Restoration of left ventricular geometry and improvement of left ventricular function in a rodent model of chronic ischemic cardiomyopathy

Abstract

Intramyocardially injected polymers can be used to reshape the aneurysmal left ventricle and might therefore be an approach for myocardial reconstruction and a potential option in treating chronic heart failure in human subjects.

Injectable Acellular Hydrogels for Cardiac Repair

“…Christman et al pioneered the field of acellular injectable biomaterials by exploring the effects of fibrin glue as a bulking agent [18,23,34,48]. Fibrin has natural binding domains for soluble growth factors and cellular integrin receptors, motivating its use for wound healing applications.…”

“…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.…”

“…Unlike fibrin, alginate must be modified with adhesive peptides to facilitate cell binding. Both non-modified alginate and alginate modified with adhesive peptides such as Arg-Gly-Asp (RGD) or Tyr-Ile-Gly-Ser-Arg (YIGSR) have been explored as bulking agents [26,31,34,50,51], and comparisons have been performed between the two [31,51]. Yu et al compared modified alginate to non-modified alginate using a rat reperfusion-MI model with injections 5 weeks post-MI, more indicative of a chronic response [51].…”

“…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.…”

“…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].…”