Decidualization-empowered ECM hydrogel integrating sustained Tβ4 release drives endometrial regeneration in intrauterine adhesions.

Liang Y, Yu Z, Du S, Guo Y, Li J, Yan Y, Jin S, Liang W, Li M, Jin N, Yang J, Peng Z and 6 more

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Chen Z, Yang H, Liu Z, Shuai Q, Li L, Xie J

Nature communications21 Jan 2026Cited by 3 (Europe PMC)

PMID41565687PMCIDPMC12923885DOI10.1038/s41467-026-68677-wPepBankPUB-41565687

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Summary

Intrauterine adhesions (IUA), a leading cause of female infertility, result from a pathological switch in the uterine injury response from regeneration to fibrotic scarring. Current treatments are often inadequate as they fail to address this fundamental shift. Here, we report a "decidualization-empowered" hydrogel that reverses this pathology by synergistically combining a bioactive extracellular matrix from decidualized endometrium (DEndo-UdECM) with the sustained release of the anti-fibrotic peptide Thymosin β4 (Tβ4). In a murine IUA model, a single administration of the hydrogel restores endometrial architecture, resolves fibrosis, and, most critically, leads to a near-complete recovery of fertility. Mechanistically, the hydrogel orchestrates a pro-regenerative niche by reprogramming macrophages to an M2 phenotype while dually inhibiting pyroptosis-driven inflammation and the canonical TGF-β/Smad3 fibrotic cascade. Together, these findings demonstrate that mimicking the biological intelligence of a physiological niche can resolve complex fibrotic diseases and restore organ function.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone6

In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin beta-4 (human).

01AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In mice with intrauterine adhesions, a single dose of a decidualized ECM hydrogel with sustained Tβ4 release restored endometrial architecture.
In plain wordsIn mice with uterine scarring, a single hydrogel containing thymosin β4 and uterine matrix restored the uterine lining structure.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseEndometrial architecture
Study
mousen: not reported in source
Intrauterine adhesion (IUA) model
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Source sentences
Summary
In a murine IUA model, a single administration of the hydrogel restores endometrial architecture
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we report a "decidualization-empowered" hydrogel that reverses this pathology by synergistically combining a bioactive extracellular matrix from decidualized endometrium (DEndo-UdECM) with the sustained release of the anti-fibrotic peptide Thymosin β4 (Tβ4).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-4156568701
02AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In mice with intrauterine adhesions, a single dose of a decidualized ECM hydrogel with sustained Tβ4 release resolved fibrosis.
In plain wordsIn mice with uterine scarring, a single hydrogel containing thymosin β4 and uterine matrix resolved the scarring.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseFibrosis
Study
mousen: not reported in source
Intrauterine adhesion (IUA) model
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Source sentences
Summary
In a murine IUA model, a single administration of the hydrogel restores endometrial architecture, resolves fibrosis
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we report a "decidualization-empowered" hydrogel that reverses this pathology by synergistically combining a bioactive extracellular matrix from decidualized endometrium (DEndo-UdECM) with the sustained release of the anti-fibrotic peptide Thymosin β4 (Tβ4).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-4156568702
03AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In mice with intrauterine adhesions, a single dose of a decidualized ECM hydrogel with sustained Tβ4 release led to a near-complete recovery of fertility.
In plain wordsIn mice with uterine scarring, a single hydrogel containing thymosin β4 and uterine matrix led to near-complete recovery of fertility.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseFertility recovery
Study
mousen: not reported in source
Intrauterine adhesion (IUA) model
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Source sentences
Summary
In a murine IUA model, a single administration of the hydrogel restores endometrial architecture, resolves fibrosis, and, most critically, leads to a near-complete recovery of fertility
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we report a "decidualization-empowered" hydrogel that reverses this pathology by synergistically combining a bioactive extracellular matrix from decidualized endometrium (DEndo-UdECM) with the sustained release of the anti-fibrotic peptide Thymosin β4 (Tβ4).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-4156568703
04AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In mice with intrauterine adhesions, the Tβ4-releasing decidualized ECM hydrogel reprogrammed macrophages to an M2 phenotype.
In plain wordsIn mice with uterine scarring, the hydrogel containing thymosin β4 shifted macrophages toward a repair-supporting M2 type.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseMacrophage M2 polarization
Study
mousen: not reported in source
Intrauterine adhesion (IUA) model
Outcome group
Immune response · Immune and inflammation
Source sentences
Summary
Mechanistically, the hydrogel orchestrates a pro-regenerative niche by reprogramming macrophages to an M2 phenotype
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we report a "decidualization-empowered" hydrogel that reverses this pathology by synergistically combining a bioactive extracellular matrix from decidualized endometrium (DEndo-UdECM) with the sustained release of the anti-fibrotic peptide Thymosin β4 (Tβ4).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-4156568704
05AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In mice with intrauterine adhesions, the Tβ4-releasing decidualized ECM hydrogel inhibited pyroptosis-driven inflammation.
In plain wordsIn mice with uterine scarring, the hydrogel containing thymosin β4 reduced a form of inflammatory cell death.
Peptide
Thymosin beta-4 (human)
Outcome
DecreasePyroptosis-driven inflammation
Study
mousen: not reported in source
Intrauterine adhesion (IUA) model
Outcome group
Inflammation markers · Immune and inflammation
Source sentences
Summary
while dually inhibiting pyroptosis-driven inflammation and the canonical TGF-β/Smad3 fibrotic cascade.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we report a "decidualization-empowered" hydrogel that reverses this pathology by synergistically combining a bioactive extracellular matrix from decidualized endometrium (DEndo-UdECM) with the sustained release of the anti-fibrotic peptide Thymosin β4 (Tβ4).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-4156568705
06AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In mice with intrauterine adhesions, the Tβ4-releasing decidualized ECM hydrogel inhibited the canonical TGF-β/Smad3 fibrotic cascade.
In plain wordsIn mice with uterine scarring, the hydrogel containing thymosin β4 blocked a signalling pathway that drives scarring.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseTGF-β/Smad3 fibrotic cascade
Study
mousen: not reported in source
Intrauterine adhesion (IUA) model
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Source sentences
Summary
the canonical TGF-β/Smad3 fibrotic cascade.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we report a "decidualization-empowered" hydrogel that reverses this pathology by synergistically combining a bioactive extracellular matrix from decidualized endometrium (DEndo-UdECM) with the sustained release of the anti-fibrotic peptide Thymosin β4 (Tβ4).
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-4156568706

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 01:52 UTC
Study results updated
Version 1
12 Oct 2026, 18:17 UTC
First added · source update from Europe PMC

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