Study on the potential mechanism of anti-inflammatory activity of covalently immobilized hyaluronan and heparin
Study on the potential mechanism of anti-inflammatory activity of covalently immobilized hyaluronan and heparin
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DOI：
10.1002/jbm.a.36885
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发表时间：
2020-01-29
影响因子：
4.9
通讯作者：
Groth, Thomas
中科院分区：
文献类型：
--
作者：
AlKhoury, Hala;Hautmann, Adrian;Groth, Thomas
生物材料植入后发生的炎症和随后的纤维化包囊是促进设计新型生物相容性材料以调节免疫应答的努力的问题。在这项研究中，具有抗炎活性的糖胺聚糖（GAG）如透明质酸（HA）和肝素（Hep）使用EDC/NHS交联化学共价结合到NH 2修饰的表面。固定化和物理表面性质，其特征在于通过原子力显微镜，水接触角的研究和流动电位的测量，证明存在的表面上的GAG变得更加亲水性和带负电荷的相比，NH 2-改性。在此使用THP-1衍生的巨噬细胞来研究GAG影响炎症反应的作用机制，所述炎症反应通过研究巨噬细胞粘附、多核巨细胞（MNGC）的形成和在GAG修饰的表面上减少的IL-1 β释放来阐明。通过NF-κ B（p65亚基）的免疫荧光染色和免疫印迹，对与巨噬细胞活化相关的信号转导过程进行了详细的研究。我们还研究了FITC标记的GAG的缔合和易位。结果显示NF-κ B水平以及巨噬细胞与HA和Hep结合并摄取HA和Hep的能力显著降低。这些结果表明，GAG的抗炎活性不仅与使表面更具亲水性有关，而且还与其积极参与与炎症反应相关的信号转导过程有关，这可能为设计用于可植入生物医学设备的新型抗炎表面涂层铺平道路。
Inflammation and subsequent fibrotic encapsulation that occur after implantation of biomaterials are issues that fostered efforts in designing novel biocompatible materials to modulate the immune response. In this study, glycosaminoglycans (GAG) like hyaluronic acid (HA) and heparin (Hep) that possess anti-inflammatory activity were covalently bound to NH2-modified surfaces using EDC/NHS cross-linking chemistry. Immobilization and physical surface properties were characterized by atomic forces microscopy, water contact angle studies and streaming potential measurements demonstrating the presence of GAG on the surfaces that became more hydrophilic and negatively charged compared to NH2-modified. THP-1 derived macrophages were used here to study the mechanism of action of GAG to affect the inflammatory responses illuminated by studying macrophage adhesion, the formation of multinucleated giant cells (MNGCs) and IL-1 beta release that were reduced on GAG-modified surfaces. Detailed investigation of the signal transduction processes related to macrophage activation was performed by immunofluorescence staining of NF-kappa B (p65 subunit) together with immunoblotting. We studied also association and translocation of FITC-labeled GAG. The results show a significant decrease in NF-kappa B level as well as the ability of macrophages to associate with and take up HA and Hep. These results illustrate that the anti-inflammatory activity of GAG is not only related to making surfaces more hydrophilic, but also their active involvement in signal transduction processes related to inflammatory reactions, which may pave the way to design new anti-inflammatory surface coatings for implantable biomedical devices.