Lai Po-Hong, Chang Yen, Chen Sung-Ching, Wang Chung-Chi, Liang Huang-Chien, Chang Wei-Chun, Sung Hsing-Wen
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
Tissue Eng. 2006 Sep;12(9):2499-508. doi: 10.1089/ten.2006.12.2499.
It was found in our previous study that acellular tissues derived from bovine pericardia consist primarily of insoluble collagen, elastin, and tightly bound glycosaminoglycans (GAGs). It is speculated that the inherent GAGs in acellular tissues may serve as a reservoir for loading basic fibroblast growth factor (bFGF) and promote angiogenesis and tissue regeneration. This study was therefore designed to investigate effects of the content of GAGs in acellular bovine pericardia 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. To control the content of GAGs, acellular tissues were treated additionally with hyaluronidase for 1 (Hase-D1), 3 (Hase-D3), or 5 days (Hase-D5). The in vitro results indicated that a higher content of GAGs in the 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 obtained at 1 week postoperatively showed that the density and the depth of neo-vessels infiltrated into the acellular tissue loaded with bFGF (acellular/bFGF) were significantly greater than the other test samples. At 1 month postoperatively, vascularized neo-connective tissues were found to fill the pores within each test sample, particularly for the acellular/bFGF tissue. These results suggested that the sustained release of bFGF from the acellular/ bFGF tissue continued to be effective in enhancing angiogenesis and generation of new tissues. In conclusion, the inherent GAGs present in acellular tissues may be used for binding and sustained release of bFGF to enhance angiogenesis and tissue regeneration.
我们先前的研究发现,源自牛心包的脱细胞组织主要由不溶性胶原蛋白、弹性蛋白和紧密结合的糖胺聚糖(GAGs)组成。据推测,脱细胞组织中固有的GAGs可能作为装载碱性成纤维细胞生长因子(bFGF)的储存库,并促进血管生成和组织再生。因此,本研究旨在研究脱细胞牛心包中GAGs含量对bFGF结合及其体外释放曲线的影响,同时在大鼠模型中皮下评估其对体内血管生成和组织再生的刺激作用。为了控制GAGs的含量,脱细胞组织额外用透明质酸酶处理1天(Hase-D1)、3天(Hase-D3)或(Hase-D5)5天。体外结果表明,脱细胞组织中较高的GAGs含量导致bFGF结合增加,并且生长因子的释放更加缓慢和持续。术后1周获得的体内结果表明,浸润到装载bFGF的脱细胞组织(脱细胞/bFGF)中的新血管密度和深度明显大于其他测试样品。术后1个月,发现血管化的新结缔组织填充每个测试样品内的孔隙,特别是脱细胞/bFGF组织。这些结果表明,bFGF从脱细胞/bFGF组织中的持续释放继续有效地增强血管生成和新组织的生成。总之,脱细胞组织中存在的固有GAGs可用于bFGF的结合和持续释放,以增强血管生成和组织再生。