Specific Scaffolds Developed for Cardiac Tissue Engineering

For cardiac tissue engineering, the ideal scaffolds should consider mixtures of different polymers to achieve the following properties: (1) high porosity (large interconnected pores) to facilitate mass transport; (2) bioadhesiveness to enhance cell attachment; (3) structural stability to withstand both static and dynamic in-vitro cultivation; (4) biodegradability to ensure tissue grafting; (5) elasticity to enable the transmission of contractile forces; and (6) conductivity to facilitate electrical stimulation of the constructs. These properties apply to both synthetic polymer scaffolds and blends of natural and synthetic materials, as well as to acellularized natural cardiac tissues.

Leor et al. [46] have shown that cardiomyocyte seeding within porous alginate scaffolds yield 3D high-density cardiac constructs with a uniform cell distribution. As an alternative to seeding the cells on a preformed scaffold, Zimmermann et al. utilized Matrigelâ„¢ or Matrigelâ„¢ mixed with collagen to generate scaffolds that were uniformly populated with cells [93, 121]. A static sponge scaffold with open interconnected pores, composed of poly(dl-lactide-co-caprolactone), PLGA, and type I collagen demonstrated stable cardiomyocyte growth, a higher expression of cardiac markers, and better contractile properties than sponge scaffolds composed of either collagen or PLGA [13]. This typical example highlights the fact that, for cardiac tissue engineering, a mixture of polymers is preferred to an individual compound in order to generate scaffolds with several of the above-mentioned properties. The electrospinning of a mixture ofbiodegradable PLA- and PGA-based PLGA to generate porous, nanofibrous scaffolds was used to culture primary cardiomyocytes and generate cardiac tissue-like constructs. This indicated that the structure and function of these engineered cardiac tissue scaffolds can be modulated by the chemistry and geometry ofthe nano- and micro-textured surfaces [55]. Most recently, PANi - an electrical conductive polymer - was blended with a natural protein, gelatin, and co-electrospun into conductive, biocompatible nanofibers as cardiac tissue engineering scaffolds to support the attachment and proliferation of cardiac myoblasts [35]. Pedrotty et al. [20] cultured myoblasts on 3D PGA porous scaffolds and reported increased cell proliferation caused by electrical stimulation, or by a culture medium that had been conditioned by mature cardiomyocytes.

Tissue-engineered or acellularized heart valves have already been implanted in pigs [122]. In this approach, acellular scaffolds from heart valves offer unique advantages over synthetic polymers for cardiac valve engineering applications because they retain biologically active ECM molecules to support cellular ingrowth [123]. As a caveat, Rieder et al. [124] examined the immune response of acellularized porcine and human heart valves by measuring the migratory response of human monocytes, and identified species-selective immune reactions. Thus, caution is required in choosing the appropriate heart tissue for acellularization.

Another technique recently considered in cardiac tissue engineering which may accelerate and optimize engineered myocardial assembly is that of "organ printing" [125-127]. This uses a commercially available ink jet printer-like device, which overlays polymers by a "printing" methodology on a template of desired pattern/organization; in this way layers of different thickness are deposited one on top of another to generate homogeneous/heterogeneous scaffolds. Thereafter, the 3D structure is generated by printing, layer-by-layer, a rapidly solidifying thermoreversible gel containing cells in a fashion analogous to multiple layer printing on paper. Time will tell whether computer-aided, jet-based 3D tissue engineering of a living patch of human cardiac muscle is indeed a promising approach for the manufacture of large numbers of functional tissue equivalents in vitro and in vivo.

In considering pharmaceutical applications of cardiac constructs for the HTS of novel drugs to treat cardiomyopathies, arrhythmias, cardiac heart failure and myocardial infarction, there is a clear lack of suitable in-vitro cardiac tissue models. The future technology for cardiovascular tissue engineering for implantation and/ or pharmaceutical application will combine integrative approaches of intelligent scaffolds with human stem cells. The latter will most probably be engineered to secrete a variety of growth factors required for the integration of heart tissue, and represent a combination of biomaterial, tissue engineering, cell therapy, gene therapy, and cardiology.

0 0

Post a comment