Creating the bioartificial myocardium for cardiac repair: challenges and clinical targets

Abstract

The association of stem cells with tissue-engineered scaffolds constitutes an attractive approach for the repair of myocardial tissue with positive effects to avoid ventricular chamber dilatation, which changes from a natural elliptical to spherical shape in heart failure patients. Biohybrid scaffolds using nanomaterials combined with stem cells emerge as new therapeutic tool for the creation of 'bioartificial myocardium' and 'cardiac wrap bioprostheses' for myocardial regeneration and ventricular support. Biohybrids are created introducing stem cells and self-assembling peptide nanofibers inside a porous elastomeric membrane, forming cell niches. Our studies lead to the creation of semi-degradable 'ventricular support bioprostheses' for adaptative LV and/or RV wrapping, designed with the concept of 'helical myocardial bands'. The goal is to restore LV elliptical shape, and contribute to systolic contraction and diastolic filling (suction mechanism). Cardiac wrapping with ventricular bioprostheses may reduce the risk of heart failure progression and the indication for heart transplantation.

Design and Assembly Procedures for Large-Sized Biohybrid Scaffolds as Patches for Myocardial Infarct

“…37 The application of the bioactive implants on ischemic sheep hearts showed enhanced parameters of systolic and diastolic functions in a 6-month trial. The LV chamber dilatation was reversed and infarct size was reduced in treated animals.…”

Development of Bioactive Patch for Maintenance of Implanted Cells at the Myocardial Infarcted Site

“…The benefits reported for cardiomyoplasty lead cells-based therapies to turn into new hope in regenerative medicine and are undergoing experimental and clinical trials. Unfortunately, until now, cell transplantation has not achieved clear hemodynamic benefits for myocardial diseases [22,23]. The main obstacle is that MI is an ischemic event followed by inflammatory reaction, cytokines, and growth factors secretion.…”

“…Therefore, the transplantation of unprotected cells into this environment results in significant cell death and low cell bioretention and engraftment [24]. In this context, it seems suitable to provide a safe environment (niche) for cell proliferation and differentiation [23]. On the other hand, extracellular matrix that gives structural strength to the LV is pathologically modified (collagen type I decreased from 80% to 40%) and a fibrous scar is formed [22].…”

“…The regional structural changes lead to global LV geometric change (dilated cardiomyopathy), altering fiber direction and diminishing function. This contributes to an increase in LV wall stress and mitral valve regurgitation [23].…”

“…Complete biodegradation of grafted scaffolds may compromise long-term limitation of postischemic ventricular remodeling. For this reason, nondegradable poly(ethyl acrylate) (PEA) with cylindrical orthogonal pores and semidegradable poly(caprolactone 2-(methacryloyloxy) ethyl ester) (PCLMA) with interconnected spherical pores) membranes were tested [23]. PEA has mechanical properties in the range of those of soft biological tissues and it has shown excellent biological performance in vitro with different cell types [27][28][29][30][31][32][33].…”