Evidence map›Paper›PMID 40554673›Full record

ArticleBiomacromolecules2025

Reinforcement of Fibrillar Collagen Hydrogels with Bioorthogonal Covalent Crosslinks.

Lucia G Brunel, Chris M Long, Fotis Christakopoulos, Betty Cai, Narelli de Paiva Narciso, Patrik K Johansson, Diya Singhal, Neil J Baugh, Daiyao Zhang, Annika Enejder and 2 more

Abstract read
In one paragraph

Article in Biomacromolecules, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Lucia G BrunelDepartment of Chemical Engineering, Stanford University, Stanford, California 94305, United States.ORCID 0000-0003-0327-5635
Chris M LongDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.
Fotis ChristakopoulosDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.ORCID 0000-0001-7383-5875
Betty CaiDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.
Narelli de Paiva NarcisoDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.
Patrik K JohanssonDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.
Diya SinghalDepartment of Chemical Engineering, Stanford University, Stanford, California 94305, United States.
Neil J BaughDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.
Daiyao ZhangDepartment of Chemical Engineering, Stanford University, Stanford, California 94305, United States.
Annika EnejderDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.ORCID 0000-0003-2000-1353
David MyungDepartment of Chemical Engineering, Stanford University, Stanford, California 94305, United States.
Sarah C HeilshornDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.ORCID 0000-0002-9801-6304

Funding

Stanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI Jeffrey L Goldberg · 2017 to 2026
$8.0M
Corneal Scar Repair through SPAACKL: Sutureless, Pro-regenerative Anterior Additive Collagen gel KeratopLastyR01EY033363 · NEI · STANFORD UNIVERSITY · PI David Myung · 2022 to 2026
$2.5M
3D bioprinting of a bilayered, tissue engineered corneaR01EY035697 · NEI · STANFORD UNIVERSITY · PI Sarah C Heilshorn, David Myung · 2024 to 2026
$1.6M
Liposome-crosslinked hyaluronic acid hydrogels with localized protein delivery for myocardial infarction therapyF31HL175888 · NHLBI · STANFORD UNIVERSITY · PI Neil Baugh · 2024 to 2026
$130k
3D bioprinting of regenerative, corneal cell-laden inks to treat corneal blindnessF31EY034785 · NEI · STANFORD UNIVERSITY · PI BRUNEL, LUCIA · 2023 to 2024
$82k
NEI NIH HHS F31 EY034785NEI NIH HHS P30 EY026877NEI NIH HHS R01 EY033363NEI NIH HHS R01 EY035697NHLBI NIH HHS F31 HL175888
6 · The paper itself

Abstract

Bioorthogonal covalent crosslinking stabilizes collagen type I hydrogels, improving their structural integrity for tissue engineering applications with encapsulated living cells. The chemical modification required for crosslinking, however, interferes with the fibrillar nature of the collagen, leading instead to an amorphous network without fibers. We demonstrate an approach to perform bioconjugation chemistry on collagen with controlled localization such that the modified collagen retains its ability to self-assemble into a fibrillar network while also displaying functional groups for covalent crosslinking with bioorthogonal click chemistry. The collagen matrix is formed through a sequential crosslinking process, in which the modified collagen first physically assembles into fibers and then is covalently crosslinked. This approach preserves the fibrous architecture of the collagen, guiding the behavior of encapsulated human corneal mesenchymal stromal cells while also reinforcing fibers through covalent crosslinks, strengthening the stability of the cell-laden collagen hydrogel against cell-induced contraction and enzymatic degradation.

Indexed as

Collagen Type ICross-Linking ReagentsHydrogelsClick ChemistryCorneaHumansMesenchymal Stem CellsTissue EngineeringCollagen Type ICross-Linking ReagentsHydrogels

Identifiers

PMID40554673
PMCPMC12715433

What OpenQuestion holds

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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.