Cardiac tissue engineering: use of a collagen scaffold and bone marrow-derived stem cells in a model of acute and chronic myocardial infarction

1. Cardiopatch in a model of Acute Myocardial Injury (AMI) In this research project we tested the possibility of using a new biodegradable collagen-based material in vivo at cardiac level. We chose the rat as animal model and the acute necrotizing injury (ANI) as type of lesion. Wistar rats of 200-250 grams were used. After anaesthesia, animals were intubated and ventilated mechanically with room air. The heart was exposed through a left thoracotomy and a left ventricular acute necrotizing injury (ANI, freeze-thaw procedure) was created by three sequential exposures (60 s each, 20 s of non-freezing interval) of a liquid nitrogen-cooled cryoprobe (a stainless-steel cylinder, 8mm of diameter). The potential of collagen scaffold (Cardiopatch) for attracting angiogenesis/arteriogenesis was studied in vivo by implantation on a healthy (group 2) or cryoinjured left ventricle (group 3) of rats up to 60 days postinjury times. Blood vessel content and extra-vascular cell infiltration were evaluated within the Cardiopatches, the cryoinjury zones, and the "border zones" of the myocardium facing the cryoinjury zones. In vitro, this biomaterial supported differentiation of cardiomyocytes, smooth muscle and endothelial cells. When implanted in the peritoneum, the scaffold induced a striking neoangiogenesis but also an innate immune response with an abundant macrophage infiltrate and some foreign body giant cells. In the heart, cardiopatches were almost completely absorbed in 60 days and became populated by new arterioles and capillaries in both intact and cryoinjured heart (arterioles in cryoinjury vs. intact zone were about 2,3-fold higher; capillaries in cryoinjury vs. intact zone were 1.7-fold higher). In turn, cardiopatches exerted a "trophic" effect on the organizing granulation tissue that emerged from the wound healing process increasing vessel density of this tissue of 2.7-fold for arterioles and 4-fold for capillaries. Interstitial cells in cardiopatches rarely (