Evidence map›Paper›PMID 41088427›Full record

ArticleStem cell research & therapy2025

ROS-responsive 3D biological scaffold delivers hypoxia-primed extracellular vesicles for targeted modulation of neuroinflammation in intracerebral hemorrhage.

Aobo Zhang, Dan Qiao, Ziyang Jia, Zhanzhan Zhang, Dongdong Yan, Chengrui Nan, Liqiang Liu, Yunpeng Shi

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Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Aobo ZhangDepartment of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, 100070, China. zab199915@163.com.
Dan QiaoDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Ziyang JiaDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Zhanzhan ZhangDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Dongdong YanDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Chengrui NanDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Liqiang LiuDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Yunpeng ShiDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. syyppp@hebmu.edu.cn.

Funding

Central Guiding Local Science and Technology Development Fund Projects 236Z7752GSpecial Project for the Construction of Hebei Province International Science and Technology Cooperation Base 193977143Dsupported by Hebei Natural Science Foundation H2021206027the Medical Research Project of Hebei Provincial Health Commission 20230031
6 · The paper itself

Abstract

backgroundEmerging evidence suggests that paracrine mechanisms may underlie the therapeutic effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles (EVs) (hUCMSC-exos) in mitigating neuroinflammation following intracerebral hemorrhage (ICH). Hypoxic preconditioning enhances the paracrine efficacy of hUCMSC-exos. Building on prior studies [1, 2], we developed a ROS-responsive three-dimensional (3D) biological scaffold encapsulating hypoxia-primed EVs (Hypo-Exos) for sustained release under reactive oxygen species (ROS)-rich conditions.

methodsThe 3D biological scaffold was fabricated via a thermoresponsive crosslinking strategy using gelatin methacrylate (GelMA), silk fibroin, and brain-derived decellularized extracellular matrix (dECM), functionalized with phenylboronic acid (PBA)-modified polyvinyl alcohol (PVA). Hypo-Exos, enriched with miR-146b via hypoxia-inducible factor-1α (HIF-1α) activation, were incorporated into the scaffold using advanced 3D bioprinting. Dual-luciferase reporter assays validated miR-146b targeting of the 3'UTR of COP1 (an E3 ubiquitin ligase). In a rat ICH model, the scaffold was implanted in situ. Neurological function, angiogenesis, neuroinflammation, and synaptic plasticity were evaluated at days 1, 4, 7, and 14.

resultsThe 3D biological scaffold enabled sustained delivery of Hypo-Exos, shifting microglial polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes, thereby attenuating neuroinflammation and neuronal damage. Mechanistically, miR-146b suppressed COP1 expression via post-transcriptional silencing, thereby attenuating NF-κB p65 signaling and downregulating pro-inflammatory cytokines.

conclusionThe ROS-responsive 3D biological scaffold -mediated delivery of Hypo-Exos modulates neuroinflammation through ubiquitination pathways, stabilizes the early-phase ICH microenvironment, and improves functional recovery. This platform represents a promising therapeutic strategy for ICH, offering dual advantages as a drug delivery system and a regenerative therapy.

Indexed as

Cerebral HemorrhageExtracellular VesiclesNeuroinflammatory DiseasesReactive Oxygen SpeciesTissue ScaffoldsAnimalsHumansMaleMesenchymal Stem CellsMicroRNAsRatsRats, Sprague-DawleyMicroRNAsReactive Oxygen Species3D biological scaffoldHypo-ExosIntracerebral hemorrhagemiR-146b/COP1Neuroinflammation

Identifiers

PMID41088427
PMCPMC12522757

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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.