Engineered protein coatings to improve the osseointegration of dental and orthopaedic implants.
Engineered protein coatings to improve the osseointegration of dental and orthopaedic implants.
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DOI：
10.1016/j.biomaterials.2015.12.030
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发表时间：
2016-03
期刊：
影响因子：
14
通讯作者：
Heilshorn SC
中科院分区：
文献类型：
--
作者：
Raphel J;Karlsson J;Galli S;Wennerberg A;Lindsay C;Haugh MG;Pajarinen J;Goodman SB;Jimbo R;Andersson M;Heilshorn SC
在这里，我们提出了一种工程类弹性蛋白（ELP）的设计，该蛋白经过化学修饰，可通过新颖的光交联和溶液处理步骤在钛基牙科和骨科植入物的表面上形成稳定的涂层。 ELP 包括用于提供生物信号的扩展 RGD 序列和用于机械稳定性的类弹性蛋白序列。使用可扩展的旋涂和浸涂工艺在 cp-Ti 和 Ti6Al4V 表面上制造 ELP 薄膜，并通过卡宾插入机制进行光活性共价交联。这些涂层能够承受模拟牙科螺钉和髋关节置换柄植入的程序，这是临床转化的一个关键指标。它们促进 MG63 成骨细胞样细胞的快速粘附，24 小时后粘附率超过 80%，而未涂层 Ti6Al4V 的粘附率为 38%。与未涂层的 Ti6Al4V 相比，MG63 电池在 ELP 涂层上产生的矿化明显更多。人骨髓间充质干细胞 (hMSC) 的碱性磷酸酶活性较早增加，表明成骨分化和粘附 ELP 涂层上的矿物质沉积更快。大鼠胫骨和股骨体内研究表明，细胞粘附 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 涂层可承受手术植入并促进快速骨整合，从而实现更早的种植体加载，并可能防止导致无菌性松动和过早种植体失败的微移动。
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.