Li Jinhua, Wen Jin, Li Bin, Li Wan, Qiao Wei, Shen Jie, Jin Weihong, Jiang Xinquan, Yeung Kelvin W K, Chu Paul K
Department of Orthopaedics and Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong Pokfulam Hong Kong 999077 China.
Department of PhysicsDepartment of Materials Science and Engineering City University of Hong Kong Tat Chee Avenue Kowloon Hong Kong 999077 China.
Adv Sci (Weinh). 2017 Dec 18;5(2):1700678. doi: 10.1002/advs.201700678. eCollection 2018 Feb.
Understanding cell-biomaterial interactions is critical for the control of cell fate for tissue engineering and regenerative medicine. Here, cerium oxide nanoparticles (CeONPs) are applied at different Ce/Ce ratios (i.e., 0.46, 1.23, and 3.23) to titanium substrate surfaces by magnetron sputtering and vacuum annealing. Evaluation of the cytotoxicity of the modified surface to cultured rat bone marrow mesenchymal stem cells (BMSCs) reveals that the cytocompatibility and cell proliferation are proportional to the increases in Ce/Ce ratio on titanium surface. The bone formation capability induced by these surface modified titanium alloys is evaluated by implanting various CeONP samples into the intramedullary cavity of rat femur for 8 weeks. New bone formation adjacent to the implant shows a close relationship to the surface Ce/Ce ratio; higher Ce/Ce ratio achieves better osseointegration. The mechanism of this in vivo outcome is explored by culturing rat BMSCs and RAW264.7 murine macrophages on CeONP samples for different durations. The improvement in osteogenic differentiation capability of BMSCs is directly proportional to the increased Ce/Ce ratio on the titanium surface. Increases in the Ce/Ce ratio also elevate the polarization of the M2 phenotype of RAW264.7 murine macrophages, particularly with respect to the healing-associated M2 percentage and anti-inflammatory cytokine secretion. The manipulation of valence states of CeONPs appears to provide an effective modulation of the osteogenic capability of stem cells and the M2 polarization of macrophages, resulting in favorable outcomes of new bone formation and osseointegration.
了解细胞与生物材料的相互作用对于组织工程和再生医学中细胞命运的控制至关重要。在此，通过磁控溅射和真空退火将氧化铈纳米颗粒（CeONPs）以不同的Ce/Ce比（即0.46、1.23和3.23）应用于钛基体表面。对修饰表面对培养的大鼠骨髓间充质干细胞（BMSCs）的细胞毒性评估表明，细胞相容性和细胞增殖与钛表面Ce/Ce比的增加成正比。通过将各种CeONP样品植入大鼠股骨骨髓腔8周来评估这些表面改性钛合金诱导的骨形成能力。植入物附近的新骨形成与表面Ce/Ce比密切相关；较高的Ce/Ce比可实现更好的骨整合。通过在CeONP样品上培养大鼠BMSCs和RAW264.7小鼠巨噬细胞不同时间来探索这种体内结果的机制。BMSCs成骨分化能力的提高与钛表面Ce/Ce比的增加成正比。Ce/Ce比的增加还提高了RAW264.7小鼠巨噬细胞M2表型的极化，特别是在愈合相关的M2百分比和抗炎细胞因子分泌方面。CeONPs价态的调控似乎为干细胞的成骨能力和巨噬细胞的M2极化提供了有效的调节，从而导致新骨形成和骨整合的良好结果。
