Raphel Jordan, Karlsson Johan, Galli Silvia, Wennerberg Ann, Lindsay Christopher, Haugh Matthew G, Pajarinen Jukka, Goodman Stuart B, Jimbo Ryo, Andersson Martin, Heilshorn Sarah C
Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Biomaterials. 2016 Mar;83:269-82. doi: 10.1016/j.biomaterials.2015.12.030. Epub 2016 Jan 6.
Here we present the design of an engineered, elastin-like protein (ELP) that is chemically modified to enable stable coatings on the surfaces of titanium-based dental and orthopaedic implants by novel photocrosslinking and solution processing steps. The ELP includes an extended RGD sequence to confer bio-signaling and an elastin-like sequence for mechanical stability. ELP thin films were fabricated on cp-Ti and Ti6Al4V surfaces using scalable spin and dip coating processes with photoactive covalent crosslinking through a carbene insertion mechanism. The coatings withstood procedures mimicking dental screw and hip replacement stem implantations, a key metric for clinical translation. They promoted rapid adhesion of MG63 osteoblast-like cells, with over 80% adhesion after 24 h, compared to 38% adhesion on uncoated Ti6Al4V. MG63 cells produced significantly more mineralization on ELP coatings compared to uncoated Ti6Al4V. Human bone marrow mesenchymal stem cells (hMSCs) had an earlier increase in alkaline phosphatase activity, indicating more rapid osteogenic differentiation and mineral deposition on adhesive ELP coatings. Rat tibia and femur in vivo studies demonstrated that cell-adhesive ELP-coated implants increased bone-implant contact area and interfacial strength after one week. These results suggest that ELP coatings withstand surgical implantation and promote rapid osseointegration, enabling earlier implant loading and potentially preventing micromotion that leads to aseptic loosening and premature implant failure.
在此,我们展示了一种经过工程改造的类弹性蛋白(ELP)的设计,该蛋白经过化学修饰,通过新颖的光交联和溶液处理步骤,能够在钛基牙科和骨科植入物表面形成稳定的涂层。ELP包含一个延长的RGD序列以赋予生物信号传导功能,以及一个类弹性蛋白序列以实现机械稳定性。使用可扩展的旋涂和浸涂工艺,通过卡宾插入机制进行光活性共价交联,在纯钛(cp-Ti)和Ti6Al4V表面制备了ELP薄膜。这些涂层经受住了模拟牙科螺钉和髋关节置换柄植入的程序,这是临床转化的关键指标。它们促进了MG63成骨样细胞的快速黏附,24小时后黏附率超过80%,相比之下,未涂层的Ti6Al4V上的黏附率为38%。与未涂层的Ti6Al4V相比,MG63细胞在ELP涂层上产生了显著更多的矿化。人骨髓间充质干细胞(hMSCs)的碱性磷酸酶活性更早增加,表明在具有黏附性的ELP涂层上成骨分化和矿物质沉积更快。大鼠胫骨和股骨的体内研究表明,细胞黏附性的ELP涂层植入物在一周后增加了骨-植入物接触面积和界面强度。这些结果表明,ELP涂层能够经受手术植入并促进快速骨整合,从而能够更早加载植入物,并有可能防止导致无菌性松动和植入物过早失效的微动。