Acellular Matrix Biomaterial Promotes Vasculogenesis and Cardiac Repair: Evidence of a Bioinductive FGF-2-dependent Mechanism 

Background: Extracellular matrix (ECM) biomaterials can promote cardiac repair and functional recovery post-MI, but the underlying mechanisms remain unclear. ECM has bioinductive effects given its capacity to retain growth... [ view full abstract ]

Background: Extracellular matrix (ECM) biomaterials can promote cardiac repair and functional recovery post-MI, but the underlying mechanisms remain unclear. ECM has bioinductive effects given its capacity to retain growth factors critical to cardiac repair. We explored a bioinductive mechanism through which ECM-biomaterial therapy enhances myocardial repair.

Methods/Results: We compared active-ECM to biologically inactivated-ECM to explore specific bioinductive effects (figure 1). Expression of paracrine angiogenic mediators was compared in relevant in vitro and in vivo models. First, ECM-biomaterial (CorMatrix-ECM) was shown to release FGF-2. To better understand the bioinductive capacity, human cardiac fibroblasts (HuCF) were isolated from atrial appendage. HuCF were seeded onto active (FGF-2 positive) or biologically inactive (glutaraldehyde-fixed; FGF-2 negative) ECM. Conditioned media was analyzed for angiogenic protein expression. HuCF on active-ECM assumed a pro-angiogenic state relative to the inactive-ECM group, showing increased expression of FGF-2 and VEGF (figure 1). FGF-2 inhibition (1M PD173074) attenuated the pro-angiogenic response suggesting a paracrine role for FGF-2. Functional analysis of ECM biomaterial-induced angiogenesis was performed using human endothelial cells embedded in Matrigel. Active-ECM induced greater endothelial tube formation relative to the inactive-ECM group (figure 1). Next, we employed a rat coronary ligation model of MI. Active-ECM was applied over the epicardial surface of the infarct and compared after a 14-week treatment period. Active-ECM enhanced vascularity in infarcted myocardium and was observed adjacent to increased tissue expression of vasculogenic growth factors, namely FGF-2 and VEGF.

Conclusion: Epicardial ECM-biomaterial therapy enhances post-MI functional recovery and repair by an FGF-2-dependent paracrine mechanism that stimulates vasculogenesis.