Yeo Giselle C, Santos Miguel, Kondyurin Alexey, Liskova Jana, Weiss Anthony S, Bilek Marcela M M
The Heart Research Institute, 7 Eliza Street, Newtown, New South Wales 2050, Australia.
Institute of Physiology, Academy of Sciences of the Czech Republic, Národní 1009/3, Prague 14220, Czech Republic.
ACS Biomater Sci Eng. 2016 Apr 11;2(4):662-676. doi: 10.1021/acsbiomaterials.6b00049. Epub 2016 Mar 8.
The mechanical strength, durability, corrosion resistance, and biocompatibility of metal alloys based on zirconium (Zr) and titanium (Ti) make them desirable materials for orthopedic implants. However, as bioinert metals, they do not actively promote bone formation and integration. Here we report a plasma coating process for improving integration of such metal implants with local bone tissue. The coating is a stable carbon-based plasma polymer layer that increased surface wettability by 28%, improved surface elasticity to the range exhibited by natural bone, and additionally covalently bound the extracellular matrix protein, tropoelastin, in an active conformation. The thus biofunctionalized material was significantly more resistant to medical-grade sterilization by steam, autoclaving or gamma-ray irradiation, retaining >60% of the adhered tropoelastin molecules and preserving full bioactivity. The interface of the coating and metal was robust so as to resist delamination during surgical insertion and in vivo deployment, and the plasma process employed was utilized to also coat the complex 3D geometries typical of orthopedic implants. Osteoblast-like osteosarcoma cells cultured on the biofunctionalized Zr surface exhibited a significant 30% increase in adhesion and up to 70% improvement in proliferation. Cells on these materials also showed significant early stage up-regulation of bone marker expression (alkaline phosphatase, 1.8 fold; osteocalcin, 1.4 fold), and sustained up-regulation of these genes (alkaline phosphatase, 1.3 fold; osteocalcin, 1.2 fold) in osteogenic conditions. In addition, alkaline phosphatase production significantly increased (2-fold) on the functionalized surfaces, whereas bone mineral deposition increased by 30% above background levels compared to bare Zr. These findings have the potential to be readily translated to the development of improved Zr and Ti-based implants for accelerated bone repair.
基于锆(Zr)和钛(Ti)的金属合金的机械强度、耐久性、耐腐蚀性和生物相容性使其成为骨科植入物的理想材料。然而,作为生物惰性金属,它们不会积极促进骨形成和整合。在此,我们报告一种等离子体涂层工艺,用于改善此类金属植入物与局部骨组织的整合。该涂层是一种稳定的碳基等离子体聚合物层,可使表面润湿性提高28%,将表面弹性改善至天然骨所呈现的范围,并额外以活性构象共价结合细胞外基质蛋白原弹性蛋白。如此生物功能化的材料对蒸汽、高压灭菌或伽马射线辐照等医用级消毒具有显著更高的耐受性,保留了>60%的黏附原弹性蛋白分子并保持完全的生物活性。涂层与金属的界面坚固,以抵抗手术植入和体内部署过程中的分层,并且所采用的等离子体工艺还用于涂覆骨科植入物典型的复杂三维几何形状。在生物功能化的Zr表面培养的成骨样骨肉瘤细胞的黏附显著增加30%,增殖最多提高70%。这些材料上的细胞在成骨条件下还显示出骨标志物表达的显著早期上调(碱性磷酸酶,1.8倍;骨钙素,1.4倍),以及这些基因的持续上调(碱性磷酸酶,1.3倍;骨钙素,1.2倍)。此外,在功能化表面上碱性磷酸酶的产生显著增加(2倍),而与裸露的Zr相比,骨矿物质沉积比背景水平增加了30%。这些发现有可能很容易转化为用于加速骨修复的改良Zr和Ti基植入物的开发。