A novel bioartificial myocardial tissue and its prospective use in cardiac surgery.

Abstract

Congenital heart defects such as atrial septal defect, ventricular septal defect, double outlet ventricles and the hypoplastic left heart syndrome as well as ischemic heart disease are associated with aplastic, defective or necrotic myocardial structures. In many of these instances patch closure, reconstruction of the defect or revascularization is required. We have developed a contractile bioartificial myocardial tissue, which offers new perspectives for various reconstructive surgical interventions, including congenital heart surgery. Neonatal rat cardiomyocytes were seeded in vitro in a commercially available collagen scaffold. Histological examination and ultrastructural evaluation were performed. Protein and mRNA analysis were carried out by two-dimensional electrophoresis and reverse transcription-polymerase chain reaction (RT-PCR). Force measurements of contractions from the spontaneously beating or the pharmacologically stimulated bioartificial myocardial patch were obtained. A solid matrix of 20 x 15 x 2 mm with spontaneous contractions resulted 36 h after cardiomyocyte seeding. Histology showed a tight mesh of collagen fibrils. Two-dimensional electrophoresis and RT-PCR revealed cardiotypical proteins (actin, tropomyosin, creatine kinase, ventricular light chain) and mRNA (myosin heavy chain, Connexin 43). The elasticity curve during passive stretch was similar to that of myocardium. Contractile force increased after topical administration of Ca(2+) and adrenaline. However, stretch led to the highest levels of contractile force. Our novel contractile bioartificial tissue can be engineered in vitro and may open novel avenues for myocardial tissue replacement in congenital and reconstructive heart surgery. From the current standpoint autologous or allogeneic cells would be preferred over xenogeneic sources.