FIGURE 1.

Schematic showing the methods to improve the survival and maturation of brain organoids. Due to the lack of in vivo circulatory system, the progenitor proliferation is reduced over long-term culture. The insufficiency of nutrients and oxygen in the inner part of brain organoids impedes the maturation and differentiation of neurons and glial cells. To promote nutrient and oxygen diffusion, physical mixing is the most common method. Adapting bioengineering methods, including vasculature or scaffolds created by 3D printing and organ-on-a-chip systems such as microfluidics, to brain organoid systems also works. In addition, adapting the organotypic cultures into a brain organoid culture system by slicing organoids to reduce the thickness or further culturing them on an air-liquid interface system could also promote the absorption of oxygen and nutrients. The most essential cause of this problem is that brain organoids lack a functional vascular system. Building functional blood vessels could solve this problem to a large extent. Such strategies include introducing/inducting ECs or implanting them into the mouse brain.