Evidence map›Paper›PMID 29751516›Full record

ArticleNanomaterials (Basel, Switzerland)2018

Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics.

Dewy C van der Valk, Casper F T van der Ven, Mark C Blaser, Joshua M Grolman, Pin-Jou Wu, Owen S Fenton, Lang H Lee, Mark W Tibbitt, Jason L Andresen, Jennifer R Wen and 11 more

Open access · goldAbstract read
In one paragraph

Article in Nanomaterials (Basel, Switzerland), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
8.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Bioprinting of Cardiac Tissue in Space: Where Are We?Advanced healthcare materials · 2023
    Article
  13. Article
  14. Article
  15. Article
  16. Network-Guided Multiomic Mapping of Aortic Valve Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2023
    Review
  17. Latest Advances in 3D Bioprinting of Cardiac Tissues.Advanced materials technologies · 2022
    Article
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 3 countries.

Dewy C van der ValkCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. dewyvdvalk@gmail.com.
Casper F T van der VenCenter of Excellence in Cardiovascular Biology, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Woman's Hospital, Harvard Medical School, Boston, MA 02115, USA. c.f.t.vanderven@umcutrecht.nl.
Mark C BlaserCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. mblaser@bwh.harvard.edu.
Joshua M GrolmanWyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA. grolman@fas.harvard.edu.
Pin-Jou WuCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ponnie.wu@gmail.com.
Owen S FentonDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. osfenton@mit.edu.
Lang H LeeCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. lhlee@bwh.harvard.edu.
Mark W TibbittDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. mtibbitt@ethz.ch.
Jason L AndresenDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. jandrese@mit.edu.
Jennifer R WenCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. jwen4@bwh.harvard.edu.
Anna H HaCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ahha@bwh.harvard.edu.
Fabrizio BuffoloCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. fbuffolo@bwh.harvard.edu.
Alain van MilExperimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands. a.vanmil@umcutrecht.nl.
Carlijn V C BoutenDepartment of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, the Netherlands. c.v.c.bouten@tue.nl.ORCID 0000-0003-1035-5094
Simon C BodyCenter for Perioperative Genomics, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. sbody@bwh.harvard.edu.
David J MooneyWyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA. mooneyd@seas.harvard.edu.
Joost P G SluijterExperimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands. j.sluijter@umcutrecht.nl.ORCID 0000-0003-2088-9102
Masanori AikawaCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. maikawa@bwh.harvard.edu.
Jesper HjortnaesExperimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands. jhjortna@umcutrecht.nl.
Robert LangerDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. rlanger@mit.edu.
Elena AikawaCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. eaikawa@bwh.harvard.edu.
Brigham and Women's Hospital · USHarvard University · USMassachusetts Institute of Technology · USUtrecht University · NLEindhoven University of Technology · NLETH Zurich · CH

Funding

Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2M
Improving Mitral Compensation In Ischemic RegurgitationR01HL141917 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2018 to 2021
$5.6M
Macrophage-derived microcalcificaitonsR01HL136431 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2017 to 2020
$2.7M
Genetic Etiology of Bicuspid Aortic Valve DiseaseR01HL114823 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI BODY, SIMON C · 2012 to 2016
$2.1M
Aortic valve microcalcificationR01HL114805 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2012 to 2016
$2.1M
NCATS NIH HHS UL1 TR001102NHLBI NIH HHS R01 HL114805NHLBI NIH HHS R01 HL114823NHLBI NIH HHS R01 HL136431NHLBI NIH HHS R01 HL141917
6 · The paper itself

Abstract

In calcific aortic valve disease (CAVD), microcalcifications originating from nanoscale calcifying vesicles disrupt the aortic valve (AV) leaflets, which consist of three (biomechanically) distinct layers: the fibrosa, spongiosa, and ventricularis. CAVD has no pharmacotherapy and lacks in vitro models as a result of complex valvular biomechanical features surrounding resident mechanosensitive valvular interstitial cells (VICs). We measured layer-specific mechanical properties of the human AV and engineered a three-dimensional (3D)-bioprinted CAVD model that recapitulates leaflet layer biomechanics for the first time. Human AV leaflet layers were separated by microdissection, and nanoindentation determined layer-specific Young’s moduli. Methacrylated gelatin (GelMA)/methacrylated hyaluronic acid (HAMA) hydrogels were tuned to duplicate layer-specific mechanical characteristics, followed by 3D-printing with encapsulated human VICs. Hydrogels were exposed to osteogenic media (OM) to induce microcalcification, and VIC pathogenesis was assessed by near infrared or immunofluorescence microscopy. Median Young’s moduli of the AV layers were 37.1, 15.4, and 26.9 kPa (fibrosa/spongiosa/ventricularis, respectively). The fibrosa and spongiosa Young’s moduli matched the 3D 5% GelMa/1% HAMA UV-crosslinked hydrogels. OM stimulation of VIC-laden bioprinted hydrogels induced microcalcification without apoptosis. We report the first layer-specific measurements of human AV moduli and a novel 3D-bioprinted CAVD model that potentiates microcalcification by mimicking the native AV mechanical environment. This work sheds light on valvular mechanobiology and could facilitate high-throughput drug-screening in CAVD.

Indexed as

3D printingaortic valvebioprintingcalcific aortic valve diseasecalcificationmechanobiologymicrodissectionnanoindentation

Identifiers

PMID29751516
PMCPMC5977310
OpenAlexW2801657424

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.