Evidence map›Paper›PMID 28371736›Full record

ArticleBiomaterials2017

On-demand dissolution of modular, synthetic extracellular matrix reveals local epithelial-stromal communication networks.

Jorge Valdez, Christi D Cook, Caroline Chopko Ahrens, Alex J Wang, Alexander Brown, Manu Kumar, Linda Stockdale, Daniel Rothenberg, Kasper Renggli, Elizabeth Gordon and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Biomaterials, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

56 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Enzymatic Methods for Assembling and Modifying Hydrogel Biomaterials.Regenerative engineering and translational medicine · 2025
    Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Engineered hydrogels for mechanobiology.Nature reviews. Methods primers · 2022
    Article
  19. Article
  20. Bioengineering Approaches to Improve Gynecological Cancer Outcomes.Current opinion in biomedical engineering · 2022
    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

13 authors at 1 institution in 1 country.

Jorge ValdezDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Christi D CookDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Caroline Chopko AhrensDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Alex J WangDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Alexander BrownDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Manu KumarDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Linda StockdaleDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Daniel RothenbergDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kasper RenggliDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Elizabeth GordonDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Douglas LauffenburgerDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Forest WhiteDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Linda GriffithDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: griff@mit.edu.
Massachusetts Institute of Technology · US

Funding

Interdepartmental Biotechnology Training ProgramT32GM008334 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WITTRUP, KARL DANE · 1989 to 2018
$15.2M
Perfused 3D Tissue Surrogates for Complex Cell-Cell Communication SystemsR01EB010246 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GRIFFITH, LINDA G · 2009 to 2013
$3.3M
All-Human Microphysical Model of Metastasis TherapyUH2TR000496 · NCATS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GRIFFITH, LINDA G · 2012 to 2013
$2.3M
NCATS NIH HHS UH2 TR000496NIBIB NIH HHS R01 EB010246NIGMS NIH HHS T32 GM008334
6 · The paper itself

Abstract

Methods to parse paracrine epithelial-stromal communication networks are a vital need in drug development, as disruption of these networks underlies diseases ranging from cancer to endometriosis. Here, we describe a modular, synthetic, and dissolvable extracellular matrix (MSD-ECM) hydrogel that fosters functional 3D epithelial-stromal co-culture, and that can be dissolved on-demand to recover cells and paracrine signaling proteins intact for subsequent analysis. Specifically, synthetic polymer hydrogels, modified with cell-interacting adhesion motifs and crosslinked with peptides that include a substrate for cell-mediated proteolytic remodeling, can be rapidly dissolved by an engineered version of the microbial transpeptidase Sortase A (SrtA) if the crosslinking peptide includes a SrtA substrate motif and a soluble second substrate. SrtA-mediated dissolution affected only 1 of 31 cytokines and growth factors assayed, whereas standard protease degradation methods destroyed about half of these same molecules. Using co-encapsulated endometrial epithelial and stromal cells as one model system, we show that the dynamic cytokine and growth factor response of co-cultures to an inflammatory cue is richer and more nuanced when measured from SrtA-dissolved gel microenvironments than from the culture supernate. This system employs accessible, reproducible reagents and facile protocols; hence, has potential as a tool in identifying and validating therapeutic targets in complex diseases.

Indexed as

Amino Acid SequenceAminoacyltransferasesBacterial ProteinsCell CommunicationCell Line, TumorCoculture TechniquesCysteine EndopeptidasesEpithelial CellsExtracellular MatrixHumansHydrogel, Polyethylene Glycol DimethacrylateInflammation MediatorsIntercellular Signaling Peptides and ProteinsInterleukin-1betaKineticsPeptidesAminoacyltransferasesBacterial ProteinsCysteine EndopeptidasesHydrogel, Polyethylene Glycol DimethacrylateInflammation MediatorsIntercellular Signaling Peptides and ProteinsInterleukin-1betaPeptidessortase ABiomaterialsMatrixSignalingSortaseSystems biology

Identifiers

PMID28371736
PMCPMC5461961
OpenAlexW2601936925

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.