**6.3 Heart**

Left ventricular assist device [LVAD] was developed as mechanical circulatory support [MCS] for heart failure patients. A long-term implantable continuous-flow LVAD named "the Heart II™ left Ventricular Assist system [Abbott Laboratories] has been approved by U.S. Food and Drug Administration for indications of destination therapy and bridging to transplantation. While the technology is advancing to achieve smaller size and eradication of drive lines, the expectation is to apply continuous-flow technology, which is in the experimental phase, to total heart replacement [45].

Implantation of a total artificial heart is indicated in end-stage heart failure patients. Acute hemodynamic restoration and clinical stabilization are achieved and the patient is then bridged to transplantation. It has been reported that a total artificial heart is associated with a post-transplantation survival rate very similar to national survival rates five years after transplantation [46] It has also been reported that total artificial heart patients have high rates of successful bridge-to-transplant and survival on par with biventricular assist device supported patients. The future objectives are decreased device size, continuous flow mechanisms, and use of bioprosthetic materials. Overcoming these hurdles will provide increased device longevity and decreased post-implant complications [47].

Taylor and associates have claimed that engineering a bioartificial heart has become a possibility. They have proposed a novel type of in vivo organ engineering utilizing pre-clinical models where decellularized hearts are heterotopically transplanted. The aim was to harness the capability of the body at least partly to repopulate the scaffold. The authors have added load and electric input and have posited that vascular and parenchymal cell maturation can occur. The authors have implanted porcine decellularized hearts acutely and chronically in living recipients in a heterotopic position and have demonstrated that short-term implantation promotes endothelial cell adhesion to the vessel lumens and that long-term implantation also promotes tissue formation with evidence of cardiomyocytes and endothelial cells present within the graft [48].

Pelletier et al. have reported that Rein-Heart-total artificial heart had shown safe and effective function in vivo and in vitro testing. The Rein-Heart has effectively replaced the native hearts' functions in animals for up to two days [49].

There are obstacles to overcome before obtaining a bioartificial heart. These obstacles are, achieving adequate durability, longer than five years, minimizing thromboemboli and hemolysis, better efficiency, maintaining pulmonary-systemic circulatory balance and reduced size to accommodate in women and small adolescents and children [50].

#### **6.4 Lung**

The structure of the lung is complex and lung decellularization is a complex process. The information is not sufficient. The most suitable cell types, media, and growth factors and how to provide the optimal conditions of ventilation, perfusion and oxygenation along the process of biofabrication are issues to be studied for further progress.

The key problem in producing a bioengineered lung is how to drive stem cell differentiation onto the different cell phenotypes. The role played by physical stimuli is also important in lung bioengineering because the cells within the organ are physiologically subjected to two main stimuli. These stimuli are ventilation and blood perfusion across the organ [51].

Extracorporeal membrane oxygenation and mechanical can be used temporarily as a bridge to transplantation. Experimental transplantation of bioartificial lung developed by perfusion decellularized synthetic scaffolds has been shown to provide gas exchange in vivo over a long period. The present level of achievements reveals that obtaining a transplantable artificial lung is not possible soon [52].
