Tβ4-Engineered ADSC Extracellular Vesicles Rescue Cell Senescence Through Separable Microneedle Patches for Diabetic Wound Healing.

Ding Y, Wang J, Li J, Cheng Y, Zhou S, Zhang Y, Zhao Y, Zhou M

Advanced science (Weinheim, Baden-Wurttemberg, Germany)25 Apr 2025Cited by 23 (Europe PMC)

PMID40279568PMCIDPMC12245110DOI10.1002/advs.202505009PepBankPUB-40279568

Summary

Microneedles loaded with bioactive substances have demonstrated efficacy in wound healing, while their application in the elderly chronic wounds, aggravated by cellular senescence, is still a significant challenge. Here, a novel therapeutic strategy is presented utilizing Thymosin β4 (Tβ4)-modified adipose-derived stem cell extracellular vesicles (ADSC-EVs) delivered via separable microneedle patches (MN@EVs^Tβ4). The therapeutic EVs^Tβ4 are derived from ADSCs that overexpress Tβ4, a factor that reverses cellular senescence. Leveraging the drug-loading and release properties of gelatin methacryloyl and poly(ethylene glycol) diacrylate, EVs^Tβ4 are encapsulated within the tips of the microneedles. Notably, the soluble hyaluronic acid base layer dissolves rapidly and separates from the tips upon exudate absorption, enabling a sustained release of EVs^Tβ4. Subsequently, it is demonstrated its ability to mitigate senescence and improve function via the PTEN/PI3K/AKT pathway. Furthermore, MN@EVs^Tβ4 patches showed significant efficacy in reversing senescence and promoting wound healing in diabetic wound models. Thus, the engineered ADSC-EVs, combined with separable microneedle patches, represent a promising bioengineering strategy for clinical wound management.

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

Results from this study4

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

Studies that did not test the peptide alone4

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 diabetic wound models, MN@EVsTβ4 microneedle patches showed significant efficacy in reversing senescence.
In plain wordsIn diabetic wound models, microneedle patches with engineered vesicles reversed cell aging signs.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseSenescence reversal in diabetic wound models
Study
n: not reported in source
Outcome group
Aging markers · Skin and wound
Source sentences
Summary
Furthermore, MN@EVs^Tβ4 patches showed significant efficacy in reversing senescence and promoting wound healing in diabetic wound models.
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-4027956803
02AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In diabetic wound models, MN@EVsTβ4 microneedle patches showed significant efficacy in promoting wound healing.
In plain wordsIn diabetic wound models, microneedle patches with engineered vesicles promoted wound healing.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseDiabetic wound healing
Study
n: not reported in source
Outcome group
Wound healing · Skin and wound
Source sentences
Summary
Furthermore, MN@EVs^Tβ4 patches showed significant efficacy in reversing senescence and promoting wound healing in diabetic wound models.
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-4027956804
03LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Efficacy outcome
Tβ4-engineered ADSC extracellular vesicles mitigated senescence and improved function.
In plain wordsVesicles from stem cells engineered to make thymosin beta‑4 reduced cell aging signs.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseCellular senescence
Study
n: not reported in source
Outcome group
Aging markers · Skin and wound
Source sentences
Summary
Subsequently, it is demonstrated its ability to mitigate senescence and improve function via the PTEN/PI3K/AKT pathway.
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-4027956801
04LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
Tβ4-engineered ADSC extracellular vesicles acted via the PTEN/PI3K/AKT pathway.
In plain wordsVesicles from stem cells engineered to make thymosin beta‑4 acted through the PTEN/PI3K/AKT pathway.
Peptide
Thymosin beta-4 (human)
Outcome
Not applicablePTEN/PI3K/AKT pathway
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Skin and wound
Source sentences
Summary
Subsequently, it is demonstrated its ability to mitigate senescence and improve function via the PTEN/PI3K/AKT pathway.
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-4027956802

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

Subjects

Terms as the source lists them.

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