Biomimetic human small muscular pulmonary arteries

Qianru Jin; Anil Bhatta; Jayson V Pagaduan; Xing Chen; Hoku West-Foyle; Jiayu Liu; Annie Hou; Dan Berkowitz; Scot C Kuo; Frederic B Askin; Thao D Nguyen; David H Gracias; Lewis H Romer

doi:10.1126/sciadv.aaz2598

Biomimetic human small muscular pulmonary arteries

Sci Adv. 2020 Mar 25;6(13):eaaz2598. doi: 10.1126/sciadv.aaz2598. eCollection 2020 Mar.

Authors

Qianru Jin^{1

2}, Anil Bhatta^{1

2}, Jayson V Pagaduan^{1

2}, Xing Chen^{1

2}, Hoku West-Foyle^{3

4}, Jiayu Liu⁵, Annie Hou^{2

6}, Dan Berkowitz^{1

6}, Scot C Kuo^{3

6

4}, Frederic B Askin⁷, Thao D Nguyen^{5

8}, David H Gracias^{2

8}, Lewis H Romer^{1

6

4

9

10}

Affiliations

¹ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
³ Microscope Facility, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁶ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁹ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁰ Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Changes in structure and function of small muscular arteries play a major role in the pathophysiology of pulmonary hypertension, a burgeoning public health challenge. Improved anatomically mimetic in vitro models of these microvessels are urgently needed because nonhuman vessels and previous models do not accurately recapitulate the microenvironment and architecture of the human microvascular wall. Here, we describe parallel biofabrication of photopatterned self-rolled biomimetic pulmonary arterial microvessels of tunable size and infrastructure. These microvessels feature anatomically accurate layering and patterning of aligned human smooth muscle cells, extracellular matrix, and endothelial cells and exhibit notable increases in endothelial longevity and nitric oxide production. Computational image processing yielded high-resolution 3D perspectives of cells and proteins. Our studies provide a new paradigm for engineering multicellular tissues with precise 3D spatial positioning of multiple constituents in planar moieties, providing a biomimetic platform for investigation of microvascular pathobiology in human disease.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Algorithms
Biomarkers
Biomimetics*
Cells, Cultured
Coculture Techniques
Humans
Mechanical Phenomena
Models, Theoretical
Muscle, Smooth*
Myocytes, Smooth Muscle / metabolism
Pulmonary Artery*
Signal Transduction
Tissue Engineering* / methods

Substances

Biomarkers

Grants and funding

S10 OD016374/OD/NIH HHS/United States