130 9. ACELLULAR BIOMATERIALS FOR CARDIAC REPAIR

Figure 9.1: (Continued.) Beneficial therapeutic effects of injectable alginate biomaterial on LV remodeling after MI in rats (B-E) and pigs (G-I). G. The effect of intracoronary injection of various volumes of alginate solution on LV dilation, 30 and 60 days after MI in pigs. Comparison of the therapeutic effects of intracoronary delivery of 1, 2, and 4 ml of alginate solution or saline (2 ml) into recent (4-day- old) scar. All volumes of alginate attenuate or prevent left ventricular (LV) diastolic (a) and systolic (b) dilation compared with control. Relative change was calculated as ([30 or or 60 day measure—3 day measure]/3 day measure) ×100. Individual values and mean (±SEM). The p values are for treatment effect versus control by repeated-measures analysis of variance (ANOVA) and Bonferroni post hoc test adjusted for multiple comparisons. H. Representative micrographs of infarcted hearts after immunostaining for α-SMA, 60 days after either alginate or saline injection. Examination of the scar tissues shows that (a) the alginate-treated scar is populated with numerous blood capillaries and myofibroblasts that are stained positive for α-SMA and (b) the saline treated scars show positive staining for α-SMA predominantly on the vessel walls. Reprinted with permission from [29, 30].

9.6MECHANISM OF BIOMATERIAL EFFECTS ON CARDIAC REPAIR

The possible mechanisms behind the beneficial effects of sole biopolymer injection are most likely related to the increase in scar thickness, early infarct stabilization, scaffolding, and critical physical support to the healing of LV, as well as replacement for the damaged ECM. All these effects are significant for reducing wall stress, prevention of LV dilatation, effective healing and repair. By thickening the scar, wall stress is reduced (by Laplace law) and the degree of outward motion of the infarct that occurs during systole (paradoxical systolic bulging) is also reduced. This is a significant effect, since one of the most important predictors of mortality in patients with MI is the degree of LV systolic dilatation.

The functional improvement seen after biomaterial treatment of the infarct was not accompanied by an actual induction of tissue regeneration, meaning without addition of new contractile units. This passive type of mechanical regeneration was confirmed by utilizing computational simulation models analyzing the impact of any material (ECM-like materials and/or cell masses) injection into infarcted myocardium [33]. Using a finite element (FE) model to simulate the effects of injecting a non-contractile material into the myocardium, Wall et al showed that bulking the myocardium was sufficient to attenuate post-MI geometric changes and, thus, to decrease stress in the myocardial wall. More specifically, they demonstrated that injections of 4.5% of the LV wall volume and 20% of the stiffness of the natural myocardium into the infarct border zone were able to decrease the fiber stress by 20% compared to control simulations with no injections [33].