Evidence map›Paper›PMID 39122702›Full record

ArticleNature communications2024

Hydrogel crosslinking modulates macrophages, fibroblasts, and their communication, during wound healing.

Sergei Butenko, Raji R Nagalla, Christian F Guerrero-Juarez, Francesco Palomba, Li-Mor David, Ronald Q Nguyen, Denise Gay, Axel A Almet, Michelle A Digman, Qing Nie and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
–field-weighted citation impact
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

79 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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  5. Smart Bioinks for 4D Bioprinting: Requirements, Design, and Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
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  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Polysaccharide-Based Encapsulation of Microbes for Enhanced Microbial Therapy.Polymer science & technology (Washington, D.C.) · 2026
    Review
  16. Review
  17. Article
  18. Article
  19. Macrophage-Fibroblast Crosstalk Shapes Wound Repair Signaling In Vitro.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  20. Article

19 more citing papers are in PubMed but not listed here.

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.

Sergei Butenko *Department of Biomedical Engineering, University of California Irvine, Irvine, CA, USA.ORCID 0000-0001-9759-9897
Raji R Nagalla *Department of Biomedical Engineering, University of California Irvine, Irvine, CA, USA.
Christian F Guerrero-JuarezCarle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL, USA.ORCID 0000-0002-6245-6412
Francesco PalombaDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA.
Li-Mor DavidDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA.
Ronald Q NguyenDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA.ORCID 0009-0003-1715-2852
Denise GayDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0001-7340-8427
Axel A AlmetNSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA, USA.
Michelle A DigmanDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA.ORCID 0000-0003-4611-7100
Qing NieNSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA, USA.
Philip O ScumpiaDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-2563-2042
Maksim V PlikusDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0002-8845-2559
Wendy F LiuDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA. wendy.liu@uci.edu.ORCID 0000-0002-8904-7643

Funding

UCI P30 Skin Center Systems Biology CoreP30AR075047 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI ANDERSEN, BOGI, GANESAN, ANAND K · 2019 to 2025
$5.1M
Multiscale Models of Wound Cell Plasticity for RegenerationU01AR073159 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAI, XING, NIE, QING · 2018 to 2022
$3.5M
Biophysical regulation of macrophage functionR01AI151301 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIU, WENDY · 2020 to 2024
$2.9M
Tissue Size and Precision Control in Growing Hair FolliclesR01AR079150 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Qing Nie, Maksim V Plikus · 2022 to 2026
$2.7M
Leveraging immune-fibroblast interactions for biomaterial induced skin regenerationR01AR079470 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SCUMPIA, PHILIP · 2021 to 2025
$2.6M
Multiphoton Microscope for Cardiovascular and Tissue EngineeringS10OD025064 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI BOTVINICK, ELLIOT LAWRENCE · 2019 to 2019
$595k
Mechanical regulation of skin repair and regenerationR21AR077288 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIU, WENDY · 2020 to 2021
$375k
NIAID NIH HHS R01 AI151301NIAMS NIH HHS P30 AR075047NIAMS NIH HHS R01 AR079150NIAMS NIH HHS R01 AR079470NIAMS NIH HHS R21 AR077288NIAMS NIH HHS U01 AR073159NIH HHS S10 OD025064NSF | Directorate for Mathematical & Physical Sciences | Division of Mathematical Sciences (DMS) DMS1763272Simons Foundation 594598U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) 1R01AI151301U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 1R21AR077288U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) P30AR075047U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01AR079150U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01AR079470U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) U01AR073159U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD) S10OD025064
6 · The paper itself

Abstract

Biomaterial wound dressings, such as hydrogels, interact with host cells to regulate tissue repair. This study investigates how crosslinking of gelatin-based hydrogels influences immune and stromal cell behavior and wound healing in female mice. We observe that softer, lightly crosslinked hydrogels promote greater cellular infiltration and result in smaller scars compared to stiffer, heavily crosslinked hydrogels. Using single-cell RNA sequencing, we further show that heavily crosslinked hydrogels increase inflammation and lead to the formation of a distinct macrophage subpopulation exhibiting signs of oxidative activity and cell fusion. Conversely, lightly crosslinked hydrogels are more readily taken up by macrophages and integrated within the tissue. The physical properties differentially affect macrophage and fibroblast interactions, with heavily crosslinked hydrogels promoting pro-fibrotic fibroblast activity that drives macrophage fusion through RANKL signaling. These findings suggest that tuning the physical properties of hydrogels can guide cellular responses and improve healing, offering insights for designing better biomaterials for wound treatment.

Indexed as

FibroblastsHydrogelsMacrophagesWound HealingAnimalsBiocompatible MaterialsCell CommunicationCross-Linking ReagentsFemaleGelatinInflammationMiceMice, Inbred C57BLRANK LigandBiocompatible MaterialsCross-Linking ReagentsGelatinHydrogelsRANK LigandTnfsf11 protein, mouse

Identifiers

PMID39122702
PMCPMC11315930

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Registered trials

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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.