Nano-Micro-Structured Polymeric Matrices For Engineered Cardiac Prototissues


People involved: Gianfranco B. Fiore, Monica Soncini, Alberto Redaelli, Andrea Pavesi, Filippo Consolo

Funding source: Cariplo Foundation

Grant number: CARIPLO-2008-2459

Funding period: 2009 - 2011

Partners: Universita' degli Studi del Piemonte Orientale "Amedeo Avogadro" (Vercelli).

Cardiovascular diseases, the leading cause of death in western countries, are characterized by the progressive loss of functional cells and the subsequent heart failure. Although great advances in the patient’s life quality have been achieved by means of pharmacological treatments and controlled lifestyle, in most cases organ transplantation is the only possible treatment, which, however, encounters serious limitations due to insufficient organ availability, major surgical procedures, costs and long-term immunosuppression.
Ex vivo tissue engineering, which has been developed as a basic technology for regenerative medicine, complementing the previous experiences of cell and molecular therapies, can be an alternative therapeutic strategy. Central to this approach is the development of matrices able to mimic the microenvironment of the tissues to be substituted, in which stem cells, in the presence of exogenously added bioactive molecules (growth/differentiation factors, adhesive molecules) can be expanded and differentiated towards specific phenotypes.
The aim of the project is the development of novel therapeutic strategies of regenerative medicine with the ultimate goal of obtaining nano and micro-structured matrices for prototissues for engrafting in animal organs experimentally injured. The Biomech Group is mainly involved in the activities related to the manufacturing and setting-up of a perfusion dynamic culture system.
Innovative biocompatible and biodegradable PM, modified with bioactive molecules, will be used to expand and induce to differentiation adult stem cells from adipose tissue (recently assessed as the best autologous source in terms of accessibility and amount). In particular, electroactive polymer, which can be deformed when subjected to a small voltage, so to stimulate the differentiation of stem cells in cardiomyocytes, will be directly electrospun or used as coating of electrospun materials. Stem cells will be co-cultured with growth factor producing cells -such as cardiac fibroblasts- incorporated in microcapsules. Cultures will be carried on in perfusion systems to enhance the nutrient support and thus cell viability in the matrices. Stem cells will be transduced with vectors for the expression of fluorescent proteins, allowing to trace the fate of the cells in vitro and within the engrafted cardiac proto-tissues. The proposed integrated multidisciplinary research project may allow to setup innovative technologies to be exploited for their potential biotechnological and clinical applications.