Injectable Hydrogels for Minimally Invasive Delivery to Limit Infarct Induced Left Ventricular Remodeling and Mitral Regurgitation

Introduction and Hypothesis: Injectable hydrogels limit LV remodeling and progressive heart failure post-MI by bulking and stiffening the infarct to reduce wall stress. A material with therapeutic properties (high stiffness, slow degradation) that can be delivered percutaneously has not been demonstrated. We investigated the hypothesis that soft guest-host (GH) hydrogels would allow catheter delivery and that stiffening (dual-crosslinking, DC) would enhance treatment efficacy. Methods: To obtain GH hydrogels, hyaluronic acid (HA) was modified by adamantane (Ad-HA) or β-cyclodextrin (CD-HA). For DC hydrogels, thiolated Ad-HA and methacrylated CD-HA were prepared. Degradation and moduli were measured in vitro. Posterolateral infarct was induced by coronary ligation in an ovine model, and 16 injections (4.8 mL total) of saline, GH, or DC hydrogel were made into the infarct (Fig 1A,B; n≥6 /group). Myocardial stress was investigated with finite element modeling (FEM). In vivo, outcomes were measured by echocar...