Mechano-matching hydrogel patch promotes myocardial infarction repair via YAP-Bcl-2 pathway activation

Area of Science:

• Biomaterials Science
• Cardiovascular Research
• Mechanobiology

Background:

• Elastic cardiac patches show promise for myocardial infarction (MI) recovery.
• The precise mechanisms behind their therapeutic effects are not fully understood.

Purpose of the Study:

• To investigate the impact of varying hydrogel elastic moduli on cardiac function post-MI.
• To elucidate the mechanotransduction pathways responsible for the therapeutic benefits of cardiac patches.

Main Methods:

• Fabrication of acellular hydrogel patches with soft (1.61 kPa), mechano-matching (16.82 kPa), and rigid (602.61 kPa) moduli.
• Implantation of patches in a rat model of MI.
• Establishment of an in vitro cyclic stretch model to study cardiomyocyte mechanotransduction.

Main Results:

• The mechano-matching hydrogel patch significantly improved cardiac function (LVEF increase), reduced infarct size, myocardial fibrosis, and cardiomyocyte apoptosis.
• Moderate stiffness hydrogels promoted nuclear translocation of YAP in cardiomyocytes via mechanotransduction.
• This process upregulated Bcl-2 expression, suppressing cardiomyocyte apoptosis.

Conclusions:

• Acellular cardiac patches with mechano-matching stiffness confer cardioprotection post-MI by activating the YAP-Bcl-2 signaling axis.
• The intrinsic mechanical properties of biomaterials alone can reverse pathological myocardial remodeling.
• This mechanobiology-guided approach enhances the clinical translatability of acellular cardiac patches for cardiac regeneration.