Fibrin Glue Alone and Skeletal Myoblasts in a Fibrin Scaffold Preserve Cardiac Function after Myocardial Infarction

Abstract

Current efforts in cardiac tissue engineering center around the use of scaffolds that deliver cells to the epicardial surface. In this study, we examined the effects of fibrin glue as an injectable scaffold and wall support in ischemic myocardium. The left coronary artery of rats was occluded for 17 min, followed by reperfusion. Echocardiography was performed 8 days after infarction. One to 2 days later, either 0.5% bovine serum albumin (BSA) in phosphate-buffered saline, fibrin glue alone, skeletal myoblasts alone, or skeletal myoblasts in fibrin glue were injected into the ischemic left ventricle. Echocardiography was again performed 5 weeks after injection. The animals were then sacrificed and the hearts were fresh frozen and sectioned for histology and immunohistochemistry. Both the fractional shortening (FS) and infarct wall thickness of the BSA group decreased significantly after 5 weeks (p = 0.0005 and 0.02, respectively). In contrast, both measurements for the fibrin glue group, cells group, and cells in fibrin glue group did not change significantly (FS: p = 0.18, 0.89, and 0.19, respectively; wall thickness: p = 0.40, 0.44, 0.43, respectively). Fibrin glue is capable of preserving infarct wall thickness and cardiac function after a myocardial infarction in rats and may be useful as a biomaterial scaffold for myocardial cell transplantation.

Injectable Acellular Hydrogels for Cardiac Repair

“…Christman et al pioneered the field of acellular injectable biomaterials by exploring the effects of fibrin glue as a bulking agent [18,23,34,48]. Fibrin has natural binding domains for soluble growth factors and cellular integrin receptors, motivating its use for wound healing applications.…”

“…Fibrin has natural binding domains for soluble growth factors and cellular integrin receptors, motivating its use for wound healing applications. Although fibrin is commonly utilized for these biological properties, it can also be used as a mechanical support for the myocardium [18,29,34,48]. Specifically, fibrin forms a crosslinked 3-D hydrogel in the myocardium upon injection with a dual-barreled syringe.…”

“…Specifically, fibrin forms a crosslinked 3-D hydrogel in the myocardium upon injection with a dual-barreled syringe. One barrel contains fibrinogen and aprotinin, a fibrinolysis inhibitor, and the second barrel contains thrombin, factor XIIIa, and CaCl 2 [18,23,29,48]. Following a similar mechanism to that involved in the normal clotting cascade in vivo, when fibrinogen and thrombin are mixed, fibrinogen is converted to fibrin which self-assembles and is crosslinked via the factor XIIIa.…”

“…Echocardiograph and explant data showed that fibrin is capable of maintaining fractional shortening (FS) and preserving infarct scar thickness after the material was resorbed [18]. In later studies, using the same model, Christman et al demonstrated the ability of fibrin to substantially decrease infarct size and increase arteriole density in the infarct area compared to control BSA injections [48].…”

“…However, these approaches are limited by the invasive procedure in which they are applied, and clinical adoption has not occurred. In order to circumvent the invasive surgical placement of restraining devices early post-MI, our group and others have begun to explore the use of injectable materials, and specifically hydrogels, to limit infarct expansion and normalize the regional stress distribution [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”