Ameliorating post-infarction myocardial fibrosis and cardiac function via ROS-responsive hydrogel-mediated IL-11 antibody delivery.

You, Ting; Zhang, Yong; Su, Haotao; Wang, Na; Zhang, Xinkui; Anwaier, Sainiwaier; Long, Xiang; Han, Linjiang et al. · Bioact Mater · 2026

basic_science · Level V

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Abstract

Myocardial fibrosis, driven by fibroblast activation following myocardial infarction (MI), represents a significant pathological process contributing to heart failure progression. Interleukin-11 (IL-11) is recognized as a key mediator in fibrotic pathologies across multiple organs, including the heart. This study demonstrates consistent and specific upregulation of IL-11 expression in a mouse MI model. A single intrapericardial injection of the IL-11-blocking antibody hIL-11 MAB resulted in a modest attenuation of post-MI fibrosis. Subsequently, encapsulation of hIL-11 MAB within reactive oxygen species (ROS)-sensitive hydrogels significantly prolonged drug retention at the injury site, leading to markedly improved therapeutic efficacy. Hydrogel-delivered hIL-11 MAB effectively preserved cardiac structure and function by reducing scar fibrosis, specifically decreasing scar thickness and marginal zone area. IL-11 blockade mediated reduced collagen deposition and enhanced left ventricular contractility, concomitant with a decrease in fibrotic tissue stiffness. These findings provide compelling evidence supporting IL-11 as a therapeutic target for myocardial fibrosis and highlight a novel delivery strategy for developing improved anti-fibrotic interventions.