School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104, United States.
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven 5612, Netherlands.
ACS Biomater Sci Eng. 2021 Dec 13;7(12):5611-5621. doi: 10.1021/acsbiomaterials.1c01190. Epub 2021 Nov 12.
Biotin-avidin interactions have been explored for decades as a technique to functionalize biomaterials, as well as for targeting, but whether changes in these interactions can be leveraged for immunomodulation remain unknown. The goal of this study was to investigate how biotin density and avidin variant can be used to deliver the immunomodulatory cytokine, interleukin 4 (IL4), from a porous gelatin scaffold, Gelfoam, to primary human macrophages . Here, we demonstrate that the degree of scaffold biotinylation controlled the binding of two different avidin variants, streptavidin and CaptAvidin. Biotinylated scaffolds were also loaded with streptavidin and biotinylated IL4 under flow, suggesting a potential use for targeting this biomaterial . While biotin-avidin interactions did not appear to influence the protein release in this system, increasing degrees of biotinylation did lead to increased M2-like polarization of primary human macrophages over time , highlighting the capability to leverage biotin-avidin interactions to modulate the macrophage phenotype. These results demonstrate a versatile and modular strategy to impart immunomodulatory activity to biomaterials.
生物素-亲和素相互作用已被探索了数十年，作为一种赋予生物材料功能的技术，以及作为靶向治疗的手段，但这些相互作用的变化是否可以用于免疫调节仍不清楚。本研究的目的是研究生物素密度和亲和素变体如何用于从多孔明胶支架 Gelfoam 向原代人巨噬细胞递送电免疫调节细胞因子白细胞介素 4 (IL4)。在这里，我们证明了支架的生物素化程度控制了两种不同的亲和素变体（链霉亲和素和 CaptAvidin）的结合。生物素化支架也可以在流动条件下加载链霉亲和素和生物素化的白细胞介素 4，这表明这种生物材料具有靶向的潜力。虽然生物素-亲和素相互作用似乎不会影响该系统中的蛋白质释放，但增加的生物素化程度确实导致原代人巨噬细胞随着时间的推移向 M2 样极化增加，这突出了利用生物素-亲和素相互作用来调节巨噬细胞表型的能力。这些结果表明了一种灵活的模块化策略，可以赋予生物材料免疫调节活性。
