Gelatin microspheres encapsulated with a nonpeptide angiogenic agent, ginsenoside Rg1, for intramyocardial injection in a rat model with infarcted myocardium.

Angiogenic therapies may need to select a stable agent to be delivered. In the study, a nonpeptide angiogenic agent, ginsenoside Rg(1) (Rg(1)), was encapsulated in the gelatin microspheres (MSs) crosslinked with genipin and intramuscularly injected into a rat model with infarcted myocardium. bFGF was used as a control. After swelling in an aqueous environment, the MSs without crosslinking became collapsed and stuck together. For those crosslinked, the swollen MSs appeared to be more stable with an increasing the degree of crosslinking. After it was released from MSs in vitro, the remaining activity of bFGF on HUVEC proliferation reduced significantly, while that of Rg(1) remained constant. An inspection of the retrieved hearts revealed a large aneurysmal left ventricle (LV) with a thinned myocardium and a significant myocardial fibrosis for that treated with the Empty MSs (without drug encapsulation). However, those receiving the MSs encapsulated with bFGF or Rg(1) attenuated the enlargement of the LV cavity and the development of myocardial fibrosis. The densities of microvessels found in the border zones of the infarct treated with the bFGF or Rg(1) MSs were significantly greater than that treated with the Empty MSs. These results indicated that Rg(1), a stable angiogenic agent, successfully enhanced the myocardial perfusion and preserved the infarcted LV function.

Porous acellular bovine pericardia seeded with mesenchymal stem cells as a patch to repair a myocardial defect in a syngeneic rat model.

A patch is often mandatory to repair myocardial defects; however, currently available patches lack the possibility of regeneration. To overcome this limitation, a porous acellular bovine pericardium seeded with BrdU-labeled mesenchymal stem cells (MSCs) was prepared (the MSC patch) to repair a surgically created myocardial defect in the right ventricle of a syngeneic rat model. The bovine pericardium before cell extraction was used as a control (the Control patch). The implanted samples were retrieved at 4- and 12-week postoperatively (n=5 per group at each time point). At retrieval, no aneurysmal dilation of the implanted patches was seen for both studied groups. No apparent tissue adhesion was observed for the MSC patch throughout the entire course of the study, while for the Control patch, two out of the five studied animals at 12-week postoperatively had a filmy adhesion to the chest wall. 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 (epicardial) surfaces of the MSC patch. Smooth muscle cells together with neo-muscle fibers, neo-glycosaminoglycans and neo-capillaries were observed within the pores of the MSC patch. Some cardiomyocytes, which stained positively for BrdU and alpha-sacromeric actin, were observed in the MSC patch, indicating that the implanted MSCs can engraft and differentiate into cardiomyocytes. Additionally, a normality of the local electrograms on the epicardial surface of the MSC patch was observed. In contrast, no apparent tissue regeneration was observed for the Control patch throughout the entire course of the study, while only abnormal electrogram signals were seen on its epicardial surface. In conclusion, the MSC patch may preserve the structure of the ventricular wall while providing the potential for myocardial tissue regeneration.

Tissue regeneration observed in a porous acellular bovine pericardium used to repair a myocardial defect in the right ventricle of a rat model.

OBJECTIVE: Nonliving synthetic materials have been widely used to repair myocardial defects; however, material-related failures do occur. To overcome these problems, an acellular bovine pericardium with a porous structure fixed with genipin (the AGP patch) was developed. METHODS: The AGP patch was used 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 used 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 histologic examination. RESULTS: The amplitude of local electrograms on the AGP patch increased significantly with increasing implantation duration, whereas 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 either studied group. Additionally, no tissue adhesion was observed on the outer (epicardial) surface of the AGP patch, whereas 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 weeks postoperatively, smooth muscle cells, together with neomuscle fibers (with a few neocollagen fibrils), neoglycosaminoglycans, and neocapillaries, were observed to fill the pores in the AGP patch, an indication of tissue regeneration. These observations were more pronounced at 12 weeks postoperatively. In contrast, no apparent tissue regeneration was observed in the e-PTFE patch. CONCLUSION: The present study indicated that the AGP patch holds promise to become a suitable patch for surgical repair of myocardial defects.