In situ constructive myocardial remodeling of extracellular matrix patch enhanced with controlled growth factor release

Abstract

Objective: In an effort to expand treatment for advanced heart failure, we sought to develop a tissue-engineered cardiac patch for constructive and functional in situ myocardial regeneration.

Methods: An extracellular matrix patch derived from porcine small intestine submucosa was incorporated with a controlled release of basic fibroblast growth factor. The patch was surgically implanted into the porcine right ventricle (group B, n = 5). Untreated extracellular matrix (group U) and Dacron (group D) patches served as control (n = 5/group). Cardiovascular magnetic resonance was performed in all 3 groups 60 days postsurgery to evaluate regional contractility with peak longitudinal strain, perfusion with relative maximum upslope, and extent of fibrosis/edema with extracellular volume fraction. Electrophysiologic-anatomic mapping was performed in group B. Histology and quantitative reverse transcription-polymerase chain reaction were performed for further tissue characterization.

Results: Cardiovascular magnetic resonance-derived parameters were significantly better in group B compared with groups U and D (strain: group B = -16.6% ± 1.8%, group U = -14.7% ± 1.2%, group D = -9.0% ± 1.5%, P < .001; upslope: group B = 13.7% ± 1.1%, group U = 10.8% ± 1.3%, group D = 6.4% ± 1.8%, P < .001; extracellular volume: group B = 45% ± 7%, group U = 54% ± 10%, group D = 70% ± 10%, P = .003). Histology in group B showed a homogenous distribution of host cells, including tropomyosin and α-sarcomeric actinin-positive maturing cardiomyocytes. Group B demonstrated the greatest degree of vasculogenesis as determined by capillary density analysis (group B = 19.5 ± 6.2/mm(3), group U = 12.7 ± 2.5/mm(3), group D = 6.9 ± 3.7/mm(3), P < .001). Quantitative reverse transcription-polymerase chain reaction supported the histologic findings. Electrophysiologic-anatomic mapping in group B indicated positive electrical conductivity in the patch area.

Conclusions: The extracellular matrix patch enhanced with controlled release of fibroblast growth factor facilitated in situ constructive repopulation of the host cells, including cardiomyocyte and functional regeneration, increased regional contractility and tissue perfusion, and positive electrical activity in a porcine preparation.

Keywords: cardiovascular magnetic resonance imaging; drug delivery system; growth factor; myocardial repair; tissue engineering.