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Bioprinting Recent developments in 3D bioprinting have brought immense excitement to the field of tissue engineering. In 3D bioprinting, scaffold biomaterials and living cells are accurately deposited in a layer-by-layer fashion. [397] Thereby, 3D bioprinting has the ability to control spatial placement of living cells relative to their neighboring cells or scaffold environment. Which in turn provides the ability to recreate the complexity of living tissues that mimic natural micro-architecture of the targeted tissue itself. The primary printing technology used for tissue engineering purposes is inkjet “drop-on-demand” bioprinting. [398] Essentially, inkjet bioprinting technology is based on digitally controlled ejection of drops of “bioink” from a print head onto a substrate. These bioinks are the building blocks of the regenerated tissue and contain livings cells and/or scaffold biomaterials. [399] Both alginate [400, 401] and bacterial nanocellulose [402, 403] have been demonstrated to be excellent bioinks for 3D bioprinting purposes. They have shown good printability [400, 404] and high biocompatibility [400, 405]. So far, the clinical application of inkjet bioprinting has only sparsely been applied in the field of cartilage regeneration. [402, 404, 406] 3D bioprinting gives the opportunity to tissue engineer complex 3D tissues with high reproducibility, making it a very promising technique for the reconstruction of cartilage defects in the head and neck area. Future perspectives Over the past decades, there has been significant progress in the treatment of cartilage defects using tissue engineering strategies. Recently, the field is slowly changing from bench to bedside with a number of clinical and preclinical studies ongoing worldwide. (reviewed by Huang et al . [118]) However, these studies basically involve cell-based articular cartilage repair instead of the regeneration of cartilage defects in the head and neck area. Such translational research necessitates governmental oversight that guards efficacy and safety of innovative cell-based therapies in order to protect and guarantee public health. Ultimately, an one-step surgical therapy is preferred for the reconstruction of cartilage defects in the head and neck area. Regulatory aspects of clinical application The European Medicines Agency (EMA) and the Food and Drug Administration (FDA) are responsible for the surveillance and evaluation of medicinal products and devices in the European Union and United States respectively. However, the lack of a regulatory framework for tissue-engineered products (TEPs) has significantly impeded the translation of tissue engineering therapies to clinical application. [407] The introduction of Advanced Therapy Medicinal Products (ATMPs) in the European Union [408] and Human Cells and Tissues and Cellular- and Tissue-Based Products (HCT/Ps) in the United States [409], have substantially contributed to global biotechnology market growth [410] and provide a legitimate tool for overseeing TEPs. At present, only few cell-based therapies are awarded marketing authorization by the EMA or FDA. [410, 411] Of these TEPs, Carticel TM , ChondroCelect® and MACI® are the only licensed therapies for the reconstruction of cartilage defects. These advanced technologies are however entirely focused on the reconstruction of articular 186 CHAPTER 9

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