当前位置：
X-MOL 学术
›
ACS Biomater. Sci. Eng.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Collagen-Mimetic Proteins with Tunable Integrin Binding Sites for Vascular Graft Coatings
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2018-06-13 00:00:00 , DOI: 10.1021/acsbiomaterials.8b00070 Juan Felipe Diaz Quiroz 1 , Patricia Diaz Rodriguez 1 , Josh D. Erndt-Marino 1 , Viviana Guiza 1 , Bailey Balouch 1 , Tyler Graf 1 , William M. Reichert 2 , Brooke Russell 3 , Magnus Höök 3 , Mariah S. Hahn 1
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2018-06-13 00:00:00 , DOI: 10.1021/acsbiomaterials.8b00070 Juan Felipe Diaz Quiroz 1 , Patricia Diaz Rodriguez 1 , Josh D. Erndt-Marino 1 , Viviana Guiza 1 , Bailey Balouch 1 , Tyler Graf 1 , William M. Reichert 2 , Brooke Russell 3 , Magnus Höök 3 , Mariah S. Hahn 1
Affiliation
|
Achieving graft endothelialization following implantation continues to be a challenge in the development of “off-the-shelf,” small-caliber, arterial prostheses. Coating grafts with biomolecules to support the retention, migration, and differentiation of adherent endothelial precursor cells (EPCs) is a promising approach toward improving graft endothelialization. Designer Collagen Scl2-2 with 1 integrin binding site per strand (DC2-1X) is a Streptococcus pyogenes-derived, collagen-like protein that has previously been evaluated as a graft coating due to its ability to resist platelet aggregation and to promote attachment and migration of “late outgrowth” EPCs (EOCs). However, these prior assessments were performed in the absence of physiological shear. In addition, although DC2-1X coatings supported increased migration rates relative to native collagen coatings, EOC attachment and spreading remained inferior to collagen controls at all DC2-1X concentrations assayed. Thus, the objectives of the present work were the following: (1) to improve EOC attachment on DC2 coatings by modulating the number and spacing of DC2 integrin binding sites (IBS) and (2) to evaluate the retention, migration, and differentiation of adherent EOCs under physiological shear stress. Using single point mutations, three novel DC2 variants were generated containing either two IBS (DC2-2X) or three IBS (DC2-3X1 and DC2-3X2) per strand. After initial evaluation of the potential of each DC2 variant to support increased EOC attachment relative to DC2-1X, DC2-2X and DC2-3X1 coatings were further assessed under physiological shear for their capacity to promote EOC retention, migration, and differentiation relative to DC2-1X and collagen controls. An increase in the number of IBS from 1 to 3 significantly improved EOC retention on DC2 coatings while also supporting increased average migration rates. Moreover, EOCs on DC2-3X1 coatings showed increased gene-level expression of intermediate endothelial cell differentiation markers relative to collagen. Overall, the current results suggest that DC2-3X1 warrants further investigation as a vascular graft coating.
中文翻译：
具有可调节整合素结合位点的用于血管移植涂层的模拟胶原蛋白
在植入后实现移植内皮化仍然是开发“现成的”小口径动脉假体的挑战。用生物分子包被移植物以支持粘附的内皮前体细胞（EPC）的保留，迁移和分化是改善移植物内皮化的一种有前途的方法。d esigner Ç ollagen Scl2- 2与1整联蛋白结合每链（DC2-1X）位点是酿脓链球菌来源的胶原蛋白样蛋白，由于其抗血小板聚集和促进“晚期生长” EPC（EOC）附着和迁移的能力，先前已被评估为移植涂层。但是，这些先前的评估是在没有生理剪切的情况下进行的。另外，尽管相对于天然胶原涂层，DC2-1X涂层支持增加的迁移速率，但在所有测定的DC2-1X浓度下，EOC附着和散布仍不如胶原蛋白对照。因此，本工作的目标如下：（1）通过调节DC2整联蛋白结合位点（IBS）的数量和间距来改善EOC在DC2涂层上的附着力，以及（2）评价其的保留，迁移和分化。在生理剪切应力下粘附的EOC。使用单点突变，生成了三个新颖的DC2变体，每条链包含两个IBS（DC2-2X）或三个IBS（DC2-3X1和DC2-3X2）。在初步评估每种DC2变体相对于DC2-1X支持增加EOC附着的潜力之后，在生理剪切下进一步评估了DC2-2X和DC2-3X1涂层相对于DC2促进EOC保留，迁移和分化的能力。 -1X和胶原蛋白对照。IBS的数量从1增加到3，可以显着提高DC2涂层的EOC保留率，同时还可以提高平均迁移率。此外，相对于胶原蛋白，DC2-3X1涂层上的EOCs显示中间内皮细胞分化标记物的基因水平表达增加。总体而言，当前结果表明DC2-3X1作为血管移植物涂层值得进一步研究。
更新日期：2018-06-13
中文翻译：
具有可调节整合素结合位点的用于血管移植涂层的模拟胶原蛋白
在植入后实现移植内皮化仍然是开发“现成的”小口径动脉假体的挑战。用生物分子包被移植物以支持粘附的内皮前体细胞（EPC）的保留，迁移和分化是改善移植物内皮化的一种有前途的方法。d esigner Ç ollagen Scl2- 2与1整联蛋白结合每链（DC2-1X）位点是酿脓链球菌来源的胶原蛋白样蛋白，由于其抗血小板聚集和促进“晚期生长” EPC（EOC）附着和迁移的能力，先前已被评估为移植涂层。但是，这些先前的评估是在没有生理剪切的情况下进行的。另外，尽管相对于天然胶原涂层，DC2-1X涂层支持增加的迁移速率，但在所有测定的DC2-1X浓度下，EOC附着和散布仍不如胶原蛋白对照。因此，本工作的目标如下：（1）通过调节DC2整联蛋白结合位点（IBS）的数量和间距来改善EOC在DC2涂层上的附着力，以及（2）评价其的保留，迁移和分化。在生理剪切应力下粘附的EOC。使用单点突变，生成了三个新颖的DC2变体，每条链包含两个IBS（DC2-2X）或三个IBS（DC2-3X1和DC2-3X2）。在初步评估每种DC2变体相对于DC2-1X支持增加EOC附着的潜力之后，在生理剪切下进一步评估了DC2-2X和DC2-3X1涂层相对于DC2促进EOC保留，迁移和分化的能力。 -1X和胶原蛋白对照。IBS的数量从1增加到3，可以显着提高DC2涂层的EOC保留率，同时还可以提高平均迁移率。此外，相对于胶原蛋白，DC2-3X1涂层上的EOCs显示中间内皮细胞分化标记物的基因水平表达增加。总体而言，当前结果表明DC2-3X1作为血管移植物涂层值得进一步研究。
京公网安备 11010802027423号