Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University Munich, Marchioninistr. 27, 81377, Munich, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
Tissue Eng Regen Med. 2021 Apr;18(2):297-303. doi: 10.1007/s13770-020-00325-w. Epub 2021 Jan 30.
To improve the biocompatibility of porous polyethylene (PPE) implants and expand their application range for reconstructive surgery in poorly vascularized environments, implants were coated with tumor necrosis factor α (TNFα) inhibitor Etanercept. While approved for systemic application, local application of the drug is a novel experimental approach. Microvascular and mechanical integration as well as parameters of inflammation were analyzed in vivo.
PPE implants were coated with Etanercept and extracellular matrix (ECM) components prior to implantation into dorsal skinfold chambers of C57BL/6 mice. Fluorescence microscopy analyses of angiogenesis and local inflammatory response were thrice performed in vivo over a period of 14 days to assess tissue integration and biocompatibility. Uncoated implants and ECM-coated implants served as controls.
TNFα inhibition with Etanercept led to a reduced local inflammatory response: leukocyte-endothelial cell adherence was significantly lowered compared to both control groups (n = 6/group) on days 3 and 14, where the lowest values were reached: 3573.88 leukocytes/mm-2 ± 880.16 (uncoated implants) vs. 3939.09 mm-2 ± 623.34 (Matrigel only) vs. 637.98 mm-2 + 176.85 (Matrigel and Etanercept). Implant-coating with Matrigel alone and Matrigel and Etanercept led to significantly higher vessel densities 7 and 14 days vs. 3 days after implantation and compared to uncoated implants. Mechanical implant integration as measured by dynamic breaking strength did not differ after 14 days.
Our data show a reduced local inflammatory response to PPE implants after immunomodulatory coating with Etanercept in vivo, suggesting improved biocompatibility. Application of this tissue engineering approach is therefore warranted in models of a compromised host environment.
为了提高多孔聚乙烯（PPE）植入物的生物相容性，并扩大其在血管化不良环境下进行重建手术的应用范围，将肿瘤坏死因子α（TNFα）抑制剂依那西普（Etanercept）涂覆在植入物上。虽然该药物已获准用于全身应用，但局部应用是一种新的实验方法。本研究分析了植入物的微血管和机械整合以及炎症参数。
将 Etanercept 和细胞外基质（ECM）成分涂覆在 PPE 植入物上，然后将其植入 C57BL/6 小鼠的背部皮瓣室中。在 14 天的时间内，通过荧光显微镜分析体内的血管生成和局部炎症反应，以评估组织整合和生物相容性。未涂覆的植入物和涂覆 ECM 的植入物作为对照。
Etanercept 抑制 TNFα 导致局部炎症反应减少：与对照组相比，白细胞-内皮细胞黏附在第 3 天和第 14 天显著降低（每组 n=6），最低值分别为：3573.88 个白细胞/mm-2±880.16（未涂覆的植入物）vs.3939.09/mm-2±623.34（仅 Matrigel）vs.637.98/mm-2+176.85（Matrigel 和 Etanercept）。单独用 Matrigel 或 Matrigel 和 Etanercept 涂覆植入物可显著提高植入后 7 天和 14 天的血管密度，并与未涂覆的植入物相比。14 天后，动态断裂强度测量的机械植入物整合没有差异。
我们的数据表明，体内用依那西普进行免疫调节涂层后，PPE 植入物的局部炎症反应降低，提示生物相容性提高。因此，在宿主环境受损的模型中，这种组织工程方法的应用是合理的。
