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and has identified potential for future translational research. For cell source selection, we recommend to use location and type-specific chondrocytes. Interestingly, 80 percent of chondrocytes can be replaced by MSCs without influencing cartilage matrix production nor stability. Thereby, the use of primary cells is warranted, as MSCs can be obtained relatively easy in larger numbers. In this co-culture procedure, a general trophic or immunomodulatory role is provided by MSCs. For scaffold selection, we recommend to use a 3D scaffolds that mimic natural micro-architecture of the 3D ECM of the targeted tissue itself. Although decellularized scaffolds are intuitively the most ideal scaffold for tissue engineering therapies, their application seems currently mainly valuable for research purposes and not yet for clinical application in the head and neck area. Therefore, we have focussed on natural matrix-inspired scaffolds (i.e. alginate and bacterial nanocellulose). Both alginate and bacterial nanocellulose have characteristics that - at least partially - match the properties of the chondrogenic ECM itself. The combination of alginate and bacterial nanocellulose could provide a potential therapy for the reconstruction of cartilage defect in the head and neck area. 188 CHAPTER 9