Abstract 17861: Injectable Shear-thinning Hydrogels to Deliver Endothelial Progenitor Cells, Reduce Ventricular Strain, and Dynamic Stiffness to Stabilize Cardiac Function Following Ischemic Injury
The ventricle undergoes adverse remodeling, post-infarction. We developed an injectable shear-thinning hyaluronic acid hydrogel(STG) and endothelial progenitor cell construct(STG-EPC) to enhance vasculogenesis(shown previously) and mechanically stabilize the infarcted myocardium. We hypothesize that this tissue-engineered therapy will minimize adverse remodeling and maintain myocardial tensile properties in a clinically translatable therapy.
EPCs(DiLDL+ VEGFR2+ CD34+) were harvested from adult Wistar Rats and suspended in STG. STG-EPC constructs were circumferentially injected at the borderzone of ischemic rat myocardium, following LAD ligation. Engraftment and retention were assessed by near infrared cellular tag. Myocardial remodeling, tensile properties, and hemodynamic function were analyzed in 4 groups: control(PBS), EPC injection(EPC), STG injection(STG), and STG-EPC construct(STG-EPC). High-resolution ultrasound with speckle tracking (VSI Vevo 2100) allowed analysis of regional epicardial and endocardial strain. Uniaxial testing assessed tensile strength.
STG-EPC injection significantly increased engraftment, migration, and retention of the EPCs one-week post implant compared to EPC (0.7 vs 0.4 RFU, p=0.02). Using strain echocardiography a significant increase in left ventricular function was noted in the STG-EPC cohort. Strain echocardiography examination revealed a significant retention of myocardial longitudinal displacement with subsequent stabilization of myocardial velocity with STG-EPC therapy. A reduction in dynamic stiffness was noted in the STG-EPC cohort.(Table)
This novel injectable shear-thinning hyaluronic acid hydrogel seeded with EPCs demonstrates stabilization of borderzone myocardium with reduction in adverse myocardial remodeling and preservation of myocardial biomechanics. There is a markedly increased retention of delivered stem cells with this tissue engineered therapy.
Author Disclosures: A.C. Gaffey: None. M.H. Chen: None. A. Trubelja: None. C.M. Venkataraman: None. C.W. Chen: None. S. S: None. C.M. Sehgal: None. J.A. Burdick: None. P. Atluri: None.
- © 2015 by American Heart Association, Inc.