The Study On Collagen Membranes Loaded With Collagen-binding Human Vascular Endothelial Growth Factor Accelerating Healing Of The Injured Rabbit Heart

Scar tissue formation after myocardial infarction (MI) results in an irreversible damage to the cardiac function. Cardiac repair is, therefore, essential to restore function of the heart following MI. Vascular endothelial growth factor (VEGF) is an important active protein for the induction of angiogenesis. It can promote vasodilation in the early stage of MI and angiogenesis latterly, which may play an important role in improving cardiac microenvironment of ischemia and hypoxia. However, potential problems associated with the prolonged and excessive production of VEGF cannot be ignored. Clinical studies of VEGF protein revealed evidence of a dose-dependent effect, high-dose VEGF protein resulted in a better therapeutic effect. Given the side effects of high-level VEGF in the circulation, an increase in the local VEGF level may represent a reasonable treatment for ischemic heart disease.Tissue-engineered myocardial patches could be useful in the repair of myocardial injuries. Traditional biomaterials are usually used as scaffold, which can provide adhesion sites and mechanical support. However, they could not actively guide cells. The modification of the scaffold is needed to increase the repair effect. Modification of the scaffold property to improve the local microenvironment and the addition of active factors such as stem cells or growth factors to the scaffold are mainly involved in current research.The aim of the present study was to evaluate a collagen targeting delivery system for myocardial repair. A specific peptide collagen-binding domain (CBD) was fused to human vascular endothelial growth factor (VEGF) to enhance the binding of VEGF to collagen. In this study, collagen membranes loaded with CBD-VEGF, natural VEGF, or phosphatebuffered saline are used as cardiac patches to repair the infarcted myocardium in a rabbit model. CBD-VEGF/collagen group could effectively induce more cells to penetrate into the collagen membrane after4weeks and promote more vascularization in infarcted myocardium after12weeks compared with the other two control groups. Echocardiography and hemodynamic studies both show cardiac function improvement in the CBDVEGF/collagen group. These results reveal that implantation of CBD-VEGF collagen membrane patch into the infarcted myocardium could effectively improve left ventricle cardiac function and increase the vascular density.