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纤维蛋白微珠(FMB)作为用于培养细胞和加速伤口愈合的可生物降解载体。

Fibrin microbeads (FMB) as biodegradable carriers for culturing cells and for accelerating wound healing.

作者信息

Gorodetsky R, Clark R A, An J, Gailit J, Levdansky L, Vexler A, Berman E, Marx G

机构信息

Sharett Institute of Oncology, Hadassah University Hospital, Jerusalem, Israel.

出版信息

J Invest Dermatol. 1999 Jun;112(6):866-72. doi: 10.1046/j.1523-1747.1999.00600.x.

Abstract

We have developed biodegradable fibrin-derived microbeads as potent cell carriers. The fibrin-derived microbeads, 50-200 microm in diameter, were tested for their attachment to a wide range of cell types. Fibrin-derived microbeads were shown to be greatly haptotactic to cells (such as endothelial cells, smooth muscle cells and fibroblasts), which respond to fibrinogen in contrast to keratinocytes and different cell lines derived from leukocytic lineage. The cells on fibrin-derived microbeads could be maintained for more than 10 d and achieved a high density. 31P-nuclear magnetic resonance was employed to monitor phosphate metabolism in cells, with densities on the order of 100 million cells per g of fibrin-derived microbeads. The 31P-nuclear magnetic resonance adenosine triphosphate and phosphocreatine signals, equivalent to the signal obtained with perfused normal skin, indicated that metabolism of cells on fibrin-derived microbeads was responsive to oxygenation and nutrients. Light, fluorescent, and confocal laser microscopy revealed that the porous fibrin-derived microbeads accommodate up to 200-300 cells due to their high surface area which minimized contact inhibition. Cells could degrade the fibrin-derived microbeads and be transferred to seed culture flasks without trypsinization. In a pig skin wound healing model, fibrin-derived microbeads + fibroblasts were transplanted into full thickness punch wounds. This procedure was compared with other treatment modalities, such as the addition of human platelet-derived growth factor BB or fibrin-derived microbeads alone. By the third day after wounding, only the wounds in which fibroblasts on fibrin-derived microbeads were added showed significant formation of granulation tissue. Based on the above, we project many uses of our novel fibrin-derived microbead technology for cell culturing, wound healing and tissue engineering.

摘要

我们已开发出可生物降解的纤维蛋白衍生微珠作为有效的细胞载体。对直径为50 - 200微米的纤维蛋白衍生微珠进行了测试,以考察它们对多种细胞类型的附着情况。结果表明,纤维蛋白衍生微珠对细胞(如内皮细胞、平滑肌细胞和成纤维细胞)具有很强的趋触性,这些细胞对纤维蛋白原产生反应,而角质形成细胞和源自白细胞谱系的不同细胞系则不然。纤维蛋白衍生微珠上的细胞能够维持10天以上并达到高密度。采用31P核磁共振来监测细胞中的磷酸盐代谢,每克纤维蛋白衍生微珠上的细胞密度约为1亿个。31P核磁共振的三磷酸腺苷和磷酸肌酸信号与灌注正常皮肤所获得的信号相当,表明纤维蛋白衍生微珠上细胞的代谢对氧合作用和营养物质有反应。光学、荧光和共聚焦激光显微镜显示,多孔的纤维蛋白衍生微珠由于其高表面积可容纳多达200 - 300个细胞,从而将接触抑制降至最低。细胞能够降解纤维蛋白衍生微珠,并且无需胰蛋白酶消化即可转移至种子培养瓶中。在猪皮肤伤口愈合模型中,将纤维蛋白衍生微珠 + 成纤维细胞移植到全层打孔伤口中。将该程序与其他治疗方式进行比较,如添加人血小板衍生生长因子BB或单独使用纤维蛋白衍生微珠。受伤后第三天,只有添加了纤维蛋白衍生微珠上的成纤维细胞的伤口显示出明显的肉芽组织形成。基于以上研究,我们预计我们新型的纤维蛋白衍生微珠技术在细胞培养、伤口愈合和组织工程方面有多种用途。

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