A bioresorbable biomaterial carrier and passive stabilization device to improve heart function post-myocardial infarction

被引:61
|
作者
Dolan, Eimear B. [1 ,2 ,3 ,4 ,5 ]
Hofmann, Bjoern [6 ,7 ]
de Vaal, M. Hamman [6 ]
Bellavia, Gabriella [8 ]
Straino, Stefania [8 ]
Kovarova, Lenka [9 ,10 ]
Pravda, Martin [9 ]
Velebny, Vladimir [9 ]
Daro, Dorothee [11 ]
Braun, Nathalie [11 ]
Monahan, David S. [3 ]
Levey, Ruth E. [3 ]
O'Neill, Hugh [2 ]
Hinderer, Svenja [7 ,12 ]
Greensmith, Robert [4 ,5 ]
Monaghan, Michael G. [4 ,5 ]
Schenke-Layland, Katja [7 ,12 ]
Dockery, Peter [3 ]
Murphy, Bruce P. [4 ,5 ,13 ,14 ]
Kelly, Helena M. [1 ,2 ]
Wildhirt, Stephen [6 ]
Duffy, Garry P. [2 ,3 ,13 ,14 ]
机构
[1] Royal Coll Surgeons Ireland, Sch Pharm, 123 St Stephens Green, Dublin 2, Ireland
[2] Royal Coll Surgeons Ireland, Dept Anat, Tissue Engn Res Grp, 123 St Stephens Green, Dublin 2, Ireland
[3] Natl Univ Ireland Galway, Coll Med Nursing & Hlth Sci, Sch Med, Anat, Galway, Ireland
[4] Trinity Coll Dublin, Trinity Ctr Bioengn, Trinity Biomed Sci Inst, Dublin 2, Ireland
[5] Trinity Coll Dublin, Sch Engn, Dept Mech & Mfg Engn, Dublin 2, Ireland
[6] AdjuCor GmbH, Lichtenbergstr 8, D-85748 Garching, Germany
[7] Eberhard Karls Univ Tubingen, Dept Womens Hlth, Res Inst Womens Hlth, Silcherstr 7-1, D-72076 Tubingen, Germany
[8] Explora Biotech Srl, G Peroni 386, I-00131 Rome, Italy
[9] Contipro, R&D Dept, Dolni Dobrouc 401, Dolni Dobrouc 56102, Czech Republic
[10] Brno Univ Technol, Fac Chem, Inst Phys Chem, Purkynova 464-118, Brno 61200, Czech Republic
[11] Celyad SA, Mont St Guibert, Belgium
[12] Univ Tubingen, Nat & Med Sci Inst NMI, Markwiesenstr 55, D-72770 Reutlingen, Germany
[13] Trinity Coll Dublin, Royal Coll Surg Ireland, Adv Mat & BioEngn Res Ctr AMBER, Dublin, Ireland
[14] Natl Univ Ireland Galway, Galway, Ireland
关键词
Ventricular stabilization; Epicardial carrier device; Extravascular device; Hyaluronic acid hydrogel; Stem cell delivery; Myocardial infarction; VENTRICULAR RESTRAINT THERAPY; ACUTE MYOCARDIAL-INFARCTION; PROGENITOR CELLS; STEM-CELLS; GROWTH-FACTOR; HYDROGELS; DEGRADATION; DELIVERY; HYALURONAN; INJECTION;
D O I
10.1016/j.msec.2019.109751
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
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.
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页数:17
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