**7. Concluding remarks**

Several therapeutic strategies have been proposed in the last decade to limit the adverse spread of the ischemic tissue and ventricle dilation or even to generate new myocardial tissue. These treatments consist in cellular therapy (so-called cellular cardiomyoplasty) where cells of different origin are implanted by different techniques onto the infarcted ventricle with the hope that cells will contribute to the generation of new contractile tissue to replace the scar, electrically coupled with the host myocardium. But despite the intense efforts and work put in the field, attempts so far have failed. Most of the implanted cells die soon after transplan‐ tation due to the fact that the cells cannot withstand the mechanical forces they experience in the host tissue. Mechanisms underlying the slight improvements observed are still undeter‐ mined; the paracrine effect is usually considered the way through which cells act, but the precise mechanisms are not completely understood yet. Besides, for this therapeutic approach to evolve to a realistic alternative to conventional treatments, some critical issues are still to be clarified: the way of delivery to maximize cell engraftment and minimize cell loss and death, the ideal cell type to be used, and the optimal time of cell administration (if they are implanted too soon, the inflammatory process kills the implanted cells, but if it is too late, the presence of the fibrotic scar limits their beneficial effects). New strategies already under study envision to improve cell survival by pre-conditioning the cells, pre-treating the host tissue or combining cells with other elements.

A possible way of localizing the appropriate cells in the target diseased tissue is to entrap them in a cell-friendly gelling biomaterial. Besides, gels can incorporate bioactive molecules for their controlled supply, and their preparation procedure (in the case of *in situ* gelling materials) avoids any invasive surgery. The injection of gelly materials alone onto the infarcted myocar‐ dium has shown some beneficial effects by itself and contributes somehow to limit the ventricular remodeling, for their slight role as mechanical support. Combining cells with gelly materials contributes, to some extent, to increase the cells residence time in the site of interest, and enhances cells adhesion and survival by providing them a better microenvironment. However, the consistency of these materials is generally too weak to withstand the synchro‐ nous contraction of the heart muscle without spreading from their target location, and their mechanical properties are too low to reach significant improvements in terms of containment of the dilated ventricle and post-infarct ventricular dysfunction.

Alternative tissue engineering strategies combine cells with three-dimensional scaffolds or patches to host them and improve their survival, induce the formation of new blood vessels and extracellular matrix and at the same time support the native tissue mechanically. The advantages of using myocardial patches or scaffolds are not only their usually superior mechanical properties, but also their wide versatility in terms of chemistries and morphology. There are many fabrication techniques for the preparation of scaffolds, leading to very different architectures, and these options are broadening with the computer-assisted techniques. Generally, positive results have been obtained by using scaffolds. In studies in which the therapeutic efficiency of a material was compared when used as an injectable gel or as a prefabricated scaffold or patch, the scaffold gave better results. When the scaffolds were loaded with growth factors or adhesion motives, in most of the cases the outcome was better. Mechanical and electrical stimulation are of help for cardiomyocytes to mature within the scaffolds and develop the characteristics and structures typical of cardiac tissue. Unfortunate‐ ly, the implantation of epicardiac patches is much more invasive than that of injectable gels, and they need to be vascularized to ensure the success of the graft. Many attempts have addressed these questions but a satisfying solution has not been found yet.
