State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710054, P. R. China.
Department of Materials Science and Engineering Institute of Biomaterials, Friedrich-Alexander-University Erlangen-Nuremberg, 91058, Erlangen, Germany.
Small. 2022 Mar;18(12):e2104996. doi: 10.1002/smll.202104996. Epub 2022 Feb 1.
Bioprinting has seen significant progress in recent years for the fabrication of bionic tissues with high complexity. However, it remains challenging to develop cell-laden bioinks exhibiting superior physiochemical properties and bio-functionality. In this study, a multifunctional nanocomposite bioink is developed based on amine-functionalized copper (Cu)-doped mesoporous bioactive glass nanoparticles (ACuMBGNs) and a hydrogel formulation relying on dynamic covalent chemistry composed of alginate dialdehyde (oxidized alginate) and gelatin, with favorable rheological properties, improved shape fidelity, and structural stability for extrusion-based bioprinting. The reversible dynamic microenvironment in combination with the impact of cell-adhesive ligands introduced by aminated particles enables the rapid spreading (within 3 days) and high survival (>90%) of embedded human osteosarcoma cells and immortalized mouse bone marrow-derived stroma cells. Osteogenic differentiation of primary mouse bone marrow stromal stem cells (BMSCs) and angiogenesis are promoted in the bioprinted alginate dialdehyde-gelatin (ADA-GEL or AG)-ACuMBGN scaffolds without additional growth factors in vitro, which is likely due to ion stimulation from the incorporated nanoparticles and possibly due to cell mechanosensing in the dynamic matrix. In conclusion, it is envisioned that these nanocomposite bioinks can serve as promising platforms for bioprinting complex 3D matrix environments providing superior physiochemical and biological performance for bone tissue engineering.
近年来，生物打印技术在制造具有高复杂性的仿生组织方面取得了重大进展。然而，开发具有优异物理化学性能和生物功能的细胞负载生物墨水仍然具有挑战性。在这项研究中，开发了一种基于胺功能化铜（Cu）掺杂介孔生物活性玻璃纳米颗粒（ACuMBGNs）和水凝胶配方的多功能纳米复合生物墨水，该配方依赖于由藻酸盐二醛（氧化藻酸盐）和明胶组成的动态共价化学，具有良好的流变性能、提高的形状保真度和结构稳定性，适用于基于挤出的生物打印。可逆动态微环境与引入的细胞黏附配体的影响相结合，使嵌入的人骨肉瘤细胞和永生化小鼠骨髓基质细胞能够快速扩散（在 3 天内）和高存活率（>90%）。在体外，未添加额外生长因子的情况下，原代小鼠骨髓基质干细胞（BMSCs）的成骨分化和血管生成在生物打印的藻酸盐二醛-明胶（ADA-GEL 或 AG）-ACuMBGN 支架中得到促进，这可能归因于掺入的纳米颗粒的离子刺激，也可能归因于动态基质中的细胞机械感觉。总之，可以预见，这些纳米复合生物墨水可以作为生物打印复杂 3D 基质环境的有前途的平台，为骨组织工程提供优异的物理化学和生物学性能。
