A surgical-repair material is commonly required to prevent postsurgical adhesions. In study I, the genipin-fixed acellular bovine pericardial tissue (the AGP patch) was used as a surgical-repair material to fix an abdominal wall defect created in a rat model. The results show that the AGP patch was free of any adhesions to the visceral organs at 3-month postoperatively. Histological findings revealed that a neo-peritoneum (homogeneous and composed of organized vascularized connective tissues covered by an intact layer of mesothelial cells) was observed on the inner surface of the AGP patch. Hence, the lack of formation of intra-abdominal adhesions for the AGP patch at 3-month postoperatively observed in this study may be caused by the regeneration of a neo-mesothelial layer on its peritoneal surface.
However, one animal had a filmy adhesion to the bowel at 1-month postoperatively. These observations may be attributed to the incompletion of remesothelialization that was caused by a lack of angiogenesis in the regenerated tissue observed at 1-month postoperatively. Therefore, a novel angiogenic factor-Ginsenoside Rg1 (Rg1) was applied to solve these problems. Additionally, to form a larger pores with increased interconnectivity within the tissue matrix, the acellular bovine pericardium was further treated with acetic acid and subsequently with collagenase (the porous acellular tissue). A tissue-engineering ECM is generally accepted to have to be highly porous for blood invasion to occur in vivo and to enable oxygen and nutrients to be supplied to cells.
In study II, the porous acellular tissue additionally loaded with Rg1 (the Acellular/Rg1 patch) was used as a surgical-repair material to fix a defect created in the pericardium of a rabbit model. At 3-month postoperatively, an intact layer of neo-mesothelial cells (in which remesothelialization was complete), was already present on top of the neo-connective tissue fibrils regenerated in the outer (the lung side) and inner (the epicardial side) surfaces of the Acellular/Rg1 patch. These cells was only observed in part of the outer surface of the Acellular patch. These results demonstrated that in the presence of Rg1, remesothelialization on each side of the Acellular/Rg1 patch was faster.
As mentioned in study II, the primary challenge for tissue engineering is to develop a vascular supply that can support the metabolic needs of the engineered tissue. The glycosaminoglycans (GAGs) that remained in the acellular bovine pericardia are speculated to have served as a reservoir for loading basic fibroblast growth factor (bFGF) and promote angiogenesis and tissue regeneration. Therefore, the study III was designed to investigate the effects of the content of GAGs that remains in the porous acellular tissues on the binding of bFGF and its release profile in vitro, while its stimulation in angiogenesis and tissue regeneration in vivo were evaluated subcutaneously in a rat model.
The in vitro results indicated that a higher content of GAGs remained in the porous acellular tissue resulted in an increase in bFGF binding and in a more gradual and sustained release of the growth factor. The in vivo results revealed that the density of neo-microvessels together with neo-connective tissue fibrils infiltrated into the porous acellular tissue loaded with bFGF (the Acellular/bFGF patch) markedly exceeded that of other hyaluronidase-treated test samples. These results suggested that the sustained release of bFGF from the Acellular/bFGF patch continued effectively to enhance angiogenesis and generation of new tissues. Based on these results, the feasibility of using this material in myocardial tissue engineering was evaluated.
In a clinical context, cardiac repair by surgical patching is currently limited by the inability to promote local tissue regeneration within the implanted materials. In study IV, a bFGF-loaded porous bovine pericardium populated with BrdU-labeled mesenchymal stem cells (MSCs) was used as a patch (the bFGF/MSC patch) to repair a myocardial defect created in a syngeneic rat model. At retrieval, newly regenerated muscle fibers, GAGs, smooth muscle cells and microvessels were seen in the middle layers of all studied groups, indicating tissue regeneration, especially in the bFGF/MSC patch. Moreover, BrdU-labeled cardiomyocytes, SMCs and endothelial cells were identified in the bFGF/MSC patch, while no cardiomyocytes were observed in the other patches. These results provided evidence of myocardial tissue regeneration within the bFGF/MSC patch through a process that involves cell recruitment and tissue-specific differentiation.

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