Placental vasculopathies are associated with a number of pregnancy‐related diseases, including pre‐eclampsia (PE)—a leading cause of maternal–fetal morbidity and mortality worldwide. Placental presentations of PE are associated with endothelial dysfunction, reduced vessel perfusion, white blood cell infiltration, and altered production of angiogenic factors within the placenta (a candidate mechanism). Despite maintaining vascular quiescence in other tissues, how pericytes contribute to vascular growth and signaling in the placenta remains unknown. Here, pericytes are hypothesized to play a detrimental role in the pathogenesis of placental vascular growth. A perfusable triculture model is developed, consisting of human endothelial cells, fibroblasts, and pericytes, capable of recapitulating growth and remodeling in a system that mimics inflamed placental microvessels. Placental pericytes are shown to contribute to growth restriction of microvessels over time, an effect that is strongly regulated by vascular endothelial growth factor and Angiopoietin/Tie2 signaling. Furthermore, this model is capable of recapitulating essential processes including tumor necrosis factor alpha (TNFα)‐mediated vascular leakage and leukocyte infiltration, both important aspects associated with placental PE. This placental vascular model highlights that an imbalance in endothelial–pericyte crosstalk can play a critical role in the development of vascular pathology and associated diseases.
Blood vessel chips are bioengineered microdevices, consisting of biomaterials, human cells, and microstructures, which recapitulate essential vascular structure and physiology and allow a well‐controlled microenvironment and spatial‐temporal readouts. Blood vessel chips afford promising opportunities to understand molecular and cellular mechanisms underlying a range of vascular diseases. The physiological relevance is key to these blood vessel chips that rely on bioinspired strategies and bioengineering approaches to translate vascular physiology into artificial units. Here, several critical aspects of vascular physiology are discussed, including morphology, material composition, mechanical properties, flow dynamics, and mass transport, which provide essential guidelines and a valuable source of bioinspiration for the rational design of blood vessel chips. The state‐of‐art blood vessel chips are also reviewed that exhibit important physiological features of the vessel and reveal crucial insights into the biological processes and disease pathogenesis, including rare diseases, with notable implications for drug screening and clinical trials. It is envisioned that the advances in biomaterials, biofabrication, and stem cells improve the physiological relevance of blood vessel chips, which, along with the close collaborations between clinicians and bioengineers, enable their widespread utility.
more » « less- NSF-PAR ID:
- 10395358
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials Technologies
- Volume:
- 8
- Issue:
- 7
- ISSN:
- 2365-709X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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