Targeted Myocardial Microinjections of a Biocomposite Material Reduces Infarct Expansion in Pigs

Mukherjee, Rupak; Zavadzkas, Juozas A.; Saunders, Stuart M; McLean, Julie E.; Jeffords, Laura B.; Beck, Christy; Stroud, Robert E.; Leone, A; Koval, Christine N.; Rivers, William T; Basu, Shubhayu; Sheehy, Alexander; Michal, Gene; Spinale, Francis G.

doi:10.1016/j.athoracsur.2008.04.107

Cited by 100 publications

(128 citation statements)

References 28 publications

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“…Fibrin has natural binding domains for soluble growth factors and cellular integrin receptors, motivating its use for wound healing applications. Although fibrin is commonly utilized for these biological properties, it can also be used as a mechanical support for the myocardium [18,29,34,48]. Specifically, fibrin forms a crosslinked 3-D hydrogel in the myocardium upon injection with a dual-barreled syringe.…”

Section: Natural Hydrogelsmentioning

confidence: 99%

“…Specifically, fibrin forms a crosslinked 3-D hydrogel in the myocardium upon injection with a dual-barreled syringe. One barrel contains fibrinogen and aprotinin, a fibrinolysis inhibitor, and the second barrel contains thrombin, factor XIIIa, and CaCl 2 [18,23,29,48]. Following a similar mechanism to that involved in the normal clotting cascade in vivo, when fibrinogen and thrombin are mixed, fibrinogen is converted to fibrin which self-assembles and is crosslinked via the factor XIIIa.…”

Section: Natural Hydrogelsmentioning

confidence: 99%

“…Utilizing a large animal swine model, Mukherjee et al injected composite hydrogels containing both fibrin and alginate to prevent geometric LV remodeling [29]. One week post-MI, 200 μL injections (25 total) were applied to the infarct area via a double-barreled injection device; one component was comprised of fibrinogen, fibronectin, factor XIII, plasminogen, and gelatin-grafted alginate dissolved in an aprotinin solution, while the second consisted of thrombin and 40 mM CaCl 2 .…”

Section: Natural Hydrogelsmentioning

confidence: 99%

“…If anything, these results reveal the complexity in the material interaction with the myocardial tissue, including both the biological (e.g., material remodeling and inflammatory response) and mechanical (e.g., stress reduction) responses. Variable results from these studies indicate that material thickness [21,26,29,34], infarct size [22] [34], and/or increased angiogenesis [19,24,64] do not necessarily correlate directly with improved heart function. However, discrepancies in results could be due to inconsistencies in methodology (Table 1; e.g., animal models, infarct, amount of material injected, and timing of injection), and material properties and the importance of these parameters should be considered when investigating LV remodeling.…”

Section: Limitations Of Experimental Assessment Of Bulking Agentsmentioning

confidence: 99%

“…However, these approaches are limited by the invasive procedure in which they are applied, and clinical adoption has not occurred. In order to circumvent the invasive surgical placement of restraining devices early post-MI, our group and others have begun to explore the use of injectable materials, and specifically hydrogels, to limit infarct expansion and normalize the regional stress distribution [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

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Injectable Acellular Hydrogels for Cardiac Repair

Tous

Purcell

Ifkovits

et al. 2011

J. of Cardiovasc. Trans. Res.

152

136

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Injectable hydrogels are being developed as potential translatable materials to influence the cascade of events that occur after myocardial infarction. These hydrogels, consisting of both synthetic and natural materials, form through numerous chemical crosslinking and assembly mechanisms and can be used as bulking agents or for the delivery of biological molecules. Specifically, a range of materials are being applied that alter the resulting mechanical and biological signals after infarction and have shown success in reducing stresses in the myocardium and limiting the resulting adverse left ventricular (LV) remodeling. Additionally, the delivery of molecules from injectable hydrogels can influence cellular processes such as apoptosis and angiogenesis in cardiac tissue or can be used to recruit stem cells for repair. There is still considerable work to be performed to elucidate the mechanisms of these injectable hydrogels and to optimize their various properties (e.g., mechanics and degradation profiles). Furthermore, although the experimental findings completed to date in small animals are promising, future work needs to focus on the use of large animal models in clinically relevant scenarios. Interest in this therapeutic approach is high due to the potential for developing percutaneous therapies to limit LV remodeling and to prevent the onset of congestive heart failure that occurs with loss of global LV function. This review focuses on recent efforts to develop these injectable and acellular hydrogels to aid in cardiac repair.

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Section: Natural Hydrogelsmentioning

confidence: 99%

Section: Natural Hydrogelsmentioning

confidence: 99%

Section: Natural Hydrogelsmentioning

confidence: 99%

Section: Limitations Of Experimental Assessment Of Bulking Agentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Injectable Acellular Hydrogels for Cardiac Repair

Tous

Purcell

Ifkovits

et al. 2011

J. of Cardiovasc. Trans. Res.

152

136

View full text Add to dashboard Cite

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Clinical Uses of Alginate

Nussinovitch

2011

Biodegradable Polymers in Clinical Use and Clinical Development

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Cardiomyocyte Induction and Regeneration for Myocardial Infarction Treatment: Cell Sources and Administration Strategies

Chen

2020

Adv Healthcare Materials

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Occlusion of coronary artery and subsequent damage or death of myocardium can lead to myocardial infarction (MI) and even heart failure-one of the leading causes of deaths world wide. Notably, myocardium has extremely limited regeneration potential due to the loss or death of cardiomyocytes (i.e., the cells of which the myocardium is comprised) upon MI. A variety of stem cells and stem cell-derived cardiovascular cells, in situ cardiac fibroblasts and endogenous proliferative epicardium, have been exploited to provide renewable cellular sources to treat injured myocardium. Also, different strategies, including direct injection of cell suspensions, bioactive molecules, or cell-incorporated biomaterials, and implantation of artificial cardiac scaffolds (e.g., cell sheets and cardiac patches), have been developed to deliver renewable cells and/or bioactive molecules to the MI site for the myocardium regeneration. This article briefly surveys cell sources and delivery strategies, along with biomaterials and their processing techniques, developed for MI treatment. Key issues and challenges, as well as recommendations for future research, are also discussed.

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Targeted Myocardial Microinjections of a Biocomposite Material Reduces Infarct Expansion in Pigs

Abstract: Background-Left ventricular (LV) remodeling after myocardial infarction (MI) commonly causes infarct expansion (IE). This study sought to interrupt IE through microinjections of a biocompatible composite material into the post-MI myocardium.

Cited by 100 publications

References 28 publications

Injectable Acellular Hydrogels for Cardiac Repair

Injectable Acellular Hydrogels for Cardiac Repair

Clinical Uses of Alginate

Cardiomyocyte Induction and Regeneration for Myocardial Infarction Treatment: Cell Sources and Administration Strategies

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