Biomaterial adherent macrophage apoptosis is increased by hydrophilic and anionic substrates in vivo

An in vivo rat cage implant system was used to identify potential surface chemistries that prevent failure of implanted biomedical devices and prostheses by limiting monocyte adhesion and macrophage fusion into foreign-body giant cells while inducing adherent-macrophage apoptosis. Hydrophobic, hydrophilic, anionic, and cationic surfaces were used for implantation. Analysis of the exudate surrounding the materials revealed no differences between surfaces in the types or levels of cells present. Conversely, the proportion of adherent cells undergoing apoptosis was increased significantly on anionic and hydrophilic surfaces (46 ± 3.7 and 57 ± 5.0%, respectively) when compared with the polyethylene terephthalate base surface. Additionally, hydrophilic and anionic substrates provided decreased rates of monocyte/macrophage adhesion and fusion. These studies demonstrate that biomaterial-adherent cells undergo material-dependent apoptosis in vivo, rendering potentially harmful macrophages nonfunctional while the surrounding environment of the implant remains unaffected.

本研究采用大鼠皮下笼内植入体内实验系统，旨在筛选可防止医用植入器械及假体失效的潜在表面化学组成：通过抑制单核细胞黏附、巨噬细胞融合为异物巨细胞，同时诱导黏附巨噬细胞凋亡。实验中分别使用疏水、亲水、阴离子及阳离子表面材料开展植入实验。对材料周围渗出液的分析结果显示，不同表面材料对应的细胞类型及细胞水平均无显著差异。与之相反，与聚对苯二甲酸乙二酯基底表面相比，阴离子及亲水表面上发生凋亡的黏附细胞占比显著升高，分别为(46±3.7)%及(57±5.0)%。此外，亲水及阴离子基底可降低单核细胞/巨噬细胞的黏附与融合速率。本研究证实，黏附于生物材料的细胞会发生材料依赖性的体内凋亡，可使具有潜在危害的巨噬细胞失活，同时不会对植入物周围的微环境造成影响。