Timing underpins the benefits associated with injectable collagen biomaterial therapy for the treatment of myocardial infarction

Blackburn, N.J.; Sofrenovic, Tanja; Kuraitis, Drew; Ahmadi, Ali; McNeill, Brian; Deng, Chao; Rayner, Katey J.; Zhong, Zhiyuan; Ruel, Marc; Suuronen, Erik J.

doi:10.1016/j.biomaterials.2014.11.004

Cited by 90 publications

(69 citation statements)

References 47 publications

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“…Furthermore, the time points evaluated in the current study correspond with the distinct remodeling phases in rat ventricular remodeling after MI. In the mouse model, and using a non-synthetic, collagen-based material, Blackburn et al recently reported injections at one time point in the necrotic phase (3 h) or one of two time points near the end of the fibrotic phase (1 or 2 w) [41]. They found that collagen injections at 3 h and 1 w after MI partially preserved cardiac function 4 w after treatment, and the 3 h injection favorably interacted with the early inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

et al. 2016

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Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes.

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Section: Discussionmentioning

confidence: 99%

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

et al. 2016

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“…This review provides an overview of recent advances and hurdles that remain to be overcome in the biomaterial design and engineering of various injectable hydrogel systems, with emphasis placed on systems being used in cardiac tissue engineering efforts. The articles that comprise the focus of this review are shown in Table 1 …”

Section: Introductionmentioning

confidence: 99%

Injectable Hydrogels for Cardiac Tissue Engineering

Peña

Laughter

Jett

et al. 2018

Macromolecular Bioscience

195

170

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In light of the limited efficacy of current treatments for cardiac regeneration, tissue engineering approaches have been explored for their potential to provide mechanical support to injured cardiac tissues, deliver cardio-protective molecules, and improve cell-based therapeutic techniques. Injectable hydrogels are a particularly appealing system as they hold promise as a minimally invasive therapeutic approach. Moreover, injectable acellular alginate-based hydrogels have been tested clinically in patients with myocardial infarction (MI) and show preservation of the left ventricular (LV) indices and left ventricular ejection fraction (LVEF). This review provides an overview of recent developments that have occurred in the design and engineering of various injectable hydrogel systems for cardiac tissue engineering efforts, including a comparison of natural versus synthetic systems with emphasis on the ideal characteristics for biomimetic cardiac materials.

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“…Su and coworkers recently showed that a vascularized biomimetic microvessel patch promoted cardiomyocyte proliferation and neovascularization post-infarction [120]. Injectable collagen-based biomaterials could provide mechanical support, improve angiogenesis and tissue integration and limit negative remodelling; [121] [122] however, further testing is necessary to limit risks to patients [123]. McLaughlin and coworkers recently developed a recombinant human collagen matrix that prevents adverse cardiac remodelling but improves ventricular function even when applied during the late proliferative phase [124].…”

Section: Heart Regenerationmentioning

confidence: 99%

Myocardial Infarction: Perspectives on Cardiac Regeneration and Cardiac Remote Conditioning Interventions to Limit Cellular Injury

Kingma¹

2020

WJCD

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Acute myocardial infarction initiates a cascade of events including loss of protein homeostasis and chronic inflammation that affect overall cellular repair and senescence. This contributes to loss of cardiomyocytes and consequent formation of fibrotic scar. In certain vertebrate species, the heart can completely self-repair or regenerate after myocardial injury; however, this does not appear to be the case for humans. Despite this limitation, studies using novel non-pharmacologic interventions designed to protect against ischemic damage and to improve patient outcomes are ongoing. Remote ischemic conditioning stratagems are used to attenuate ischemia-reperfusion injury in clinical and animal studies; endogenous protective factors that stimulate complex signal transduction pathways are deemed responsible. Some of these factors could conceivably act in concert with those involved in regulating cardiovascular regeneration. Numerous studies have focused on cardiac regenerative interventions using stem-cell based therapies and transplantation of cardiomyocyte (or other cell types) or biocompatible matrices. This review discusses recent progress of pre-clinical and clinical translational studies for cardiac regeneration. In addition, we submit that interventions using cellular adjunctive therapies combined with remote ischemic conditioning may prove to be of interest in the battle to find novel strategies for protection against cardiac injury. are described in the scientific literature; myocardial stunning, i.e. viable cardiomyocytes that exhibit prolonged post-ischemic contractile dysfunction even after reperfusion, and myocardial hibernation, i.e. viable, but chronically contractile dysfunctional cardiomyocytes. While the pathogenesis of cell death in non-cardiac cells is less considered in most studies, it is clear that vascular endothelial and smooth muscle cells along with nervous system components within the ischemic zone are negatively affected by coronary occlusion; this contributes significantly to overall loss of cardiac contractile function and limits recovery potential. Loss of these myocardial components probably renders the affected tissue non-salvageable for a number of reasons including no-reflow, or disrupted electrical conduction, etc. Timely reperfusion of the infarct-related artery by various clinical strategies (just enumerate them as reperfusion therapy which may be pharmacological, primary percutaneous coronary intervention, primary PCI, urgent coronary artery bypass graft, appears to limit overall myocardial damage; however, reperfusion itself may exacerbate injury via apoptosis or autophagy [19]. While patient survival after ischemia has markedly improved over the last forty years, the prevalence of chronic heart failure due, in part, to remodeling of the damaged left ventricle has also increased [20] [21]. Cardiac repair is a complex, tightly regulated process between innate and immune systems [22] that includes inflammation and infiltration of the infarct area by immune cell subtypes (neutro...

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Timing underpins the benefits associated with injectable collagen biomaterial therapy for the treatment of myocardial infarction

Cited by 90 publications

References 47 publications

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

Injectable Hydrogels for Cardiac Tissue Engineering

Myocardial Infarction: Perspectives on Cardiac Regeneration and Cardiac Remote Conditioning Interventions to Limit Cellular Injury

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