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Understanding this mechanism is important for advancing research into neurodegenerative diseases and trauma\u2010induced CNS damage. Three\u2010dimensional (3D) cell culture models offer enhanced structural and functional capabilities compared to traditional 2D models, yet their implementation remains challenging. Key limitations include cell survival, faithful recapitulation of CNS cellular diversity, simulation of immune responses, and issues of scalability and long\u2010term culture. This review explores state\u2010of\u2010the\u2010art methods for incorporating neurons, astrocytes, microglia, oligodendrocytes, and other CNS\u2010relevant cell types into 3D models to study neuroinflammation. Additionally, it examines emerging trends in bioengineering, co\u2010culture strategies, and dynamic systems that improve model scalability and longevity. 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