Liu Wanjun, Heinrich Marcel A, Zhou Yixiao, Akpek Ali, Hu Ning, Liu Xiao, Guan Xiaofei, Zhong Zhe, Jin Xiangyu, Khademhosseini Ali, Zhang Yu Shrike
Biomaterials Innovation Research Center, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Adv Healthc Mater. 2017 Jun;6(12). doi: 10.1002/adhm.201601451. Epub 2017 May 2.
Bioprinting is an emerging technique for the fabrication of 3D cell-laden constructs. However, the progress for generating a 3D complex physiological microenvironment has been hampered by a lack of advanced cell-responsive bioinks that enable bioprinting with high structural fidelity, particularly in the case of extrusion-based bioprinting. Herein, this paper reports a novel strategy to directly bioprint cell-laden gelatin methacryloyl (GelMA) constructs using bioinks of GelMA physical gels (GPGs) achieved through a simple cooling process. Attributed to their shear-thinning and self-healing properties, the GPG bioinks can retain the shape and form integral structures after deposition, allowing for subsequent UV crosslinking for permanent stabilization. This paper shows the structural fidelity by bioprinting various 3D structures that are typically challenging to fabricate using conventional bioinks under extrusion modes. Moreover, the use of the GPG bioinks enables direct bioprinting of highly porous and soft constructs at relatively low concentrations (down to 3%) of GelMA. It is also demonstrated that the bioprinted constructs not only permit cell survival but also enhance cell proliferation as well as spreading at lower concentrations of the GPG bioinks. It is believed that such a strategy of bioprinting will provide many opportunities in convenient fabrication of 3D cell-laden constructs for applications in tissue engineering, regenerative medicine, and pharmaceutical screening.
生物打印是一种用于制造载有细胞的3D结构的新兴技术。然而,由于缺乏先进的细胞响应性生物墨水,生成3D复杂生理微环境的进展受到了阻碍,这种生物墨水能够实现具有高结构保真度的生物打印,特别是在基于挤出的生物打印情况下。在此,本文报道了一种新策略,即使用通过简单冷却过程获得的甲基丙烯酰化明胶(GelMA)物理凝胶(GPG)生物墨水直接生物打印载有细胞的GelMA结构。由于其剪切变稀和自愈特性,GPG生物墨水在沉积后可以保持形状并形成整体结构,从而允许随后进行紫外线交联以实现永久稳定。本文通过生物打印各种3D结构展示了结构保真度,这些结构在挤出模式下使用传统生物墨水通常很难制造。此外,使用GPG生物墨水能够在相对较低浓度(低至3%)的GelMA下直接生物打印高度多孔和柔软的结构。还证明了生物打印的结构不仅允许细胞存活,而且在较低浓度的GPG生物墨水下还能促进细胞增殖以及扩散。据信,这种生物打印策略将为方便制造用于组织工程、再生医学和药物筛选的载有细胞的3D结构提供许多机会。