Tissue-Engineered Models of the Human Brain: State-of-the-Art Analysis and Challenges

Abstract

Neurological disorders affect billions of people across the world, making the discovery of effective treatments an important challenge. The evaluation of drug efficacy is further complicated because of the lack of in vitro models able to reproduce the complexity of the human brain structure and functions. Some limitations of 2D preclinical models of the human brain have been overcome by the use of 3D cultures such as cell spheroids, organoids and organs-on-chip. However, one of the most promising approaches for mimicking not only cell structure, but also brain architecture, is currently represented by tissue-engineered brain models. Both conventional (particularly electrospinning and salt leaching) and unconventional (particularly bioprinting) techniques have been exploited, making use of natural polymers or combinations between natural and synthetic polymers. Moreover, the use of induced pluripotent stem cells (iPSCs) has allowed the co-culture of different human brain cells (neurons, astrocytes, oligodendrocytes, microglia), helping towards approaching the central nervous system complexity. In this review article, we explain the importance of in vitro brain modeling, and present the main in vitro brain models developed to date, with a special focus on the most recent advancements in tissue-engineered brain models making use of iPSCs. Finally, we critically discuss achievements, main challenges and future perspectives.

Aligned polycaprolactone/polyaniline electrospun nanofibers for directing neural stem cell differentiation and neuron arrangement

“…In general, these results suggest that fiberbased substrates promoted neuronal differentiation, providing a biomimetic environment for neural cells. Indeed, although the values of Young's modulus in PCL-PANI mats are significantly higher than that of brain tissue, whose elastic modulus ranges from 0.1 to 1 kPa (Tarricone et al, 2022), they can be considered more similar to the one of native tissue compared to glass (~GPa) (Ford and Rajagopalan, 2018). Interestingly, the ratio of neurons to astrocytes was higher for PCL/PANI random mats than aligned ones (Figure 6D).…”

Gut-on-a-Chip Research for Drug Development: Implications of Chip Design on Preclinical Oral Bioavailability or Intestinal Disease Studies

“…When designing a GOC, or choosing from the selection of commercially available GOCs, the so-called spatiotemporal parameters such as the desired culture period and size and shape of the culture chamber should be considered first. For example, when cells are cultured for a longer period of time in combination with mechanical and biochemical cues, cells are able to secrete their own ECM, remodel biomaterial, and differentiate faster into different intestinal cell types (goblet cells, enterocytes, Paneth cells, and neuroendocrine cells) [ 27 , 28 , 29 , 30 ]. However, extensive culture periods also increase the risk on de-differentiation, contamination and the chance on hypoxic or necrotic centers [ 31 , 32 ].…”

The Major Hypotheses of Alzheimer’s Disease: Related Nanotechnology-Based Approaches for Its Diagnosis and Treatment

“…Scaffolds. Nanotechnology also involves developing scaffolds for the tissue engineering of cholinergic neurons [212]. Tissue engineering is based on creating threedimensional structures that can support the growth and function of cells or tissues.…”