Three-dimensional in vitro tissue culture models of brain organoids

Brain organoids are three-dimensional self-assembled structures that are derived from human induced pluripotent stem cells (hiPSCs). They can recapitulate the spatiotemporal organization and function of the brain, presenting a robust system for in vitro modeling of brain development, evolution, and diseases. Significant advances in biomaterials, microscale technologies, gene editing technologies, and stem cell biology have enabled the construction of human specific brain structures in vitro. However, the limitations of long-term culture, necrosis, and hypoxic cores in different culture models obstruct brain organoid growth and survival. The in vitro models should facilitate oxygen and nutrient absorption, which is essential to generate complex organoids and provides a biomimetic microenvironment for modeling human brain organogenesis and human diseases. This review aims to highlight the progress in the culture devices of brain organoids, including dish, bioreactor, and organ-on-a-chip models. With the modulation of bioactive molecules and biomaterials, the generated organoids recapitulate the key features of the human brain in a more reproducible and hyperoxic fashion. Furthermore, an outlook for future preclinical studies and the genetic modifications of brain organoids is presented.