Department of Prosthodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, 639 Zhizaoju Road, Shanghai, 200011, China.
Adv Mater. 2017 Nov;29(43). doi: 10.1002/adma.201703795. Epub 2017 Oct 9.
The scaffold-free cell-sheet technique plays a significant role in stem-cell-based regeneration. Furthermore, growth factors are known to direct stem cell differentiation and enhance tissue regeneration. However, the absence of an effective means to incorporate growth factors into the cell sheets hinders further optimization of the regeneration efficiency. Here, a novel design of magnetically controlled "growth-factor-immobilized cell sheets" is reported. A new Fe O magnetic nanoparticle (MNP) coated with nanoscale graphene oxide (nGO@Fe O ) is developed to label stem cells and deliver growth factors. First, the nGO@Fe O MNPs can be easily swallowed by dental-pulp stem cells (DPSCs) and have no influence on cell viability. Thus, the MNP-labeled cells can be organized via magnetic force to form multilayered cell sheets in different patterns. Second, compared to traditional Fe O nanoparticles, the graphene oxide coating provides plenty of carboxyl groups to bind and deliver growth factors. Therefore, with these nGO@Fe O MNPs, bone-morphogenetic-protein-2 (BMP2) is successfully incorporated into the DPSCs sheets to induce more bone formation. Furthermore, an integrated osteochondral complex is also constructed using a combination of DPSCs/TGFβ3 and DPSCs/BMP2. All these results demonstrate that the new cell-sheet tissue-engineering approach exhibits promising potential for future use in regenerative medicine.
无支架细胞片技术在基于干细胞的再生中起着重要作用。此外，生长因子被认为可以指导干细胞分化并增强组织再生。然而，缺乏将生长因子有效纳入细胞片的方法，阻碍了再生效率的进一步优化。在这里，报道了一种新型的磁控“生长因子固定化细胞片”的设计。开发了一种新的 FeO 磁性纳米颗粒（MNP），其表面涂有纳米级氧化石墨烯（nGO@FeO），用于标记干细胞并传递生长因子。首先，nGO@FeO 纳米颗粒可以很容易地被牙髓干细胞（DPSCs）吞噬，并且对细胞活力没有影响。因此，通过磁力可以将标记有 MNP 的细胞组织成不同图案的多层细胞片。其次，与传统的 FeO 纳米颗粒相比，氧化石墨烯涂层提供了大量的羧基来结合和传递生长因子。因此，利用这些 nGO@FeO 纳米颗粒，成功地将骨形态发生蛋白 2（BMP2）纳入 DPSCs 片内，以诱导更多的骨形成。此外，还使用 DPSCs/TGFβ3 和 DPSCs/BMP2 的组合构建了一个整合的骨软骨复合体。所有这些结果表明，这种新的细胞片组织工程方法在再生医学中具有广阔的应用前景。
