Department of Orthopaedic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110055, P.R. China.
Engineering Research Center of High Entropy Alloy Materials (Liaoning Province), School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, P.R. China.
ACS Appl Mater Interfaces. 2024 Jan 24;16(3):3171-3186. doi: 10.1021/acsami.3c16459. Epub 2024 Jan 11.
Biomaterial scaffolds, including bone substitutes, have evolved from being primarily a biologically passive structural element to one in which material properties such as surface topography and chemistry actively direct bone regeneration by influencing stem cells and the immune microenvironment. Ti-6Al-4V(Ti6Al4V) implants, with a significantly higher elastic modulus than human bone, may lead to stress shielding, necessitating improved stability at the bone-titanium alloy implant interface. Ti-24Nb-4Zr-8Sn (Ti2448), a low elastic modulus β-type titanium alloy devoid of potentially toxic elements, was utilized in this study. We employed 3D printing technology to fabricate a porous scaffold structure to further decrease the structural stiffness of the implant to approximate that of cancellous bone. Microarc oxidation (MAO) surface modification technology is then employed to create a microporous structure and a hydrophilic oxide ceramic layer on the surface and interior of the scaffold. In vitro studies demonstrated that MAO treatment enhances the proliferation, adhesion, and osteogenesis capabilities on the scaffold surface. The chemical composition of the MAO-Ti2448 oxide layer is found to enhance the transcription and expression of osteogenic genes in bone mesenchymal stem cells (BMSCs), potentially related to the enrichment of NbO and SnO in the oxide layer. The MAO-Ti2448 scaffold, with its synergistic surface activity and low stiffness, significantly activates the anti-inflammatory macrophage phenotype, creating an immune microenvironment that promotes the osteogenic differentiation of BMSCs. In vivo experiments in a rabbit model demonstrated a significant improvement in the quantity and quality of the newly formed bone trabeculae within the scaffold under the contact osteogenesis pattern with a matched elastic modulus. These trabeculae exhibit robust connections to the external structure of the scaffold, accelerating the formation of an interlocking structure between the bone and implant and providing higher implantation stability. These findings suggest that the MAO-Ti2448 scaffold has significant potential as a bone defect repair material by regulating osteoimmunomodulation and osteogenesis to enhance osseointegration. This study demonstrates an optional strategy that combines the mechanism of reducing the elastic modulus with surface modification treatment, thereby extending the application scope of β-type titanium alloy.
生物材料支架,包括骨替代物,已经从主要作为生物惰性的结构元件发展为材料特性(如表面形貌和化学性质)通过影响干细胞和免疫微环境来主动指导骨再生的元件。Ti-6Al-4V(Ti6Al4V)植入物的弹性模量明显高于人体骨骼,可能导致应力屏蔽,因此需要提高钛合金植入物界面的稳定性。Ti-24Nb-4Zr-8Sn(Ti2448)是一种低弹性模量的β型钛合金,不含潜在有毒元素,本研究中使用了这种材料。我们采用 3D 打印技术制造了多孔支架结构,进一步降低植入物的结构刚度,使其接近松质骨的刚度。然后采用微弧氧化(MAO)表面改性技术在支架表面和内部形成微孔结构和亲水氧化陶瓷层。体外研究表明,MAO 处理可增强支架表面的增殖、黏附和成骨能力。MAO-Ti2448 氧化物层的化学成分被发现可增强骨髓间充质干细胞(BMSCs)中成骨基因的转录和表达,这可能与氧化物层中 NbO 和 SnO 的富集有关。MAO-Ti2448 支架具有协同的表面活性和低刚度,可显著激活抗炎型巨噬细胞表型,创造一种促进 BMSCs 成骨分化的免疫微环境。在兔模型的体内实验中,在与匹配弹性模量的接触成骨模式下,支架内新形成的骨小梁的数量和质量得到了显著改善。这些小梁与支架的外部结构有很强的连接,加速了骨与植入物之间的联锁结构的形成,提供了更高的植入物稳定性。这些发现表明,MAO-Ti2448 支架通过调节骨免疫调节和成骨作用来增强骨整合,具有作为骨缺损修复材料的巨大潜力。本研究展示了一种结合降低弹性模量与表面改性处理的可选策略,从而扩展了β型钛合金的应用范围。