Evidence map›Paper›PMID 31776019›Full record

ArticleBiomaterials2020

Cell-mediated matrix stiffening accompanies capillary morphogenesis in ultra-soft amorphous hydrogels.

Benjamin A Juliar, Jeffrey A Beamish, Megan E Busch, David S Cleveland, Likitha Nimmagadda, Andrew J Putnam

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.7field-weighted citation impact, top 18% 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

26 citing papers in PubMed, 37 citations in OpenAlex.

  1. Ultrasound-responsive composite hydrogels: Design rules for spatiotemporally controlled drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. A Tissue Engineering's Guide to Biomimicry.Macromolecular bioscience · 2025
    Review
  7. Article
  8. Biofabrication and Characterization of Vascularizing PEG-Norbornene Microgels.Journal of biomedical materials research. Part A · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. The extracellular matrix mechanics in the vasculature.Nature cardiovascular research · 2023
    Review
  17. 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

6 authors at 1 institution in 1 country.

Benjamin A JuliarDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Jeffrey A BeamishDivision of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Megan E BuschDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
David S ClevelandDivision of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Likitha NimmagaddaDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Andrew J PutnamDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. Electronic address: putnam@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Tissue Engineering and RegenerationT32DE007057 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID H. KOHN · 1985 to 2026
$17.3M
RESEARCH TRAINING IN NEPHROLOGYT32DK007378 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PENNATHUR, SUBRAMANIAM · 1986 to 2019
$5.9M
Regulation and Enhancement of Angiogenesis in Dense Fibrin MatricesR01HL085339 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTNAM, ANDREW J · 2007 to 2024
$5.4M
Training Program in Translational Cardiovascular Research and EntrepreneurshipT32HL125242 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MICHELE, DANIEL E · 2015 to 2024
$1.9M
NHLBI NIH HHS R01 HL085339NHLBI NIH HHS T32 HL125242NIDCR NIH HHS T32 DE007057NIDDK NIH HHS T32 DK007378
6 · The paper itself

Abstract

There is a critical need for biomaterials that support robust neovascularization for a wide-range of clinical applications. Here we report how cells alter tissue-level mechanical properties during capillary morphogenesis using a model of endothelial-stromal cell co-culture within poly(ethylene glycol) (PEG) based hydrogels. After a week of culture, we observed substantial stiffening in hydrogels with very soft initial properties. Endothelial cells or stromal cells alone, however, failed to induce hydrogel stiffening. This stiffening tightly correlated with degree of vessel formation but not with hydrogel compaction or cellular proliferation. Despite a lack of fibrillar architecture within the PEG hydrogels, cell-generated contractile forces were essential for hydrogel stiffening. Upregulation of alpha smooth muscle actin and collagen-1 was also correlated with enhanced vessel formation and hydrogel stiffening. Blocking cell-mediated hydrogel degradation abolished stiffening, demonstrating that matrix metalloproteinase (MMP)-mediated remodeling is required for stiffening to occur. These results highlight the dynamic reciprocity between cells and their mechanical microenvironment during capillary morphogenesis and provide important insights for the rational design of materials for vasculogenic applications.

Indexed as

Endothelial CellsHydrogelsBiocompatible MaterialsMorphogenesisPolyethylene GlycolsBiocompatible MaterialsHydrogelsPolyethylene GlycolsCapillary morphogenesisHydrogelMatrix metalloproteinaseMechanical propertiespoly(ethylene glycol)

Identifiers

PMID31776019
PMCPMC6930336
OpenAlexW2988139506

What OpenQuestion holds

Textmetadata
LicenceTDM
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.