Tethered-TGF-β increases extracellular matrix production of vascular smooth muscle cells

Tethered-TGF-β increases extracellular matrix production of vascular smooth muscle cells
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DOI:
10.1016/s0142-9612(00)00196-4
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发表时间:
2001-03-01
期刊:
影响因子:
14
通讯作者:
West, JL
West, JL
中科院分区:
工程技术1区
文献类型:
--
作者:
Mann, BK;Schmedlen, RH;West, JL

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为组织工程和伤口愈合应用开发的生物材料需要支持强大的细胞粘附,但也需要被这些细胞合成的新组织所取代。为了保持组织的机械完整性,细胞必须在支架降解之前产生足够的细胞外基质。我们先前已经表明,含有细胞粘附配体以促进或改善细胞粘附的材料可以减少细胞外基质的产生(Mann et al.用细胞粘附肽修饰表面改变细胞外基质沉积。Biomaterials 1999:20:2281-6)。组织工程支架中细胞的这种减少的基质产生可能导致组织衰竭。然而.我们发现TGF-β 1可用于支架中以显著增加基质产生。在0.04 pmol/ml(1 ng/ml)TGF-β 1存在下,生长在粘附配体修饰的玻璃表面和含有共价结合粘附配体的PEG水凝胶中的血管平滑肌细胞的基质产生增加,TGF-β 1可以抵消这些粘附配体对基质产生的影响;基质产生甚至可以增加到不存在粘附肽时观察到的水平以上。此外,TGF-β 1共价固定到PEG保留了其增加基质产生的能力。将TGF-β 1拴系到聚合物支架上导致基质产量比相同量的可溶性TGF-β 1显著增加。(C)2001爱思唯尔科技有限公司版权所有。
Biomaterials developed for tissue engineering and wound healing applications need to support robust cell adhesion, yet also need to be replaced by new tissue synthesized by those cells. In order to maintain mechanical integrity of the tissue, the cells must generate sufficient extracellular matrix before the scaffold is degraded. We have previously shown that materials containing cell adhesive ligands to promote or improve cell adhesion can decrease extracellular matrix production (Mann et al.. Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition. Biomaterials 1999:20:2281-6). Such decreased matrix production by cells in tissue engineering scaffolds may result in tissue failure. However. we have found that TGF-beta1 can be used in scaffolds to dramatically increase matrix production. Matrix production by vascular smooth muscle cells grown on adhesive ligand-modified glass surfaces and in PEG hydrogels containing covalently bound adhesive ligands was increased in the presence of 0.04 pmol/ml (1 ng/ml) TGF-beta1, TGF-beta1 can counteract the effect of these adhesive ligands on matrix production; matrix production could be increased even above that observed in the absence of adhesive peptides. Further, TGF-beta1 covalently immobilized to PEG retained its ability to increase matrix production. Tethering TGF-beta1 to the polymer scaffold resulted in a significant increase in matrix production over the same amount of soluble TGF-beta1. (C) 2001 Elsevier Science Ltd. All rights reserved.