Department of Chemical Engineering, McGill University, Montreal, Canada.
Laboratoire d'Ingénierie de Surface, Centre de Recherche sur les Matériaux Avancés, Département de Génie des Mines, de la Métallurgie et des Matériaux, Université Laval, Québec, Canada.
PLoS One. 2022 Aug 30;17(8):e0269316. doi: 10.1371/journal.pone.0269316. eCollection 2022.
Maximizing the re-endothelialization of vascular implants such as prostheses or stents has the potential to significantly improve their long-term performance. Endothelial progenitor cell capture stents with surface-immobilized antibodies show significantly improved endothelialization in the clinic. However, most current antibody-based stent surface modification strategies rely on antibody adsorption or direct conjugation via amino or carboxyl groups which leads to poor control over antibody surface concentration and/or molecular orientation, and ultimately bioavailability for cell capture. Here, we assess the utility of a bioaffinity-based surface modification strategy to immobilize antibodies targeting endothelial cell surface antigens. A cysteine-tagged truncated protein G polypeptide containing three Fc-binding domains was conjugated onto aminated polystyrene substrates via a bi-functional linking arm, followed by antibody immobilization. Different IgG antibodies were successfully immobilized on the protein G-modified surfaces. Covalent grafting of the protein G polypeptide was more effective than surface adsorption in immobilizing antibodies at high density based on fluorophore-labeled secondary antibody detection, as well as endothelial colony-forming cell capture through anti-CD144 antibodies. This work presents a potential avenue for enhancing the performance of cell capture strategies by using covalent grafting of protein G polypeptides to immobilize IgG antibodies.
最大限度地提高血管植入物(如假体或支架)的再内皮化能力有可能显著改善其长期性能。表面固定有抗体的内皮祖细胞捕获支架在临床上显示出明显改善的内皮化。然而,大多数当前基于抗体的支架表面修饰策略依赖于通过氨基或羧基基团的抗体吸附或直接缀合,这导致对抗体表面浓度和/或分子取向的控制不佳,最终影响细胞捕获的生物利用度。在这里,我们评估了一种基于生物亲和性的表面修饰策略用于固定针对内皮细胞表面抗原的抗体的效用。含有三个 Fc 结合结构域的半胱氨酸标记的截断蛋白 G 多肽通过双功能连接臂连接到氨基化聚苯乙烯基质上,然后进行抗体固定。不同的 IgG 抗体成功地固定在蛋白 G 修饰的表面上。基于荧光标记的二级抗体检测以及通过抗-CD144 抗体捕获内皮集落形成细胞,蛋白 G 多肽的共价接枝比表面吸附更有效地将抗体固定在高浓度下。这项工作为通过使用蛋白 G 多肽的共价接枝来固定 IgG 抗体来增强细胞捕获策略的性能提供了一种潜在途径。