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[388] and bacterial nanocellulose scaffolds [389] support tissue regeneration and homeostasis of several tissues including cartilage. Besides, in order to secure a viable tissue, scaffolds should facilitate diffusion of oxygen and nutrients, and removal of waste products. Both alginate [89, 388] and bacterial nanocellulose [92, 390] have high swollen 3D architecture, that enables sufficient nutrient diffusion and oxygen transfer to the residing cells. (3) Biocompatibility Scaffold biocompatibility is crucial for the overall success rate of a tissue engineering therapy. Biocompatibility is generally defined as “the ability of a biomaterial to perform with an appropriate host response in a specific situation”. [391] Moreover, scaffold biocompatibility not only depends on the ability to ensure cell viability (i.e. cytotoxicity). It is also the biological response of host tissue to the implanted scaffold material that can induce inflammation along with fibrous encapsulation of the material (i.e. foreign body reaction). The biocompatibility of highly purified alginate (Cellmed, Germany) has already been studied by others and is highly biocompatible both in vitro and in vivo . [251] In fact, alginate is already used for applications such as pharmaceutical applications, microencapsulation technology and wound dressings. [388, 392] The biocompatibility of bacterial nanocellulose was evaluated in chapter eight and more intensively studied by Martínez Ávila et al. according to the standards of ISO 10993. [393] Bacterial nanocellulose scaffold are non-cytotoxic and non-pyogenic. [393] Moreover, after subcutaneous implantation, these scaffolds induce minimal host response. [393] Both alginate and bacterial nanocellulose supported neocartilage formation in vitro and in vivo (this thesis) making them attractive biocompatible scaffolds for the reconstruction of cartilage defect in the head and neck area. Another component of biocompatibility is biomaterial degradation, since the products of degradation can possibly influence biocompatibility in time. Neither alginate nor bacterial nanocellulose degrade, as mammals lack the enzyme alginase or cellulose respectively. They rather slowly dissolve in time. [388, 394] Both alginate [388] and bacterial nanocellulose [389] have shown mild inflammatory response after subcutaneous implantation that decreased in time. Moreover, derivates of these biomaterials have already been used safely as biomedical devices in a clinical application. [395, 396] In conclusion, both alginate and bacterial nanocellulose have characteristics that - at least partially - match the properties of the chondrogenic ECM itself. Alginate has poor biomechanical properties and is typically used as a cell-laden hydrogel, created to encapsulate cells. Infused into a biomechanical stable bacterial nanocellulose scaffold could be an excellent scaffold for future cell-based cartilage repair in the head and neck area. In chapter eight this concept was first introduced, showing that alginate-infused bacterial nanocellulose scaffolds are biocompatible and support neocartilage formation both in vitro and in vivo . Therefore, the combination of alginate and bacterial nanocellulose could provide a potential therapy for the reconstruction of cartilage defect in the head and neck area. Especially, when we could further emerge it to a bioprinting technology as written below. 185 DISCUSSION AND FUTURE PERSPECTIVES 9

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