Injectable Shear-Thinning Hydrogels Prevent Ischemic Mitral Regurgitation and Normalize Ventricular Flow Dynamics

Area of Science:

• Biomaterials Science
• Cardiovascular Research
• Regenerative Medicine

Background:

• Myocardial infarction (MI) often leads to left-ventricular (LV) remodeling and ischemic mitral regurgitation (IMR).
• Injectable hydrogels are explored for attenuating LV remodeling, but their impact on post-MI IMR is less understood.
• Material mechanical properties of hydrogels are crucial for their efficacy in cardiac applications.

Purpose of the Study:

• To evaluate the efficacy of injectable hydrogels with tunable modulus in preventing post-MI IMR.
• To assess the impact of hydrogel injection on LV remodeling, valve geometry, and intraventricular flow dynamics.
• To determine if hydrogel stiffness influences the prevention of IMR and restoration of cardiac function.

Main Methods:

• Posterolateral MI was induced in 20 sheep, followed by epicardial injection of saline, soft hydrogel (<1 kPa), or stiff hydrogel (41.4 ± 4.3 kPa).
• Echocardiography assessed IMR and valve geometry; magnetic resonance imaging evaluated LV geometry and ventricular flow dynamics over 8 weeks.
• Statistical analysis, including Spearman correlation, was used to correlate IMR with geometric and hemodynamic parameters.

Main Results:

• IMR developed in control (MI) sheep and was significantly attenuated by both soft and stiff hydrogel treatments (P=0.02).
• Stiff hydrogel treatment prevented posterior leaflet tethering and normalized intraventricular flow patterns, reducing regurgitant volumes.
• IMR severity correlated with increased LV long-axis dimension (R=0.77) and posterior chordae length (R=0.64).

Conclusions:

• Injectable hydrogels, particularly those with supraphysiological modulus, effectively attenuate subvalvular remodeling and leaflet tethering post-MI.
• Hydrogel treatment prevents the development of IMR and normalizes LV flow dynamics, offering a promising therapeutic strategy.
• Tunable mechanical properties of hydrogels are critical for optimizing outcomes in treating post-myocardial infarction cardiac dysfunction.