Abstract 2893: Fibronectin-Hepatocyte Growth Factor Enhances Reconstruction of Myocardium in a Tissue-Engineered Cardiac Patch Derived from Extracellular Matrix
Introduction Urinary bladder matrix (UBM) promotes myocardial repair when used as a full-thickness cardiac patch, but regeneration is incomplete. The present study combined UBM with Fibronectin-Hepatocyte Growth Factor (FnHGF). Fibronectin allows HGF to bind to UBM for longer residence time. We hypothesize that FnHGF will alter the profile of cells that populate the remodeled UBM cardiac patch and enhance cardiac function.
Methods UBM treated with FnHGF was implanted into the porcine right ventricular wall (F group) to repair a surgically created defect. Nontreated UBM patches (U group) and Dacron patches (D group) served as controls (N=5/group). Electromechanical mapping (NOGA system) was performed at 60 days after surgery. Linear local shortening (LLS) was used to assess regional contractility, and electrical activity was recorded. Histological examinations and RTPCR were performed to assess the presence of myocardial cells and capillary density. Data is reported as mean ± SD. * indicate p<0.05 versus (ANOVA with post-hoc test).
Results The LLS was significantly improved in F group (0.51 ± 1.57 %) compared with controls (U: -1.06 ± 1.84, D: -2.72 ± 2.59 %)*, while they were inferior to the normal myocardium (13.7 ± 4.3 %)*. Mean electrical activity was 1.49 ± 0.82 mV in F group, which was statistically greater than control groups (U: 0.93 ± 0.71 mV, D: 0.30 ± 0.22 mV)*, and less than the normal myocardium (8.24 ± 2.49 mV)*. Within the patch-implanted region, the F Group showed an endocardial endothelial monolayer. The healed wound tissue contained predominantly α-smooth muscle actin positive cells (likely myofibroblasts), with the F group showing the thickest layer, and the D group the thinnest. The capillary density was greatest in the F group (31.7 ± 20.0/mm2 *, U group 14.3 ± 10.5/mm2; D group 4.6 ± 4.4/mm2). Rare isolated islands of α-actinin positive cells were observed only in the F group healed wounds, suggesting the presence of cardiomyocytes. The result of RTPCR supported histological findings.
Conclusion The FnHGF-UBM patch demonstrated increased contractility and electrical activity compared to UBM alone or Dacron, and facilitated a homogeneous repopulation of host cells. UBM loaded with FnHGF may contribute to constructive myocardial remodeling.