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An injectable alginate/extra cellular matrix (ECM) hydrogel towards acellular treatment of heart failure

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Abstract

As treatments for myocardial infarction (MI) continue to improve, the population of people suffering from heart failure (HF) is rising significantly. Novel treatment strategies aimed at achieving long-term functional stabilisation and improvement in heart function post MI include the delivery of biomaterial hydrogels and myocardial matrix-based therapies to the left ventricle wall. Individually alginate hydrogels and myocardial matrix-based therapies are at the most advanced stages of commercial/clinical development for this potential treatment option. However, despite these individual successes, the potential synergistic effect gained by combining the two therapies remains unexplored. This study serves as a translational step in evaluating the minimally invasive delivery of dual acting alginate-based hydrogels to the heart. We have successfully developed new production methods for hybrid alginate/extracellular matrix (ECM) hydrogels. We have identified that the high G block alginate/ECM hybrid hydrogel has appropriate rheological and mechanical properties (1.6 KPa storage modulus, 29 KPa compressive modulus and 14 KPa dynamic modulus at day 1) and can be delivered using a minimally invasive delivery device. Furthermore, we have determined that these novel hydrogels are not cytotoxic and are capable of enhancing the metabolic activity of dermal fibroblasts in vitro (p < 0.01). Overall these results suggest that an effective minimally invasive HF treatment option could be achieved by combining alginate and ECM particles.

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Funding

AMCARE project funded by European Union’s ‘Seventh Framework’ Programme for research, technological development and demonstration under Grant Agreement no. NMP3-SME-2013-604531.

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Author notes

  1. Clive J. Curley and Eimear B. Dolan contributed equally to this work.

Authors and Affiliations

  1. Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland

    Clive J. Curley, Eimear B. Dolan, Garry P. Duffy & Bruce P. Murphy

  2. Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland

    Clive J. Curley, Eimear B. Dolan & Bruce P. Murphy

  3. Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin and Royal College of Surgeons Ireland, Dublin, Ireland

    Clive J. Curley, Garry P. Duffy & Bruce P. Murphy

  4. Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Ireland

    Eimear B. Dolan & Garry P. Duffy

  5. Department of Anatomy, School of Medicine, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland

    Eimear B. Dolan & Garry P. Duffy

  6. Department of Women’s Health, Research Institute for Women’s Health, Eberhard-Karls University, Silcherstrasse 7/1, 72076, Tübingen, Germany

    Matthias Otten & Svenja Hinderer

  7. Natural and Medical Sciences Institute (NMI), University of Tübingen, Markwiesenstraße 55, 72770, Reutlingen, Germany

    Svenja Hinderer

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  1. Clive J. Curley
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Correspondence to Bruce P. Murphy.

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Curley, C.J., Dolan, E.B., Otten, M. et al. An injectable alginate/extra cellular matrix (ECM) hydrogel towards acellular treatment of heart failure. Drug Deliv. and Transl. Res. 9, 1–13 (2019). https://doi.org/10.1007/s13346-018-00601-2

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