Injectable, Conductive, Multifunctional Hydrogels with Sustained Luteolin Release for Promoting Myocardial Infarction...

Area of Science:

• Biomaterials Science
• Cardiovascular Research
• Regenerative Medicine

Background:

• Myocardial infarction (MI) causes inflammation, oxidative stress, and electrical dysfunction, leading to adverse cardiac remodeling.
• Current treatments struggle to address these interconnected pathological processes comprehensively.

Purpose of the Study:

• To develop and evaluate an injectable conductive hydrogel (FLCM) for simultaneous treatment of multiple post-MI pathological challenges.
• To assess FLCM's efficacy in improving the cardiac microenvironment and restoring left ventricular function in a rat MI model.

Main Methods:

• FLCM was constructed using Pluronic F127 diacrylate, luteolin, collagen type I, and MXene nanosheets.
• In vitro and in vivo assessments in a rat MI model, including inflammatory cytokine analysis, macrophage polarization, oxidative stress markers, connexin 43 expression, arrhythmia monitoring, fibrosis assessment, and cardiac function evaluation.
• Transcriptomic profiling and protein-level validation were employed to elucidate underlying molecular mechanisms.

Main Results:

• FLCM demonstrated excellent injectability, conductivity, mechanical properties, and sustained drug release.
• FLCM implantation attenuated inflammation, reduced oxidative stress, preserved electrical coupling, and decreased ventricular arrhythmias.
• FLCM suppressed fibrosis, mitigated adverse cardiac remodeling, restored left ventricular function, and modulated key signaling pathways (PI3K-Akt, NF-κB, Nrf2/HO-1).

Conclusions:

• FLCM is an integrated hydrogel system that effectively targets multiple post-MI pathological processes.
• This multifunctional hydrogel offers a promising and translatable strategy for comprehensive cardiac repair and functional recovery after myocardial infarction.