Modelling the human brainin vitro: biofabrication approaches for neural tissue engineering

Area of Science:

• Neuroscience
• Stem Cell Biology
• Biotechnology

Background:

• Traditional 2D cultures and animal models lack the complexity of the human central nervous system.
• There is a growing need for physiologically relevant human brain models.
• Three-dimensional (3D) systems offer enhanced recapitulation of neural architecture and function.

Purpose of the Study:

• To provide a comprehensive overview of scaffold-free and scaffold-based strategies for generating 3D human brain models.
• To emphasize models derived from pluripotent stem cells.
• To serve as a reference for selecting or developing appropriate in vitro 3D brain models.

Main Methods:

• Review of scaffold-free systems (spheroids, organoids, assembloids) that utilize cell self-organization.
• Review of scaffold-based models using biomaterials (hydrogels, decellularized matrices) to mimic the brain microenvironment.
• Discussion of various fabrication methods, assessing features, strengths, and limitations.

Main Results:

• Scaffold-free systems recreate developmental interactions through intrinsic cell properties.
• Scaffold-based models offer greater control over tissue architecture and reproducibility via biomaterials.
• Key considerations for all methods include scalability, reproducibility, and biological relevance.

Conclusions:

• Both scaffold-free and scaffold-based approaches are advancing the creation of 3D human brain models.
• Pluripotent stem cell-derived models are central to these advancements.
• This review aids researchers in choosing optimal in vitro models for neural development and disease studies.