Journal article
Abstract 18710: Injectable Hydrogels for Minimally Invasive Delivery to Limit Infarct Induced Left Ventricular Remodeling and Mitral Regurgitation
Circulation (New York, N.Y.), Vol.134(Suppl_1 Suppl 1), pp.A18710-A18710
11 Nov 2016
Abstract
Introduction and HypothesisInjectable 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.MethodsTo 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 echocardiographic grading of mitral regurgitation (MR, 0, 8 wk), MRI (0, 2, 8 wk), and histological and PCR analysis (8 wk).Results and ConclusionsDC hydrogels degraded slower than GH hydrogels and had increased moduli (41.2±4.3 vs <1 kPa). In FEM, wall stress was reduced by >50% with DC hydrogels. Infarct thickness improved with treatments (MI3.4 ± 0.2, GH5.5 ± 0.2, DC10.0 ± 0.8 mm at 8wk). In MI, LV end-systolic volume increased, ejection fraction declined, and MR increased; all outcomes improved with DC treatment (Fig 1C-E). Transforming growth factor beta expression was upregulated (41±4% by PCR, 8 wk) by DC treatment. Catheter-based delivery via endocardial injection was demonstrated. A hydrogel deliverable in a minimally-invasive manner was developed and showed effective reduction of LV remodeling metrics if stiffened by dual-crosslinking. These engineered materials have the potential to provide effective clinical options to treat patients after MI.
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- Title
- Abstract 18710: Injectable Hydrogels for Minimally Invasive Delivery to Limit Infarct Induced Left Ventricular Remodeling and Mitral Regurgitation
- Creators
- Christopher Rodell - University of South CarolinaMadonna LeeHua WangKia ZellarsPaige PerreaultJoseph GormanJonathan WenkFrancis SpinaleRobert GormanJason Burdick
- Publication Details
- Circulation (New York, N.Y.), Vol.134(Suppl_1 Suppl 1), pp.A18710-A18710
- Publisher
- by the American College of Cardiology Foundation and the American Heart Association, Inc
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Identifiers
- 991019341956904721