Construction of a bioengineered cardiac graft

Objectives: Currently available graft materials for repair of congenital he art defects cause significant morbidity and mortality because of their lack of growth potential. An autologous cell seeded graft may improve patient o utcomes, We report our initial experience with the construction of a biodeg radable graft seeded with cultured rat or human cells and identify their 3- dimensional growth characteristics. Methods: Fetal rat ventricular cardiomy ocytes, stomach smooth muscle cells, skin fibroblasts, and adult human atri al and ventricular cardiomyocytes were isolated and cultured in vitro. Thes e cells were injected into or laid onto biodegradable gelatin meshes, and t heir rate of proliferation and spatial location within the mesh was evaluat ed by using a cell counter and, histologic analysis. Results: Rat cardiomyo cytes, smooth muscle cells, and fibroblasts demonstrated steady proliferati on over 3 to 4 weeks. The gelatin mesh was slowly degraded, but this proces s was most rapid after seeding with fibroblasts, Human atrial cardiomyocyte s proliferated within the gelatin meshes but at a slower rate than that of fetal rat cardiomyocytes, Human ventricular cardiomyocytes survived within the gelatin mesh matrix but did not increase in number during the 2-week du ration of evaluation. Grafts seeded with rat ventricular cells exhibited sp ontaneous rhythmic contractility. All cell types preferentially migrated to the uppermost surface of each graft and formed a 300- to 500-mu m thick la yer. Conclusions: Fetal rat ventricular cardiomyocytes, gastric smooth musc le cells, skin fibroblasts, and adult human atrial cardiomyocytes can grow in a 3-dimensional pattern within a biodegradable gelatin mesh. Similar aut ologous cell-seeded constructs may eventually be applied to repair congenit al heart defects.