**Acknowledgements**

Another left ventricular restraint proposed is Acorn Corcap, a polyester mesh that is also being assessed in clinical trials after the positive results obtained in animal models [220]. 5 years after implantation it exhibited safety, a sustained reverse remodeling with a significant reduction in the left ventricular end diastolic volume and a slight increase in the sphericity index [221]. However, in an echocardiographic study using tissue velocity imaging, no improvement in

Limited results obtained with the ventricular restraint therapy can be, among other reasons, because of the absence of tissue regeneration. A more advanced approach combines the ventricular restraint therapy with a regenerative strategy such as patches or scaffolds loaded with cells. For instance, the Acorn Corcap and a collagen matrix loaded with MSC has been implanted in sheeps, and the combination was found to limit the fibrosis produced as foreign body reaction against the Corcap and improve the systolic and diastolic function [223].

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

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‐

cardiac output was achieved [222].

302 Regenerative Medicine and Tissue Engineering

**7. Concluding remarks**

cells with other elements.

The authors acknowledge the support of the FP7 NMP3-SL-2009-229239 project ''Regeneration of cardiac tissue assisted by bioactive implants (RECATABI)''.
