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.
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.
Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109751. doi: 10.1016/j.msec.2019.109751. Epub 2019 May 15.
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.
心肌梗死后，心脏的再生能力有限，导致重构过程进展为充血性心力衰竭（CHF）。已经出现了几种策略，包括机械稳定脆弱的心肌和再生方法（特别是干细胞技术），旨在预防 CHF。然而，它们的最终性能仍然有限，这促使人们需要一种具有增强疗效和减少有害作用的先进策略。一种心外膜载体装置可以实现将基于生物材料的治疗靶向应用于心梗心室壁，从而有可能克服治疗和应用相关问题。这种装置在心再生中可以发挥协同作用，包括为重构的心肌壁提供机械支持，以及为原位干细胞递送提供合适的环境，从而可能促进心脏再生。在这项研究中，我们开发了一种新颖的、单阶段的概念，通过微创、闭合性胸部干预在心外膜心脏表面应用弹性、可生物降解的补丁（SPREADS）来支持 MI 后的脆弱心肌区域。与 GS（临床金标准治疗）相比，GS+SPREADS+Gel 加或不加细胞的治疗后 14 天的 %LVEF 显著增加（p≤0.001）。此外，我们没有发现任何组之间的梗死质量或血管密度有显著差异，这表明 SPREADS 既不是梗死质量也不是血管生成的作用机制。SPREADS 装置有可能用于递送一系列新的或以前开发的生物材料水凝胶，这为克服水凝胶递送到心脏的转化障碍提供了巨大的潜力。
