PMID- 38008744 OWN - NLM STAT- MEDLINE DCOM- 20231128 LR - 20231129 IS - 2045-8118 (Electronic) IS - 2045-8118 (Linking) VI - 20 IP - 1 DP - 2023 Nov 27 TI - Microfluidic models of the neurovascular unit: a translational view. PG - 86 LID - 10.1186/s12987-023-00490-9 [doi] LID - 86 AB - The vasculature of the brain consists of specialized endothelial cells that form a blood-brain barrier (BBB). This barrier, in conjunction with supporting cell types, forms the neurovascular unit (NVU). The NVU restricts the passage of certain substances from the bloodstream while selectively permitting essential nutrients and molecules to enter the brain. This protective role is crucial for optimal brain function, but presents a significant obstacle in treating neurological conditions, necessitating chemical modifications or advanced drug delivery methods for most drugs to cross the NVU. A deeper understanding of NVU in health and disease will aid in the identification of new therapeutic targets and drug delivery strategies for improved treatment of neurological disorders.To achieve this goal, we need models that reflect the human BBB and NVU in health and disease. Although animal models of the brain's vasculature have proven valuable, they are often of limited translational relevance due to interspecies differences or inability to faithfully mimic human disease conditions. For this reason, human in vitro models are essential to improve our understanding of the brain's vasculature under healthy and diseased conditions. This review delves into the advancements in in vitro modeling of the BBB and NVU, with a particular focus on microfluidic models. After providing a historical overview of the field, we shift our focus to recent developments, offering insights into the latest achievements and their associated constraints. We briefly examine the importance of chip materials and methods to facilitate fluid flow, emphasizing their critical roles in achieving the necessary throughput for the integration of microfluidic models into routine experimentation. Subsequently, we highlight the recent strides made in enhancing the biological complexity of microfluidic NVU models and propose recommendations for elevating the biological relevance of future iterations.Importantly, the NVU is an intricate structure and it is improbable that any model will fully encompass all its aspects. Fit-for-purpose models offer a valuable compromise between physiological relevance and ease-of-use and hold the future of NVU modeling: as simple as possible, as complex as needed. CI - (c) 2023. The Author(s). FAU - Wevers, Nienke R AU - Wevers NR AD - MIMETAS BV, De Limes 7, Oegstgeest, 2342 DH, The Netherlands. n.wevers@mimetas.com. FAU - De Vries, Helga E AU - De Vries HE AD - Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam Neuroscience - Neuroinfection and Neuroinflammation, De Boelelaan 1117, Amsterdam, the Netherlands. LA - eng GR - 667375/Horizon 2020/ GR - 813294/Horizon 2020/ PT - Journal Article PT - Review DEP - 20231127 PL - England TA - Fluids Barriers CNS JT - Fluids and barriers of the CNS JID - 101553157 SB - IM MH - Animals MH - Humans MH - *Microfluidics MH - Endothelial Cells MH - Blood-Brain Barrier/metabolism MH - Brain/blood supply MH - *Nervous System Diseases PMC - PMC10680291 OTO - NOTNLM OT - Blood-brain barrier OT - In vitro models OT - Microfluidics OT - Neurovascular unit OT - Organ-on-a-chip COIS- Nienke R. Wevers is an employee of MIMETAS BV, which markets the OrganoPlate. EDAT- 2023/11/27 00:43 MHDA- 2023/11/28 06:42 PMCR- 2023/11/27 CRDT- 2023/11/26 23:33 PHST- 2023/07/14 00:00 [received] PHST- 2023/11/15 00:00 [accepted] PHST- 2023/11/28 06:42 [medline] PHST- 2023/11/27 00:43 [pubmed] PHST- 2023/11/26 23:33 [entrez] PHST- 2023/11/27 00:00 [pmc-release] AID - 10.1186/s12987-023-00490-9 [pii] AID - 490 [pii] AID - 10.1186/s12987-023-00490-9 [doi] PST - epublish SO - Fluids Barriers CNS. 2023 Nov 27;20(1):86. doi: 10.1186/s12987-023-00490-9.