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Engineered Protein Coatings to Improve the Osseointegration of Dental and Orthopaedic Implants

机译:工程蛋白涂层可改善牙科和整形外科植入物的骨整合

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摘要

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 hours, 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.
机译:在这里,我们介绍一种经过工程改造的弹性蛋白样蛋白(ELP)的设计,该蛋白经过化学修饰,可以通过新颖的光交联和溶液处理步骤在钛基牙科和整形外科植入物的表面上形成稳定的涂层。 ELP包括扩展的RGD序列(可赋予生物信号)和弹性蛋白样序列(可增强机械稳定性)。 ELP薄膜使用可扩展的旋涂和浸涂工艺在cp-Ti和Ti6Al4V表面上制造,并通过卡宾插入机制进行光敏共价交联。涂层经受了模仿牙螺钉和髋关节置换柄植入的程序,这是临床翻译的关键指标。他们促进了MG63成骨细胞样细胞的快速粘附,24小时后粘附率超过80%,而未涂覆的Ti6Al4V粘附率为38%。与未涂覆的Ti6Al4V相比,MG63细胞在ELP涂层上产生了更多的矿化作用。人骨髓间充质干细胞(hMSCs)的碱性磷酸酶活性较早增加,表明在粘合性ELP涂层上成骨细胞的分化和矿物质沉积更快。大鼠胫骨和股骨的体内研究表明,细胞粘附的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涂层能承受外科手术植入并促进快速骨整合,从而能够更早地植入植入物并潜在地防止微动,从而导致无菌性松动和植入物过早失效。

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