2025-11-14 テキサスA&M大学
<関連情報>
- https://stories.tamu.edu/news/2025/11/14/healing-the-heart-after-a-heart-attack/
- https://www.cell.com/cell-biomaterials/fulltext/S3050-5623(25)00143-6
齧歯類およびブタの心筋梗塞モデルにおける心臓修復のための免疫調節性マイクロニードルパッチ Immunomodulatory microneedle patch for cardiac repair in rodent and porcine models of myocardial infarction
Ke Huang ∙ Dashuai Zhu, ∙ Jennifer Soto ∙ … ∙ Zhen Gu ∙ Song Li ∙ Ke Cheng
Cell Biomaterials Published:July 23, 2025
DOI:https://doi.org/10.1016/j.celbio.2025.100152
The bigger picture
Myocardial infarction (MI) remains a major cause of extensive myocardial necrosis and consequent impairment of cardiac contractile function, which progressively deteriorates and may ultimately lead to heart failure. Macrophages regulate the balance between deterioration and healing processes of an MI-injured heart through the dynamics of polarization. Interleukin-4 (IL-4) is well established for its role in directing macrophages toward a pro-regenerative state, with some foundational studies confirming its therapeutic benefits for heart repair. However, the successful translation of IL-4 therapies to modulate macrophages in vivo faces the challenge of achieving sustained and minimally invasive delivery of IL-4 locally to the injured myocardium. In this study, we encapsulated IL-4 within poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) and loaded them into a hyaluronic acid (HA) hydrogel-based microneedle (MN) patch. This design offers biocompatibility, tunable release kinetics, formulation versatility, and controlled release, while the microneedle architecture serves as a conduit to penetrate the condensed epicardium and facilitate targeted diffusion of IL-4 into the injured myocardium. Additionally, the entire system (IL-4 MP-MN) allows for safe degradation in situ without requiring surgical retrieval. The application of IL-4 MP-MN effectively modulated post-MI immune dynamics and promoted cardiac tissue repair. Notably, a cell state change in cardiomyocytes resulted in the preservation of cardiac function, enhanced morphological outcomes, and increased proliferative capacity. Additionally, the efficacy and safety outcomes from the large animal trials emphasized advancement toward the potential clinical adoption of the IL-4 MP-MN therapeutic strategy.
Graphical abstract
Highlights
- IL-4 MP-MN patch enables localized and sustained IL-4 delivery to an MI heart
- The patch improves heart function and structure in rat and porcine MI models
- The patch induces a macrophage-associated pro-reparative microenvironment
- The patch promotes a shift in the cardiomyocyte state toward cell-cycle re-entry
Summary
This study introduces a hyaluronic acid hydrogel-based microneedle patch embedded with interleukin-4 (IL-4)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles. This highly biodegradable cardiac patch is for localized immunomodulation and cardiac repair following acute myocardial infarction (MI). This patch enables sustained IL-4 release, thereby fostering a macrophage-mediated pro-reparative microenvironment that promotes cardiomyocyte re-entry into the cell cycle and attenuates endothelial inflammatory signaling. In both rat and porcine MI models, this treatment significantly improved cardiac function and preserved myocardial structure. These findings highlight the translational potential of this patch as a therapeutic strategy for heart repair during the acute phase of MI.
