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'''Injection of Biomaterial, Alginate, into Ischemic Tissue Post Myocardial Infarction to Limit Left Ventricular Remodeling and Improve Function '''

Left ventricular remodeling after a myocardial infarction (MI) involves degradation of the extracellular matrix (ECM) with activated matrix metalloproteases (MMPs), expansion of the infarction, scar thinning, and the eventual transition into heart failure (Leor et al., 2000)(Christman, Lee, 2006). Injection of biomaterials such as alginate, fibrin or collagen, directly into the infarct area can limit left ventricular remodeling that occurs post MI (Leor et al., 2000).

Alginate is a polysaccharide found in brown seaweed. In infracted hearts alginate is used in the form of a cross-linked hydrogel, which gives it a structure similar to the ECM (Landa et al., 2008). An aqueous solution of calcium cross-linked alginate has been developed, which displays a low viscosity at room temperature. Once the biomaterial is injected into the infarct, a phase transition occurs as the calcium ion concentration increases, allowing a hydrogel to form (Landa et al., 2008). Over time, the hydrogel dissolves and disappears, as the kidneys excrete the water-soluble alginate (Landa et al., 2008).

A study done in rats determined the distribution of biotin labeled calcium cross-linked alginate after post-MI injection and examined the effects of both early (7 days post MI) and late (2 months post MI) injection of biomaterial on left ventricular remodeling and function (Landa et al., 2009). Biotin labeled alginate showed that it occupied ~45% of the infarct area within 1 hour of injection (Landa et al., 2009). At 1, 4 and 6 weeks after the injection, the area of the scar occupied by the alginate was significantly decreased. Microscopically, an unspecified but significant amount of alginate was found 1 hour and 1 week after injection (Landa et al., 2009). Very little alginate was present after four and six weeks, and scar tissue was largely replaced by connective tissue and myofibroblasts (Landa et al., 2009). The alginate provided mechanical and physical support to the damaged tissue after MI and replaced some of the function of the damaged ECM (Landa et al., 2009). This provided physical scaffolding and stabilized the infarct to prevent dilation, expansion, and potential ruptures (Landa et al., 2009). Alginate increased scar thickness leading to stabilizing the size of the ventricle. This also decreased the adverse cardiac remodeling, and systolic and diastolic dysfunction (Landa et al., 2009). Thickening of scar area reduces the amount of wall stress, as well as the amount of outward motion of the infarct that occurs during contraction (Landa et al., 2009). Therefore administration of alginate into the infarction area proved to improve cardiac function after a myocardial infarction regardless whether it was injected within hours or weeks of MI.

Alginate biomaterials have an advantage because they are non-thrombotic (Leor, et al., 2009). If the material allowed blood clots to form that would increase the chance of developing another myocardial infarction. A study done in swine found that intracoronary injection of alginate localized the gelation as a scaffold to the damaged tissue and prevented dysfunctional LV remodeling(Leor, et al., 2009). Most previous studies had examined direct injection into the heart. The intracoronary injection method had never been studied before, but it was demonstrated to reduce mechanical complications, heart failure and death, offering an alternative approach to treat patients post-MI. (Leor et al. 2009).

Christman, K.L., Lee, R.L. Biomaterials for the Treatment of Myocardial Infarction. Journal of American College of Cardiology. 48 (5): 907-913. (2006).

Landa, N., Miller, L., Feinberg, M.S., Holbova, R., Shachar, M., Freeman, I., Cohen, S., Leor, J. Effect of Injectable Alginate Implant on Cardiac Remodeling and Function After Recent and Old Infarcts in Rat. Circulation. 117: 1388-1396. (2008).

Leor, J., Aboulafia-Etzion, S., Dar, A., Shapiro, L., Barbash, I.M., Battler, A., Granot, Y., Cohen, S. Bioengineered Cardiac Grafts: A New Approach to Repair the Infarcted Myocardium? Circulation. 102 (suppl. 3): 54-61. (2000).

Leor, J., Tuvia, S., Guetta, V., Manczur, F., Castle, D., Willenz, U., Petnehazy, O., Landa, N., Feinberg, M.S., Konen, E., Goitein, O., Tsur-Gang, O., Shaul, M., Klapper, L., Cohen, S. Intracoronary Injection of In Situ Foming Alginate Hydrogel Reverses Left Ventricular Remodeling After Myocardial Infarction in Swine. Journal of the American College of Cardiology. 54 (11):1014-1022. (2009).