Abstract
Cerebral vasculogenesis and angiogenesis are key processes in brain development and disease. However, traditional in vitro models fail to replicate the dynamic microenvironment that regulates vascular responses. This project aims to develop a microfluidic platform to model 3D cerebral microvessels (3D µvessels-on- chip) under controlled perfusion, enabling the study of endothelial differentiation and vascular organization. Human cerebral microvascular endothelial cells (HCMEC/D3) and induced pluripotent stem cell (iPSC)-derived endothelial cells are employed to evaluate vascular maturation under normoxia and hypoxia, the latter being a major driver of pathological angiogenesis in cancer and neurodegenerative disorders. This microfluidic model represents a physiologically relevant tool to dissect mechanisms of cerebral vasculogenesis/angiogenesis and to explore their role in health and disease. It also offers a versatile platform for translational applications, including the evaluation of therapeutic strategies targeting vascular dysfunction.
Objectives
- Objective 1 - Develop a 3D microfluidic model to study cerebral vasculogenesis/angiogenesis under controlled perfusion and with real-time oxygen level mapping.
- Objective 2 – Investigate the effects of hypoxia and shear stress on endothelial cell differentiation and vascular organization.
- Objective 3 – Validate the system using iPSC-derived endothelial cells for enhanced physiological relevance.
Collaborators
- Istituto di Nanotecnologie del CNR (CNR NANOTEC), Lecce
- Istituto per la Microelettronica e Microsistemi del CNR (CNR IMM), Lecce
- Istituto di Neuroscienze del CNR (CNR IN), Milano
Key 5 publications
- 1. 2025, Adv. Health. Mat. (doi: 10.1002/adhm.202401804), “Pericytes-Assisted Vascular Lumen Organization in a Novel Dynamic Human Blood-Brain Barrier-on-chip Model”. Guarino V*, Perrone E, De Luca E., Cesaria M., Zizzari A., Bianco M., Gigli G., Moroni L, Arima V.
- 2. 2025, J. Funct. Biomater. (doi: 10.3390/jfb16080274), "PDMS Membranes Drilled by Proton Microbeam Writing: A Customizable Platform for the Investigation of Endothelial Cell–Substrate Interactions in Transwell-like Devices". Guarino V, Vasco G, Arima V*, Cataldo R, Zizzari A, Perrone E, Gigli G, Cesaria M
- 3. 2025, Polymer Testing (doi: 0.1016/j.polymertesting.2025.108795), “Controlling Endotoxin Contamination in PDMS-Based Microfluidic Systems for Organ-on-Chip Technologies”. Guarino V*, Perrone E, Zizzari A, Bianco M, Rella R, Manera MG, Arima V.
- 4. 2023, Biofabrication (doi: 10.1088/1758-5090/acb571), “Advancements in modelling human blood brain-barrier on a chip”. Guarino V*, Zizzari A, Bianco M, Gigli G, Moroni, Arima V.
- 5. 2021, Materials Today Bio (doi: 10.1016/j.mtbio.2021.100163). “Potential of CO2-laser processing of quartz for fast prototyping of microfluidic reactors and templates for 3D cell assembly over large scale”. Perrone E, Cesaria M, Zizzari A, Bianco M, Ferrara F, Raia L, Guarino V, Cuscunà M, Mazzeo M, Gigli G, Moroni L, Arima V*.
