Abstract
Clinically, adult human myocardium lacks the possibility of regeneration after myocardial infarction. This results in a progressive loss of functional myocardium and a successive reduction in cardiac performance. Non-living synthetic materials have been widely used to repair myocardial defects; however, material-related failures do occur. In the study, an acellular bovine pericardium with a porous structure fixed by genipin (the AGP patch) was prepared and employed to repair a surgically created myocardial defect in the right ventricle of a rat model. A commercially available expanded polytetrafluoroethylene (e-PTFE) patch was used as a control. At retrieval, a computerized mapping system was employed to acquire local epicardial electrograms of each implanted sample and the appearance of each retrieved sample was grossly examined. The retrieved samples were then processed for histological examinations. The amplitude of local electrograms on the AGP patch increased significantly with increasing the implantation duration, while only low-amplitude electrograms were observed on the e-PTFE patch throughout the entire course of the study. No aneurysmal dilation of the implanted patches was seen for both studied groups. Additionally, no tissue adhesion was observed on the outer (epicardial) surface of the AGP patch, while a moderate tissue adhesion was observed on the e-PTFE patch. On the inner (endocardial) surface, intimal thickening was observed for both studied groups; however, no thrombus formation was found. Intact layers of endothelial and mesothelial cells were identified on the inner and outer surfaces of the AGP patch, respectively. At 4-week postoperatively, smooth muscle cells together with neo-muscle fibers (with a few neo-collagen fibrils), neo-glycosaminoglycans, and neo-capillaries were observed to fill the pores in the AGP patch, an indication of tissue regeneration. These observations were more pronounced at 12-week postoperatively. In contrast, no apparent tissue regeneration was observed in the e-PTFE patch. In summary, the AGP patch may preserve the structure of the right ventricle and prevent aneurysmal dilation while providing the potential for tissue regeneration. These results indicated that the AGP patch holds promise to become a suitable patch for surgical repair of myocardial defects. However, cardiomyocytes were not found within the AGP patch, a limitation of the study. To overcome this problem, syngenic rat bone-marrow derived mesenchymal stem cells (MSCs) were seeded onto the AGP patch (the MSC-seeded AGP patch) and implanted in the same animal model. After seeding MSCs onto the AGP patch, the cells had an uniform and viable fibroblast-like morphology and revealed a good interconnectivity. At retrieval, all the gross and histological observations were similar to those seen in the AGP patch, with the exception of the following phenomenon. Cardiomyocytes, stained positively by troponin T and myosin heavy chain, were observed in the MSC-seeded AGP patch, while the AGP patch was negatively stained. Additionally, MSCs induced angiogenesis in the MSC-seeded AGP patch. In conclusion, cardiomyocytes together with neo-muscle fibers were observed in the MSC-seeded AGP patch, an indication of myocardial tissue regeneration. The MSC-seeded AGP patch may permit the construction of myocardial defects.