The limited regenerative capacity of the heart after a myocardial infarct results in remodeling processes that can progress to congestive heart failure (CHF). Several strategies including mechanical stabilization of the weakened myocardium and regenerative approaches (specifically stem cell technologies) have evolved which aim to prevent CHF. However, their final performance remains limited motivating the need for an advanced strategy with enhanced efficacy and reduced deleterious effects. An epicardial carrier device enabling a targeted application of a biomaterial-based therapy to the infarcted ventricle wall could potentially overcome the therapy and application related issues. Such a device could play a synergistic role in heart regeneration, including the provision of mechanical support to the remodeling heart wall, as well as providing a suitable environment for in situ stem cell delivery potentially promoting heart regeneration. In this study, we have developed a novel, single-stage concept to support the weakened myocardial region post-MI by applying an elastic, biodegradable patch (SPREADS) via a minimal-invasive, closed chest intervention to the epicardial heart surface. We show a significant increase in %LVEF 14 days post-treatment when GS (clinical gold standard treatment) was compared to GS + SPREADS + Gel with and without cells (p ≤ 0.001). Furthermore, we did not find a significant difference in infarct quality or blood vessel density between any of the groups which suggests that neither infarct quality nor vascularization is the mechanism of action of SPREADS. The SPREADS device could potentially be used to deliver a range of new or previously developed biomaterial hydrogels, a remarkable potential to overcome the translational hurdles associated with hydrogel delivery to the heart.

AdjuCor GmbH Lichtenbergstr 8 85748 Garching Germany

AdjuCor GmbH Lichtenbergstr 8 85748 Garching Germany; Eberhard Karls University Tübingen Department of Women's Health Research Institute for Women's Health Silcherstr 7 1 72076 Tübingen Germany

Anatomy School of Medicine College of Medicine Nursing and Health Sciences National University of Ireland Galway Ireland

Celyad SA Mont Saint Guibert Belgium

Eberhard Karls University Tübingen Department of Women's Health Research Institute for Women's Health Silcherstr 7 1 72076 Tübingen Germany; Natural and Medical Sciences Institute at the University of Tübingen Markwiesenstr 55 72770 Reutlingen Germany

Explora Biotech Srl G Peroni 386 00131 Rome Italy

R and D Department Contipro Dolni Dobrouc 401 561 02 Dolni Dobrouc Czech Republic

R and D Department Contipro Dolni Dobrouc 401 561 02 Dolni Dobrouc Czech Republic; Brno University of Technology Faculty of Chemistry Institute of Physical Chemistry Purkynova 464 118 612 00 Brno Czech Republic

School of Pharmacy Royal College of Surgeons in Ireland 123 St Stephen's Green Dublin 2 Ireland; Tissue Engineering Research Group Department of Anatomy Royal College of Surgeons in Ireland 123 St Stephen's Green Dublin 2 Ireland

School of Pharmacy Royal College of Surgeons in Ireland 123 St Stephen's Green Dublin 2 Ireland; Tissue Engineering Research Group Department of Anatomy Royal College of Surgeons in Ireland 123 St Stephen's Green Dublin 2 Ireland; Anatomy School of Medicine College of Medicine Nursing and Health Sciences National University of Ireland Galway Ireland; Trinity Centre for Bioengineering Trinity Biomedical Sciences Institute Trinity College Dublin Dublin 2 Ireland; Department of Mechanical and Manufacturing Engineering School of Engineering Trinity College Dublin Dublin 2 Ireland

Tissue Engineering Research Group Department of Anatomy Royal College of Surgeons in Ireland 123 St Stephen's Green Dublin 2 Ireland

Tissue Engineering Research Group Department of Anatomy Royal College of Surgeons in Ireland 123 St Stephen's Green Dublin 2 Ireland; Anatomy School of Medicine College of Medicine Nursing and Health Sciences National University of Ireland Galway Ireland; Advanced Materials and BioEngineering Research Centre Trinity College Dublin Royal College of Surgeons Ireland and National University of Ireland Galway Ireland

Trinity Centre for Bioengineering Trinity Biomedical Sciences Institute Trinity College Dublin Dublin 2 Ireland; Department of Mechanical and Manufacturing Engineering School of Engineering Trinity College Dublin Dublin 2 Ireland

Trinity Centre for Bioengineering Trinity Biomedical Sciences Institute Trinity College Dublin Dublin 2 Ireland; Department of Mechanical and Manufacturing Engineering School of Engineering Trinity College Dublin Dublin 2 Ireland; Advanced Materials and BioEngineering Research Centre Trinity College Dublin Royal College of Surgeons Ireland and National University of Ireland Galway Ireland

References provided by Crossref.org

Combining Nanomaterials and Developmental Pathways to Design New Treatments for Cardiac Regeneration: The Pulsing Heart of Advanced Therapies