Institute of Biomaterials and Biomedical Engineering (IBBME) and the Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada; Equipe de Recherche sur les Relations Matrice Extracellulaire-Cellules (ERRMECe), Institut des Matériaux, Maison International de la Recherche, Université de Cergy-Pontoise, 95000 Neuville sur Oise, France.
Institute of Biomaterials and Biomedical Engineering (IBBME) and the Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
Acta Biomater. 2018 Jan 15;66:129-140. doi: 10.1016/j.actbio.2017.11.013. Epub 2017 Nov 8.
Monocyte interactions with materials that are biofunctionalized with fibronectin (Fn) are of interest because of the documented literature which associates this protein with white blood cell function at implant sites. A degradable-polar hydrophobic ionic polyurethane (D-PHI), has been reported to promote an anti-inflammatory response from human monocytes. The aim of the current work was to study the influence of intrinsic D-PHI material chemistry on Fn adsorption (mono and multi-layer structures), and to investigate the influence of such chemistry on the structural state of the Fn, as well as the latter's influence on the activity of human monocytes on the protein coated substrates. Significant differences in Fn adsorption, surface hydrophobicity and the availability of defined peptide sequences (N terminal, C terminal or Cell Binding Domain) for the Fn in mono vs multilayer structures were observed as a function of the changes in intrinsic material chemistry. A D-PHI-formulated polyurethane substrate with subtle changes in anionic and hydrophobic domain content relative to the polar non-ionic urethane/carbonate groups within the polymer matrix promoted the lowest activation of monocytes, in the presence of multi-layer Fn constructs. These results highlight the importance of chemical heterogeneity as a design parameter for biomaterial surfaces, and establishes a desired strategy for controlling human monocyte activity at the surface of devices, when these are coated with multi-layer Fn structures. The latter is an important step towards functionalizing the materials with multi-layer protein drug carriers as interventional therapeutic agents.
The control of the behavior of monocytes, especially migration and activation, is of crucial interest to modulate the inflammatory response at the site of implanted biomaterial. Several studies report the influence of adsorbed serum proteins on the behavior of monocytes on biomaterials. However, few studies show the influence of surface chemical group distribution on the controlled adsorption and the subsequent induced conformation- of mono versus multi-layer assembled structures generated from specific proteins implicated in wound repair. The current research considered the role of Fn adsorption and conformation in thin films while interacting with the intrinsic chemistry of segmented block polyurethanes; and the influence of the former on modulation and activation of human monocytes.
由于文献记录表明这种蛋白质与植入部位的白细胞功能有关，因此人们对用纤维连接蛋白（Fn）生物功能化的材料与单核细胞的相互作用很感兴趣。已报道可生物降解的极性疏水性离子型聚氨酯（D-PHI）可促进人单核细胞的抗炎反应。目前工作的目的是研究内在的 D-PHI 材料化学对 Fn 吸附（单分子和多分子层结构）的影响，并研究这种化学对 Fn 结构状态的影响，以及后者对涂覆蛋白质的基底上人类单核细胞活性的影响。结果发现，与聚合物基质中的极性非离子型氨酯/碳酸酯基团相比，D-PHI 配方的聚氨酯基质中的阴离子和疏水性结构域的含量发生变化时，Fn 在单分子和多分子层结构中的吸附、表面疏水性以及 Fn 上特定肽序列（N 端、C 端或细胞结合结构域）的可用性都有显著差异。在多分子层 Fn 结构存在的情况下，与聚合物基质中的极性非离子型氨酯/碳酸酯基团相比，D-PHI 配方的聚氨酯基质中阴离子和疏水性结构域的含量发生变化时，Fn 以多层结构形式吸附时，可促进单核细胞的最低激活。这些结果强调了化学不均匀性作为生物材料表面设计参数的重要性，并为在多层 Fn 结构涂覆的装置表面控制人类单核细胞活性建立了一种理想的策略。后者是用多层蛋白质药物载体作为介入治疗剂对材料进行功能化的重要步骤。
控制单核细胞的行为，尤其是迁移和激活，对于调节植入生物材料部位的炎症反应至关重要。有几项研究报告了吸附的血清蛋白对生物材料上单核细胞行为的影响。然而，很少有研究表明表面化学基团分布对特定蛋白质组装的单分子层和多分子层结构的吸附和随后诱导的构象的控制作用，这些蛋白质与伤口修复有关。目前的研究考虑了 Fn 在与分段嵌段型聚氨酯的固有化学相互作用时的吸附和构象，以及前者对人类单核细胞的调制和激活的影响。
