Evidence map›Paper›PMID 40837579›Full record

ArticleAdvanced functional materials2025

Bioorthogonal Engineering of Cellular Microenvironments Using Isonitrile Ligations.

Ping Zhou, Lauren Brown, Christopher M Madl

Abstract read
In one paragraph

Article in Advanced functional materials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

3 authors.

Ping ZhouDepartment of Materials Science & Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lauren BrownDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Christopher M MadlDepartment of Materials Science & Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

Funding

Elucidating Effects of Fibrosis on Aged Stem Cells with Dynamic BiomaterialsR00AG071738 · NIA · UNIVERSITY OF PENNSYLVANIA · PI MADL, CHRISTOPHER MATTHEW · 2023 to 2025
$742k
NIA NIH HHS R00 AG071738
6 · The paper itself

Abstract

Hydrogels are routinely used as scaffolds to mimic the extracellular matrix for tissue engineering. However, common strategies to covalently crosslink hydrogels employ reaction conditions with potential off-target biological reactivity. The limited number of suitable bioorthogonal chemistries for hydrogel crosslinking restricts how many material properties can be independently addressed to control cell fate. To expand the bioorthogonal toolkit available for hydrogel crosslinking, we identify isonitrile ligations as a promising class of reactions. Isonitriles are compact, stable, selective, and biocompatible moieties that react with chlorooxime (ChO), tetrazine (Tz), and azomethine imine (AMI) functional groups under physiological conditions. We demonstrate that all three ligation reactions can form hydrogels, with isonitrile-ChO ligation exhibiting optimal gelation properties. Synthetic poly(ethylene glycol) (PEG) hydrogels crosslinked by isonitrile-ChO ligation exhibit rapid gelation kinetics, elastic mechanical properties, stability under physiological conditions, and high biocompatibility. By combining ChO-functionalized multi-arm PEGs with isonitrile-functionalized engineered elastin-like proteins (ELPs), we demonstrate simultaneous control over network connectivity and adhesive ligand presentation, which in turn regulate cell spreading. These hydrogels enable the long-term culture of numerous human cell types relevant to regenerative medicine. Furthermore, we demonstrate that isonitrile-ChO ligation is orthogonal to common azide-alkyne cycloaddition, enabling independent, bioorthogonal functionalization of hydrogels containing live cells.

Indexed as

bioorthogonal chemistryengineered extracellular matriceshydrogelsisonitrile ligationrecombinant protein materials

Identifiers

PMID40837579
PMCPMC12360401

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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.