A tripartite therapeutic agent reprograms the myocardial infarction microenvironment.

Area of Science:

• Biomaterials Science
• Cardiovascular Research
• Regenerative Medicine

Background:

• Myocardial infarction (MI) poses a significant global health burden, with recovery hindered by oxidative stress, inflammation, and electrical abnormalities.
• Current reperfusion therapies for MI have limitations in addressing the complex post-infarction pathological cascade.
• Developing effective strategies for myocardial repair is crucial to improve functional outcomes after heart attacks.

Purpose of the Study:

• To develop and evaluate a multifunctional myocardial repair agent (MMRA) for treating myocardial infarction.
• To assess the therapeutic potential of a composite hydrogel system combining anti-inflammatory, antioxidant, and conductive properties.
• To investigate the agent's ability to modulate the post-infarction microenvironment and restore cardiac function.

Main Methods:

• Formulation of a multifunctional myocardial repair agent (MMRA) using polypyrrole, sinomenine (Sino), and a thermoresponsive Poloxamer 407 (P407) hydrogel.
• Utilizing an injectable P407 hydrogel for targeted delivery and sustained release of therapeutic components into the infarct zone.
• Conducting in vivo evaluations to assess the MMRA's effects on reactive oxygen species, inflammatory cytokines, macrophage polarization, and electrical signal propagation.

Main Results:

• The MMRA effectively scavenged reactive oxygen species and reduced pro-inflammatory cytokines.
• Macrophage polarization was reprogrammed towards a tissue-reparative M2 phenotype.
• Electrical signal propagation was restored via conductive hydrogel-mediated intercellular coupling, preserving electromechanical synchronization.

Conclusions:

• The developed MMRA offers a tripartite therapeutic strategy for myocardial infarction, addressing key pathological mechanisms.
• The agent's ability to modulate the cardiac microenvironment and synchronize electrical activity holds significant potential for enhancing myocardial repair.
• The use of clinically approved components (Sino and P407) highlights the translational feasibility of this approach for MI treatment.