Smart Biomaterials Group, Nano-Life Field, Biomaterials Unit, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
Physical Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
Biomaterials. 2014 May;35(15):4441-53. doi: 10.1016/j.biomaterials.2014.01.074. Epub 2014 Mar 5.
Understanding and controlling cell proliferation on biomaterial surfaces is critical for scaffold/artificial-niche design in tissue engineering. The mechanism by which underlying integrin ligates with functionalized biomaterials to induce cell proliferation is still not completely understood. In this study, poly-l-lactide (PL) scaffold surfaces were functionalized using layers of cerium oxide nanoparticles (CNPs), which have recently attracted attention for use in therapeutic application due to their catalytic ability of Ce(4+) and Ce(3+) sites. To isolate the influence of Ce valance states of CNPs on cell proliferation, human mesenchymal stem cells (hMSCs) and osteoblast-like cells (MG63) were cultured on the PL/CNP surfaces with dominant Ce(4+) and Ce(3+) regions. Despite cell type (hMSCs and MG63 cells), different surface features of Ce(4+) and Ce(3+) regions clearly promoted and inhibited cell spreading, migration and adhesion behavior, resulting in rapid and slow cell proliferation, respectively. Cell proliferation results of various modified CNPs with different surface charge and hydrophobicity/hydrophilicity, indicate that Ce valence states closely correlated with the specific cell morphologies and cell-material interactions that trigger cell proliferation. This finding suggests that the cell-material interactions, which influence cell proliferation, may be controlled by introduction of metal elements with different valence states onto the biomaterial surface.
理解并控制生物材料表面的细胞增殖对于组织工程中的支架/人工龛设计至关重要。细胞外基质整合素与功能化生物材料结合以诱导细胞增殖的机制尚不完全清楚。在这项研究中，使用氧化铈纳米粒子（CNPs）的层对聚-l-乳酸（PL）支架表面进行功能化，由于 Ce(4+)和 Ce(3+)位点的催化能力，CNPs 最近引起了治疗应用的关注。为了分离 CNPs 的 Ce 价态对细胞增殖的影响，将人骨髓间充质干细胞（hMSCs）和成骨样细胞（MG63）培养在具有主导 Ce(4+)和 Ce(3+)区域的 PL/CNP 表面上。尽管细胞类型（hMSCs 和 MG63 细胞）不同，但 Ce(4+)和 Ce(3+)区域的不同表面特征明显促进和抑制了细胞铺展、迁移和粘附行为，从而分别导致快速和缓慢的细胞增殖。具有不同表面电荷和疏水性/亲水性的各种改性 CNPs 的细胞增殖结果表明，Ce 价态与引发细胞增殖的特定细胞形态和细胞-材料相互作用密切相关。这一发现表明，通过在生物材料表面引入具有不同价态的金属元素，可以控制影响细胞增殖的细胞-材料相互作用。
