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Injectable Shear-Thinning Hydrogels for Minimally Invasive Delivery to Infarcted Myocardium to Limit Left Ventricular Remodeling.
Rodell, Christopher B; Lee, Madonna E; Wang, Hua; Takebayashi, Satoshi; Takayama, Tetsushi; Kawamura, Tomonori; Arkles, Jeffrey S; Dusaj, Neville N; Dorsey, Shauna M; Witschey, Walter R T; Pilla, James J; Gorman, Joseph H; Wenk, Jonathan F; Burdick, Jason A; Gorman, Robert C.
Afiliación
  • Rodell CB; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Lee ME; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Wang H; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Takebayashi S; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Takayama T; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Kawamura T; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Arkles JS; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Dusaj NN; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Dorsey SM; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Witschey WR; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Pilla JJ; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Gorman JH; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Wenk JF; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Burdick JA; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
  • Gorman RC; From the Department of Bioengineering (C.B.R., N.N.D., S.M.D., J.A.B.), Gorman Cardiovascular Research Group, Department of Surgery (M.E.L., S.T., T.T., T.K., J.S.A., J.H.G., R.C.G.), and Department of Radiology (W.R.T.W., J.J.P.), University of Pennsylvania, Philadelphia; and Department of Mechanic
Circ Cardiovasc Interv ; 9(10)2016 10.
Article en En | MEDLINE | ID: mdl-27729419
ABSTRACT

BACKGROUND:

Injectable, acellular biomaterials hold promise to limit left ventricular remodeling and heart failure precipitated by infarction through bulking or stiffening the infarct region. A material with tunable properties (eg, mechanics, degradation) that can be delivered percutaneously has not yet been demonstrated. Catheter-deliverable soft hydrogels with in vivo stiffening to enhance therapeutic efficacy achieve these requirements. METHODS AND

RESULTS:

We developed a hyaluronic acid hydrogel that uses a tandem crosslinking approach, where the first crosslinking (guest-host) enabled injection and localized retention of a soft (<1 kPa) hydrogel. A second crosslinking reaction (dual-crosslinking) stiffened the hydrogel (41.4±4.3 kPa) after injection. Posterolateral infarcts were investigated in an ovine model (n≥6 per group), with injection of saline (myocardial infarction control), guest-host hydrogels, or dual-crosslinking hydrogels. Computational (day 1), histological (1 day, 8 weeks), morphological, and functional (0, 2, and 8 weeks) outcomes were evaluated. Finite-element modeling projected myofiber stress reduction (>50%; P<0.001) with dual-crosslinking but not guest-host injection. Remodeling, assessed by infarct thickness and left ventricular volume, was mitigated by hydrogel treatment. Ejection fraction was improved, relative to myocardial infarction at 8 weeks, with dual-crosslinking (37% improvement; P=0.014) and guest-host (15% improvement; P=0.058) treatments. Percutaneous delivery via endocardial injection was investigated with fluoroscopic and echocardiographic guidance, with delivery visualized by magnetic resonance imaging.

CONCLUSIONS:

A percutaneous delivered hydrogel system was developed, and hydrogels with increased stiffness were found to be most effective in ameliorating left ventricular remodeling and preserving function. Ultimately, engineered systems such as these have the potential to provide effective clinical options to limit remodeling in patients after infarction.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Materiales Biocompatibles / Función Ventricular Izquierda / Remodelación Ventricular / Ácido Hialurónico / Infarto del Miocardio / Miocardio Tipo de estudio: Guideline / Prognostic_studies Límite: Animals Idioma: En Revista: Circ Cardiovasc Interv Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA Año: 2016 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Materiales Biocompatibles / Función Ventricular Izquierda / Remodelación Ventricular / Ácido Hialurónico / Infarto del Miocardio / Miocardio Tipo de estudio: Guideline / Prognostic_studies Límite: Animals Idioma: En Revista: Circ Cardiovasc Interv Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA Año: 2016 Tipo del documento: Article