title: Hydrogels with integrin-binding angiopoietin-1-derived peptide, QHREDGS, for treatment of acute myocardial infarction.
abstract: BACKGROUND
  Hydrogels are being actively investigated for direct delivery of cells or bioactive molecules to the heart after myocardial infarction (MI) to prevent cardiac functional loss. We postulate that immobilization of the prosurvival angiopoietin-1-derived peptide, QHREDGS, to a chitosan-collagen hydrogel could produce a clinically translatable thermoresponsive hydrogel to attenuate post-MI cardiac remodeling.
  
  
  RESULTS
  In a rat MI model, QHREDGS-conjugated hydrogel (QHG213H), control gel, or PBS was injected into the peri-infarct/MI zone. By in vivo tracking and chitosan staining, the hydrogel was demonstrated to remain in situ for 2 weeks and was cleared in ≈3 weeks. By echocardiography and pressure-volume analysis, the QHG213H hydrogel significantly improved cardiac function compared with the controls. Scar thickness and scar area fraction were also significantly improved with QHG213H gel injection compared with the controls. There were significantly more cardiomyocytes, determined by cardiac troponin-T staining, in the MI zone of the QHG213H hydrogel group; and hydrogel injection did not induce a significant inflammatory response as assessed by polymerase chain reaction and an inflammatory cytokine assay. The interaction of cardiomyocytes and cardiac fibroblasts with QHREDGS was found to be mediated by β1-integrins.
  
  
  CONCLUSIONS
  We demonstrated for the first time that the QHG213H peptide-modified hydrogel can be injected in the beating heart where it remains localized for a clinically effective period. Moreover, the QHG213H hydrogel induced significant cardiac functional and morphological improvements after MI relative to the controls.
authors: From the Institute of Biomaterials and Biomedical Engineering (L.A.R., N.F., C.L., M.R.) and Department of Chemical Engineering and Applied Chemistry (L.L.Y.C., M.R.), University of Toronto, Canada; and Toronto General Research Institute, University Health Network, Canada (J.W., A.M., R.-K.L.).
authors: Lewis A
authors: LA
authors: Reis
authors: From the Institute of Biomaterials and Biomedical Engineering (L.A.R., N.F., C.L., M.R.) and Department of Chemical Engineering and Applied Chemistry (L.L.Y.C., M.R.), University of Toronto, Canada; and Toronto General Research Institute, University Health Network, Canada (J.W., A.M., R.-K.L.).
authors: Loraine L Y
authors: LL
authors: Chiu
authors: From the Institute of Biomaterials and Biomedical Engineering (L.A.R., N.F., C.L., M.R.) and Department of Chemical Engineering and Applied Chemistry (L.L.Y.C., M.R.), University of Toronto, Canada; and Toronto General Research Institute, University Health Network, Canada (J.W., A.M., R.-K.L.).
authors: Jun
authors: J
authors: Wu
authors: From the Institute of Biomaterials and Biomedical Engineering (L.A.R., N.F., C.L., M.R.) and Department of Chemical Engineering and Applied Chemistry (L.L.Y.C., M.R.), University of Toronto, Canada; and Toronto General Research Institute, University Health Network, Canada (J.W., A.M., R.-K.L.).
authors: Nicole
authors: N
authors: Feric
authors: From the Institute of Biomaterials and Biomedical Engineering (L.A.R., N.F., C.L., M.R.) and Department of Chemical Engineering and Applied Chemistry (L.L.Y.C., M.R.), University of Toronto, Canada; and Toronto General Research Institute, University Health Network, Canada (J.W., A.M., R.-K.L.).
authors: Carol
authors: C
authors: Laschinger
authors: From the Institute of Biomaterials and Biomedical Engineering (L.A.R., N.F., C.L., M.R.) and Department of Chemical Engineering and Applied Chemistry (L.L.Y.C., M.R.), University of Toronto, Canada; and Toronto General Research Institute, University Health Network, Canada (J.W., A.M., R.-K.L.).
authors: Abdul
authors: A
authors: Momen
authors: From the Institute of Biomaterials and Biomedical Engineering (L.A.R., N.F., C.L., M.R.) and Department of Chemical Engineering and Applied Chemistry (L.L.Y.C., M.R.), University of Toronto, Canada; and Toronto General Research Institute, University Health Network, Canada (J.W., A.M., R.-K.L.).
authors: Ren-Ke
authors: RK
authors: Li
authors: From the Institute of Biomaterials and Biomedical Engineering (L.A.R., N.F., C.L., M.R.) and Department of Chemical Engineering and Applied Chemistry (L.L.Y.C., M.R.), University of Toronto, Canada; and Toronto General Research Institute, University Health Network, Canada (J.W., A.M., R.-K.L.). m.radisic@utoronto.ca.
authors: Milica
authors: M
authors: Radisic
mesh_terms: D042683:Angiopoietin-1 / Q000737:chemistry*; D000818:Animals; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D016023:Integrins / Q000737:chemistry*; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011917:Rats, Inbred Lew
chemical_list: D042683:Angiopoietin-1; D020100:Hydrogels; D016023:Integrins; D010455:Peptides; D048271:Chitosan
keywords: chitosan; collagen; hydrogel; myocardial infarction