4. Applications
4.1 Disease modeling
The lack of suitable in-vitro models to accurately simulate specific tissues and disease states is an important factor restricting basic research and translational research. Organoids reproduce certain characteristics of tissues and organs, opening the door to a new world for disease research and drug development. As we all know, radiotherapy is a common method for cancer treatment, but there are many complications. In patients with head and neck cancer, radiation cause oral mucositis, which leads to loss of taste[74,75]. Radiation was given to taste bud organoids to construct a disease model of oral mucositis, and it was verified by a mouse experiment. The research showed that the results of organoids are consistent with that of the mouse test, that is, the SIRT1 inhibitor nicotinamide significantly relieved oral mucositis[12]. In previous clinical trials conducted in 2016, it was found that BIA 10-2474 (a fatty acid amide hydrolase inhibitor with the potential to treat a variety of neurological diseases) would produce neurotoxic accumulation in humans, but this situation did not occur in experimental animals. ChP organoids derived from human iPSCs also exhibit the toxicity accumulation of BIA 10-2474, indicating that this organoid model is more suitable for toxicity testing of new therapies than experimental animals[76].
Compared with the two-dimensional culture system, organoids help clarify the development, homeostasis, and pathogenesis of diseases and provide possible new approaches for the diagnosis and treatment of diseases. This organoid model was grown in a micro-machined chamber and was used for long-term in-situ imaging. It has been used to simulate cortical folding and study the pathogenesis of encephalopathy[77]. Studies have shown that brain organoids prepared from induced pluripotent stem cells of patients with lissencephaly have mitotic defects in the outer radial glial cells, which are rarely seen in mouse models[78]. Brain organoids are also used to study the Zika virus, which preferentially infects neural progenitor cells and reduces their proliferation and viability. This may be an important reason for the Zika virus to cause head deformities[79]. Talking about neural/stem cell biology, organoids could better track neurons and establish more predictivein-vitro disease models[80]. In regenerative medicine, artificial tissue cultivating was used to establish pathological mechanism research and transplantation research models[81]. Scientists combined with 3D culture organoid technology to develop a type 2 alveolar cell organoid model that could be cultured for a long time without a trophoblast for the development of vaccines and therapies[82]. Then, 3D self-rolled biosensor arrays (3D-SR-BAs) of either active field-effect transistors or passive microelectrodes were implemented to interface human cardiac spheroids in 3D which enabled the development of organ-on-an-electronic-chip (organ-on-e-chip) platform[83] (Figure 5a-b). For taste sensing, bio-artificial tongue devices have been reported to sense comprehensive taste[9]. This is not only a device for taste detection but also provides an effective sensing device to simulate the function of the tongue outside the body, thereby providing a practical basis for exploring the mechanism of taste.