Evidence map›Paper›PMID 41981572›Full record

ArticleJournal of nanobiotechnology2026

Decellularized extracellular matrix hydrogel-mediated EVs therapy alleviates diabetic erectile dysfunction by targeting the miR-203a-3p/TMEM33 Axis.

Hao Liu, Zhenjie Zang, Danfeng Zhao, Jing Zhang, Zhenqing Wang, Qiang Fu, Keqin Zhang

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2026. 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

7 authors.

Hao Liu *Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
Zhenjie Zang *Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
Danfeng ZhaoDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
Jing ZhangRenowned Specialist Clinic, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
Zhenqing WangDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China. wangzq1412@163.com.
Qiang FuDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China. qiangfu68@126.com.
Keqin ZhangDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China. kqzhang81@aliyun.com.

Funding

National Natural Science Foundation of China No.82471653Natural Science Foundation of Shandong Province ZR2021MH101
6 · The paper itself

Abstract

Diabetic erectile dysfunction (DMED) is a common complication among male patients with diabetes. Therapies primarily based on phosphodiesterase type 5 inhibitors (PDE5Is) often yield suboptimal results. Extracellular vesicles (EVs) have emerged as a promising therapeutic strategy; however, their clinical translation is hindered by rapid in vivo clearance and limited inherent bioactivity. Therefore, we developed an innovative combined therapeutic approach. First, we fabricated an injectable, thermosensitive hydrogel (ECMTA-Hydrogel) by combining a decellularized porcine corpus cavernosum extracellular matrix (ECM) with tannic acid, which exhibits excellent biocompatibility and rapid gelation at body temperature (37 °C), enabling prolonged local retention of EVs within the corpus cavernosum. Second, we pretreated mesenchymal stem cells (MSCs) with pioglitazone to generate engineered EVs (PGZ-EVs) with enhanced bioactivity. Experiments confirmed that the ECMTA-Hydrogel facilitates sustained release of PGZ-EVs, extending their duration of action. In a DMED rat model, the combined ECMTA-PGZ-EVs therapy demonstrated superior efficacy, markedly improving erectile function and effectively reversing pathological phenotypic switching and apoptosis in corpus cavernosum smooth muscle cells (CCSMCs). Mechanistically, we identified that miR-203a-3p, highly enriched in PGZ-EVs, directly targets and suppresses the endoplasmic reticulum transmembrane protein TMEM33, thereby mitigating diabetes-induced endoplasmic reticulum stress (ERS). This pathway represents the key mechanism underlying the cytoprotective effects of PGZ-EVs. In summary, this study not only establishes an efficient natural matrix hydrogel-based delivery system but also augments the therapeutic potential of EVs via engineered modification. Furthermore, we elucidate a novel mechanism involving the miR-203a-3p/TMEM33/ERS axis, offering a promising therapeutic strategy for the clinical management of DMED.

Indexed as

Diabetes ComplicationsErectile DysfunctionExtracellular MatrixExtracellular VesiclesHydrogelsMembrane ProteinsMicroRNAsAnimalsDiabetes Mellitus, ExperimentalMaleMesenchymal Stem CellsRatsRats, Sprague-DawleySwineHydrogelsMembrane ProteinsMicroRNAsDecellularized Extracellular Matrix HydrogelDiabetes mellitusErectile dysfunctionExtracellular vesiclesPioglitazone

Identifiers

PMID41981572
PMCPMC13200310

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 Socratic graph.