Table 7.

Structural design, functional capabilities, and applications of advanced In Vitro neurobiology models

Pre-Clinical Model	Design & Structural Features	Functional Applications & Capabilities	References
Brain-on-a-Chip	Microfluidic Architecture: Reconstructs the human NVU in vitro using human-derived cells	Physiological Simulation: Simulates blood flow and incorporates relevant disease markers	Lee et al. (2021)
	Integrated Biosensors: Features continuous, real-time monitoring systems for pH, oxygen levels, cytokine release, and nanoparticle distribution	High-Throughput Evaluation: Enables real-time assessment of nanoparticle BBB permeability; provides granular safety and efficacy data	Lee et al. (2021)
3D Bioprinted Brain Tissues	Matrix Composition: Embeds NVU cells within tunable, brain-mimetic 3D matrices, overcoming 2D culture constraints	Phenotypic Preservation: Maintains native glial phenotypes	Lee et al. (2021)
	Perfusable Channels: Utilizes engineered channels to facilitate structural testing and fluid dynamics	Crosstalk & Stress Testing: Recreates essential multicellular crosstalk (e.g., neuron-glia signaling via NF-κB, NLRP3, and cGAS-STING); evaluates BBB integrity under inflammatory stress	Wang et al. (2025d), Aiyegbusi et al. (2026)
	Pathological Triggers: Incorporates specific disease markers (e.g., Aβ or α-synuclein)	Metabolic & Spatial Evaluation: Captures realistic metabolic shifts; allows for the direct spatial evaluation of stimuli-responsive nanocarriers	Qiu et al. (2025), Baghirov (2025), Tang et al. (2025)

2D Two-dimensional, 3D Three-dimensional, Aβ Amyloid beta, BBB Blood–brain barrier, cGAS Cyclic GMP-AMP synthase, NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells, NLRP3 NLR family pyrin domain containing 3, NVU Neurovascular unit, STING Stimulator of interferon genes, α-synuclein Alpha-synuclein