INSERM UMR1121 "Biomaterials and Bioengineering", 11 Rue Humann, 67085 Strasbourg, France.
Politecnico di Torino, Corso duca degli Abruzzi 24, 10129 Torino, Italy.
Mater Sci Eng C Mater Biol Appl. 2020 Jul;112:110845. doi: 10.1016/j.msec.2020.110845. Epub 2020 Mar 13.
In order to create a stable interface with the host tissue, porous implants are widely used to ensure the in-growth of the cells and the colonization of the implant. An ideal porous implant should have a 3D architecture that enables fast migration of incoming cells while not inducing a significant pro-inflammatory response by the immune cells. Moreover, in patients where the healing is impeded (patients with co-morbidities and metabolic diseases), porosity by itself is not enough for fast colonization, and the surface properties of the implant should also be controlled. In this study, we present a controlled oxidation-based surface treatment of microbead-based porous titanium implants which not only increases the colonization by connective tissue cells but also decreases the macrophage attachment. The treatment created a nanotextured surface on the implants with an acidic shift of isoelectric point (from 4.09 to 3.09) without endangering implant's mechanical integrity. The attachment and metabolic activity of activated macrophages were significantly lower on treated surfaces with an increase in the secretion of anti-inflammatory IL-1RA and a decrease in pro-fibrotic CCL-18. Human fibroblasts proliferated faster on the treated surfaces over 14 days with near complete colonization of the whole thickness of the implant with an accompanying an increase in the secretion of TGF-beta. The surface treated samples demonstrated partial filling of the entire pores. We demonstrated that the use of nanoscale surface treatments that can be applied to the whole internal surface of porous titanium implants can significantly alter both the immune response and the colonization of the implants and can be used to fine-tune and personalize implant interfaces according to patient needs.
为了与宿主组织形成稳定的界面，广泛使用多孔植入物来确保细胞的向内生长和植入物的定植。理想的多孔植入物应具有 3D 结构，使进入的细胞能够快速迁移，而不会引起免疫细胞的显著炎症反应。此外，在愈合受到阻碍的患者（患有合并症和代谢疾病的患者）中，孔隙率本身不足以快速定植，植入物的表面特性也应得到控制。在这项研究中，我们提出了一种基于受控氧化的微珠多孔钛植入物表面处理方法，该方法不仅增加了结缔组织细胞的定植，而且还减少了巨噬细胞的附着。该处理方法在植入物表面形成了纳米结构，等电点从 4.09 变为 3.09，同时不损害植入物的机械完整性。处理后的表面上，活化的巨噬细胞的附着和代谢活性显著降低，同时抗炎因子 IL-1RA 的分泌增加，促纤维化因子 CCL-18 的分泌减少。经过 14 天的培养，人成纤维细胞在处理后的表面上增殖更快，整个植入物的厚度几乎完全被细胞覆盖，同时 TGF-β的分泌也增加。经过表面处理的样本显示出整个孔的部分填充。我们证明，使用可以应用于多孔钛植入物整个内部表面的纳米级表面处理方法，可以显著改变免疫反应和植入物的定植，并可根据患者的需求对植入物界面进行微调并实现个性化。
