Improved osteointegration by SEW2871-encapsulated multilayers on micro-structured titanium via macrophages recruitment and immunomodulation

The main task for medical-used titanium researches is to improve the in vivo osteointegration. In addition to mesenchymal stromal cells (MSCs)-osteoblasts lineage, macrophages also undertake irreplaceable roles in the osteointegration process of a titanium implant. The timely recruitment and efficient immunomodulation of macrophages is important. In this work, to firstly endow macrophages recruitment ability and immunomodulation effects to titanium, we fabricated a micro-structured titanium via a double acid etching method. Then a gelatin-chitosan multilayer contained SEW2871 (a macrophage recruitment agent) was constructed on the micro-structured titanium by a layer-by-layer (LBL) self-assembly technique. According to our results, the prepared samples effectively induced macrophages migration when SEW2871 was slowly released. The anti-inflammatory response of macrophages was enhanced and the pro-inflammatory response was alleviated, which were attributed to the changed surface roughness and wettability. This immunomodulation effects of macrophages further improved the osteogenic differentiation of MSCs in vitro and obtained a better osteointegration in vivo after 6 weeks of implantation. Therefore, this study demonstrated that a favorable osteointegration of titanium materials could also be achieved by regulating macrophages recruitment and immunomodulation, which implying a potential strategy for titanium implants amelioration.