cartilage defect in the head and neck area. Although our research could not directly translate towards a clinical cell-based therapy, it has identified potential for future translational research. First, the combination of chondrocytes and MSCs has held great promise for cell-based cartilage repair in the head and neck area. For implementation of such therapy, an optimal cell density and ratio of MSCs to chondrocytes is imperative. Puelacher et al. already recommended cell densities greater than 20x10 6 cells per milliliter. [239] That means that for the reconstruction of - for example - the ear, one should require 140x10 6 cells in total, assuming that the volume of adult ear cartilage comprises approximately 7 milliliter (data not shown). Using only 20% primary chondrocytes (at a MSC-chondrocyte ratio of 4:1) as described previously, [74, 246] a feasible amount of 28x10 6 chondrocytes and 112x10 6 MSCs are necessary. However, no consensus on optimal co-culture ratios is yet available. Future research needs to clarify if we could increase cell density while further reduce the number of primary chondrocytes without inhibiting cartilage matrix production and stability. In the translation towards a cell-based therapy, the selection of a scaffold is crucial as stated before. Recent advances in the field of cartilage tissue engineering have been driven from “cell-based” towards “cell-free” regenerative therapies. [414] Acellular biomaterials mimic native ECM and thereby attract native progenitor cells to migrate into the biomaterial and trigger chondrogenic differentiation. To date, acellular biomaterials have shown promising regenerative effects on various tissues (Acellular biomaterials: an evolving alternative to cell-based therapies. Burdick. 2013) including articular cartilage [415]. However, it is less likely that these acellular biomaterials have similar effect on cartilage defects in the head and neck area, as native progenitor cells are generally missing (i.e. congenital, trauma, cancer) or genetically diseased (i.e. congenital remnants). Therefore, for future cell-based cartilage repair in the head and neck area a cellular 3D scaffold that - at least partially - mimics structural and functional characteristics of native tissue microenvironment is imperative. In conclusion, this thesis has focussed on the generation of a tissue-engineered cartilaginous framework for the reconstruction of cartilage defects in the head and neck area 187 DISCUSSION AND FUTURE PERSPECTIVES 9