Minimally invasive cell-seeded biomaterial systems for injectable/epicardial implantation in ischemic heart disease

Abstract

Myocardial infarction (MI) is characterized by heart-wall thinning, myocyte slippage, and ventricular dilation. The injury to the heart-wall muscle after MI is permanent, as after an abundant cell loss the myocardial tissue lacks the intrinsic capability to regenerate. New therapeutics are required for functional improvement and regeneration of the infarcted myocardium, to overcome harmful diagnosis of patients with heart failure, and to overcome the shortage of heart donors. In the past few years, myocardial tissue engineering has emerged as a new and ambitious approach for treating MI. Several left ventricular assist devices and epicardial patches have been developed for MI. These devices and acellular/cellular cardiac patches are employed surgically and sutured to the epicardial surface of the heart, limiting the region of therapeutic benefit. An injectable system offers the potential benefit of minimally invasive release into the myocardium either to restore the injured extracellular matrix or to act as a scaffold for cell delivery. Furthermore, intramyocardial injection of biomaterials and cells has opened new opportunities to explore and also to augment the potentials of this technique to ease morbidity and mortality rates owing to heart failure. This review summarizes the growing body of literature in the field of myocardial tissue engineering, where biomaterial injection, with or without simultaneous cellular delivery, has been pursued to enhance functional and structural outcomes following MI. Additionally, this review also provides a complete outlook on the tissue-engineering therapies presently being used for myocardial regeneration, as well as some perceptivity into the possible issues that may hinder its progress in the future.

Stem cells and injectable hydrogels: Synergistic therapeutics in myocardial repair

“…On the other hand, pure natural materials suffer from uncontrolled compositions and lack suitable mechanical properties. Thus, in order to overcome a deficit of pure materials, synthetic polymers are frequently used in combination with natural polymers or small peptide sequences to promote cell-biomaterial interactions while the structural support is maintained for tissue regeneration (Krupnick et al , 2002, Ravichandran et al , 2012a. For example, collagen or gelatin blended with polyurethane (Stankus et al , 2004), nanofibers of poly(caprolactone) (PCL) (Shin et al , 2004), poly(L-lactide acid) (PLLA) (Krupnick, Kreisel, 2002) or PGS (Ravichandran et al , 2011) improved cellular adhesion and behavior.…”

Heart regeneration after myocardial infarction using synthetic biomaterials

“…Nevertheless, they have not yet reached the cell viability and proliferation rates observed with natural biomaterials. Consequently, synthetic polymers are used in combination with natural compound or small peptide sequences in order to promote cell-biomaterial interactions for tissue regeneration [33].…”

“…On the other hand, NFs need to be attached to the pericardium, so a more invasive administration technique is required. However, it is highly desirable that biomaterials should provide satisfactory mechanical support to the infarcted heart, in order to favor functional recovery of the damaged organ [33]. In this sense, NFs have proved to be able to contribute more efficiently to the heart's mechanical properties than other DDS.…”

Biomimetic materials design for cardiac tissue regeneration

“…Among the potential delivery methods for cardiomyocyte transplantation, direct injection and the use of cardiac tissue patches are two of the most commonly studied approaches. Direct injection of either pluripotent cells or mature cardiomyocytes has been reviewed in detail and assessed by a number of groups as a surgically less‐invasive means for physically introducing regenerative cells at a diseased site . However, direct injection reduces the viability of injected cells, with only 1–32% surviving after transplantation .…”