Regeneration of Cardiac Tissue Assisted by Bioactive Implants


RECATABI


Small Collaborative Project


NMP-2008-2.3-1 Advanced implants and bioactive materials for critical organs


Name of co-ordinator: Prof. Carlos E. Semino

Partner No. Organisation name Short name Country
1 Institut Quinic de Sarria, Universitat Ramon Llull Fundació Privada, Barcelona IQS-URL ES
2 Fraunhofer Institute for Cell Therapy & Immunology, Leipzig FRAUNHOFER DE
3 Universidad Politécnica de Valencia, Valencia UPVLC ES
4 CREASPINE CREA FR
5 Institut de Recerca de l'Hospital Santa Creu i Sant Pau, Barcelona IR-HSCSP ES
6 Association CARDIO-MONDE, Laboratory of Biosurgical Research, Paris CARDIO-MONDE ASSOC FR



Scientific and Technical Quality

Concept and Objectives

Heart failure is the end-stage of many cardiovascular diseases, but the leading cause is the presence of a large scar due acute to myocardial infarction. Acute myocardial infarction remains a major life-threatening disease for both men and women all over the world and normally happens when blood supply to the heart is interrupted. This is most commonly caused by a surgery. Therapeutic strategies that limit adverse postichemic remodelling in heart failure may prevent ventricular dilatation and maintain the structural support necessary for effective cardiomyocyte contraction. Adverse post ischemic remodelling is related with mitral valve regurgitation, end-stage heart failure and death. Current treatments under development consist in cellular cardiomyoplasty where myocardial cells or stem cells are implanted alone or encapsulated in natural scaffolds (collagens) and grafted onto infarcted ventricles with the hope that cells will contribute to the generation of new myocardial tissue. This approach seems to have a beneficial effect although it is not completely understood and optimized, yet. Moreover, most of the implanted cells died soon after transplantation partially being to due the fact that the cells could not withstand the mechanical forces they experience in the host tissue. One of the main mechanisms by which stem cell transplantation could bring functional benefits is that the implanted cells should provide a supporting "band-aid"-scaffolding effect, which can limit the spread of the infarcted area, preventing excessive remodelling and dilatation of the ventricle. This mechanism should be enhanced by the application of a "bioactive implant" onto the pathologic cardiac area. Until now complete cardiac tissue function and organ regeneration is not well achieved. Thus, the urgent need of better therapeutic platforms is imminent.

In view of this, we created a small consortium (RECATABI) where our main motivation is to develop a bioengineered platform consisting in obtaining newly designed biodegradable scaffolds (constructs) that will support cell survival and early extracellular instruction. RECATABI is an interdisciplinary group of experts in areas such as material sciences, tissue engineering, stem cell technologies and clinical cardiovascular research. RECATABI will integrate and synergise their capacities in order to obtain a novel clinical platform to regenerate necrotic ischemic tissues after cardiac infarct with a simple one-time patch technology application. The consortium will accomplish this by fabricating nanoscale engineered biomaterials and scaffolds that will match the exact biomechanical and biophysical requirements of the implanted tissue. In addition, the construct may induce rapid vascularization to ensure tissue remodelling and regeneration into a newly functional myocardium. The regenerative capacity of the implants will be assessed in small (rodents) and large (sheep) animal models.

The RECATABI concept: We predict that our platform will promote remodelling of necrotic areas of the injured tissue as well as regeneration of functional cardiac tissue (highlighted in bold). We believe that one-time application of a bioactive implant will have a great impact in the area of cardiac tissue regeneration. On the other hand, basic clinical methodologies will be also developed to ensure the position and the fixation of the patch-implant in the target site of the infarct-damaged tissue. On-line, non-destructive monitoring techniques will be used to follow tissue viability and its evolution.