I. Research Overview
This study composites CCL22loaded PLGA microparticles with various hydrogels for local delivery to the ischemic heart to recruit regulatory T cells (Tregs) and attenuate cardiac injury in severe ischemia models.

II. Core Innovative Breakthroughs
Instead of broadspectrum immune suppression, chemokines are adopted to locally enrich Tregs. The delivery and retention performance of thermosensitive, injectable and tissue adhesive hydrogels are systematically compared. It is found that therapeutic efficacy correlates with the severity of ischemic injury, with more definite benefits observed in severe ischemia models.

III. Key Material Design and Validation
CCL22loaded microparticles are suspended in hydrogels, and tissueadhesive hydrogels are screened for invivo application. Sustained release, retention behavior and biocompatibility are validated, combined with assessments of cardiac function, histology, fibrosis and Foxp3⁺ Treg analysis. Reduced infarction and fibrosis together with Treg enrichment are observed in severe ischemia models. No significant functional improvement is seen in mild ischemia reperfusion models. The frequency of early immune cells shows no obvious alteration, whereas Tregs increase at later stages.

IV. Insights and Outlook
 (1) Reverse thinking: Locally recruit Tregs as an alternative to non specific immune suppression.
 (2) Systematic design: Combine microparticle mediated chemokine sustained release with hydrogelassisted retention for synergistic effects.
 (3) Platform potential: Compatible with diverse tissue adhesive / injectable hydrogels for local immunomodulation research targeting severe ischemic injuries.

V. Article Information
 (1) Journal source: Advanced Healthcare Materials, 2026
 (2) Article title: Topically Delivered Treg Attracting Microparticle Hydrogel Composites Recruit Regulatory T Cells and Limit Cardiac Injury After Severe Ischemia

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