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Advanced 3D Platforms for Modeling CNS Neuroinflammation: Cell Integration, Techniques, and Challenges.
Emmanuelle D Aiyegbusi1,2, Julia Di Stefano1,2, Dearbhaile Dooley1,2
1School of Medicine, University College Dublin, Dublin, Ireland.
Advanced Healthcare Materials
|March 6, 2026
Summary
This review explores advanced 3D cell culture models for studying neuroinflammation, focusing on incorporating diverse central nervous system (CNS) cells and overcoming current limitations for better disease research.
Area of Science:
- Neuroscience
- Immunology
- Biotechnology
Background:
- Neuroinflammation, a CNS immune response, is crucial in neurodegenerative diseases and CNS damage.
- Three-dimensional (3D) cell cultures offer superior capabilities over 2D models for studying complex biological systems.
- Current 3D models face challenges in cell survival, CNS cellular diversity, immune response simulation, scalability, and long-term culture.
Purpose of the Study:
- To review state-of-the-art methods for creating 3D CNS models for neuroinflammation research.
- To explore emerging trends in bioengineering and co-culture strategies for improved model development.
- To guide researchers in selecting effective methodologies for physiologically relevant in vitro models.
Main Methods:
- Incorporation of diverse CNS cell types (neurons, astrocytes, microglia, oligodendrocytes) into 3D models.
- Examination of bioengineering advancements, co-culture techniques, and dynamic systems.
- Critical evaluation of established and innovative protocols for 3D neuroinflammation models.
Main Results:
- 3D models show promise for recapitulating CNS cellular diversity and simulating immune responses.
- Emerging trends focus on enhancing scalability, longevity, and physiological relevance of models.
- Advancements in bioengineering and co-culture strategies are key to overcoming current limitations.
Conclusions:
- Developing advanced 3D models is essential for accurate neuroinflammation research.
- Addressing challenges in cell survival, diversity, and scalability is critical for model efficacy.
- This review provides a framework for selecting and advancing 3D in vitro models for studying neuroinflammation and related CNS disorders.

