- •Preface
- •Acknowledgments
- •Introduction
- •Cardiac Tissue Engineering
- •Objectives and Scopes
- •Organization of the Monograph
- •Bibliography
- •Introduction
- •The Heart and Cardiac Muscle Structure
- •Myocardial Infarction and Heart Failure
- •Congenital Heart Defects
- •Endogenous Myocardial Regeneration
- •Potential Therapeutic Targets and Strategies to Induce Myocardial Regeneration
- •Bibliography
- •Introduction
- •Human Embryonic Stem Cells
- •Induced Pluripotent Stem Cells
- •Direct Reprogramming of Differentiated Somatic Cells
- •Cardiac Stem/Progenitor Cells
- •Summary and Conclusions
- •Bibliography
- •Introduction
- •Basic Biomaterial Design Criteria
- •Biomaterial Classification
- •Natural Proteins
- •Natural Polysaccharides
- •Synthetic Peptides and Polymers
- •Basic Scaffold Fabrication Forms
- •Hydrogels
- •Macroporous Scaffolds
- •Summary and Conclusions
- •Bibliography
- •Biomaterials as Vehicles for Stem Cell Delivery and Retention in the Infarct
- •Introduction
- •Stem Cell Delivery by Biomaterials
- •Cardiac Stem/Progenitor Cells
- •Clinical Trials
- •Summary and Conclusions
- •Bibliography
- •Introduction
- •Myocardial Tissue Grafts Created in Preformed Implantable Scaffolds
- •Summary and Conclusions
- •Bibliography
- •Introduction
- •Bioreactor Cultivation of Engineered Cardiac Tissue
- •Mass Transfer in 3D Cultures
- •Bioreactor as a Solution for Mass Transfer Challenge
- •Perfusion Bioreactors
- •Inductive Stimulation Patterns in Cardiac Tissue Engineering
- •Mechanotransduction and Physical/Mechanical Stimuli
- •Mechanical Stimulation Induced by Magnetic Field
- •Electrical Stimulation
- •Summary and Conclusions
- •Bibliography
- •Introduction
- •Prevascularization of the Patch by Incorporating Endothelial Cells (ECs)
- •The Body as a Bioreactor for Patch Vascularization
- •Summary and Conclusions
- •Bibliography
- •Introduction
- •Decellularized ECM
- •Injectable Biomaterials
- •Injectable hydrogels based on natural or synthetic polymers
- •Injectable Decellularized ECM Matrices
- •Mechanism of Biomaterial Effects on Cardiac Repair
- •Immunomodulation of the Macrophages by Liposomes for Infarct Repair
- •Inflammation, Apoptosis, and Macrophage Response after MI
- •Summary and Conclusions
- •Bibliography
- •Introduction
- •Evolution of Bioactive Material Approach for Myocardial Regeneration
- •Bioactive Molecules for Myocardial Regeneration and Repair
- •Injectable Systems
- •Sulfation of Alginate Hydrogels and Analysis of Binding
- •Injectable Affinity-Binding Alginate Biomaterial
- •Summary and Conclusions
- •Bibliography
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].