Navigating Brain Organoid Maturation: From Benchmarking Frameworks to Multimodal Bioengineering Strategies

Area of Science:

• Neuroscience
• Developmental Biology
• Bioengineering

Background:

• Brain organoids offer unique models for human neurodevelopment and disease, recapitulating human-specific processes absent in rodent models.
• Current limitations include slow maturation (≥6 months) and associated tissue degradation, hindering the study of adult-onset disorders and drug screening.
• This necessitates strategies to accelerate organoid maturation beyond conventional culture limitations.

Purpose of the Study:

• To review emerging strategies for accelerating brain organoid maturation.
• To highlight the integration of chronological optimization and bioengineering approaches.
• To provide a roadmap for generating translationally relevant, mature brain organoids.

Main Methods:

• Summarizing recent advancements in brain organoid culture and bioengineering.
• Discussing techniques like vascularized co-cultures for chronological optimization.
• Exploring bioengineering accelerators such as electrical stimulation and microfluidics.

Main Results:

• Emerging strategies can decouple maturation from extended culture times.
• Synergistic integration of optimized culture and bioengineering accelerates functional maturation.
• These approaches address limitations of conventional 3D culturing, reducing metabolic stress and improving tissue homogeneity.

Conclusions:

• Accelerated maturation is achievable through combined chronological and bioengineering strategies.
• Mature brain organoids will enhance modeling of adult-onset neurological disorders and facilitate high-fidelity drug screening.
• This review outlines a path toward more translationally relevant and functionally advanced brain organoid models.