Ibrahim Mohamed, Bond Jennifer, Medina Manuel A, Chen Lei, Quiles Carlos, Kokosis George, Bashirov Latif, Klitzman Bruce, Levinson Howard
Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University School of Medicine, Durham NC.
Department of Burn Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Eur J Plast Surg. 2017 Nov;40(5):383-392. doi: 10.1007/s00238-017-1308-9. Epub 2017 Apr 28.
Implanted biomaterials are subject to a significant reaction from the host, known as the foreign body response (FBR). We quantified the FBR to five materials following subcutaneous implantation in mice.
Polyvinyl alcohol (PVA) and silicone sheets are considered highly biocompatible biomaterials and were cut into 8mm-diameter disks. Expanded PTFE (ePTFE)and polypropylene are also widely used biocompatible biomaterials and were cut into 2cm-long cylinders. Cotton was selected as a negative control material that would invoke an intense FBR, was cut into disks and implanted. The implants were inserted subcutaneously into female C57BL/6 mice. On post-implantation days 14, 30, 60, 90 and 180, implants were retrieved. Cellularity was assessed with DAPI stain, collagen with Masson's trichrome stain. mast cells with toluidine-blue, macrophages with F4/80 immunohistochemical-stain, and capsular thickness and foreign body giant cells with hematoxylin & eosin.
DAPI revealed a significantly increased cellularity in both PVA andsilicone, and ePTFE had the lowest cell density. Silicone showed the lowest cellularity at d14 and d90 whereas ePTFE showed the lowest cellularity at days 30, 60, and 180. Masson's trichrome staining demonstrated no apparent difference in collagen. Toluidine blue showed no differences in mast cells. There were, however, fewer macrophages associated with ePTFE. On d14, PVA had highest number of macrophages, whereas polypropylene had the highest number at all time points after d14. Giant cells increased earlier and gradually decreased later. On d90, PVA exhibited a significantly increased number of giant cells compared to polypropylene and silicone. Silicone consistently formed the thinnest capsule throughout all time points. On d14, cotton had formed the thickest capsule. On d30 polypropylenehas formed thickest capsule and on days 60, 90 and 180, PVA had formed thickest capsule.
These data reveal differences in capsule thickness and cellular response in an implant-related manor, indicating that fibrotic reactions to biomaterials are implant specific and should be carefully considered when performing studies on fibrosis when biomaterials are being used.
植入的生物材料会受到宿主的显著反应,即异物反应(FBR)。我们对小鼠皮下植入的五种材料的异物反应进行了量化。
聚乙烯醇(PVA)和硅树脂片被认为是高度生物相容性的生物材料,被切成直径8毫米的圆盘。膨化聚四氟乙烯(ePTFE)和聚丙烯也是广泛使用的生物相容性生物材料,被切成2厘米长的圆柱体。棉花被选为会引发强烈异物反应的阴性对照材料,被切成圆盘并植入。将植入物皮下植入雌性C57BL/6小鼠体内。在植入后第14、30、60、90和180天,取出植入物。用DAPI染色评估细胞密度,用Masson三色染色评估胶原蛋白,用甲苯胺蓝评估肥大细胞,用F4/80免疫组织化学染色评估巨噬细胞,用苏木精和伊红评估包膜厚度和异物巨细胞。
DAPI显示PVA和硅树脂中的细胞密度显著增加,而ePTFE的细胞密度最低。硅树脂在第14天和第90天的细胞密度最低,而ePTFE在第30、60和180天的细胞密度最低。Masson三色染色显示胶原蛋白无明显差异。甲苯胺蓝显示肥大细胞无差异。然而,与ePTFE相关的巨噬细胞较少。在第14天,PVA的巨噬细胞数量最多,而聚丙烯在第14天后的所有时间点巨噬细胞数量最多。巨细胞早期增加,随后逐渐减少。在第90天,与聚丙烯和硅树脂相比,PVA的巨细胞数量显著增加。在所有时间点,硅树脂始终形成最薄的包膜。在第14天,棉花形成了最厚的包膜。在第30天,聚丙烯形成了最厚的包膜,在第60、90和180天,PVA形成了最厚的包膜。
这些数据揭示了植入相关情况下包膜厚度和细胞反应的差异,表明对生物材料的纤维化反应具有植入物特异性,在使用生物材料进行纤维化研究时应仔细考虑。