Ying Guoliang, Jiang Nan, Parra Carolina, Tang Guosheng, Zhang Jingyi, Wang Hongjun, Chen Shixuan, Huang Ning-Ping, Xie Jingwei, Zhang Yu Shrike
Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Adv Funct Mater. 2020 Nov 11;30(46). doi: 10.1002/adfm.202003740. Epub 2020 Sep 6.
Direct injection of cell-laden hydrogels shows high potentials in tissue regeneration for translational therapy. The traditional cell-laden hydrogels are often used as bulk space fillers to tissue defects after injection, likely limiting their structural controllability. On the other hand, patterned cell-laden hydrogel constructs often necessitate invasive surgical procedures. To overcome these problems, herein, we report a unique strategy for encapsulating living human cells in a pore-forming gelatin methacryloyl (GelMA)-based bioink to ultimately produce injectable hierarchically macro-micro-nanoporous cell-laden GelMA hydrogel constructs through three-dimensional (3D) extrusion bioprinting. The hydrogel constructs can be fabricated into various shapes and sizes that are defect-specific. Due to the hierarchically macro-micro-nanoporous structures, the cell-laden hydrogel constructs can readily recover to their original shapes, and sustain high cell viability, proliferation, spreading, and differentiation after compression and injection. Besides, studies further reveal that the hydrogel constructs can integrate well with the surrounding host tissues. These findings suggest that our unique 3D-bioprinted pore-forming GelMA hydrogel constructs are promising candidates for applications in minimally invasive tissue regeneration and cell therapy.
直接注射载细胞水凝胶在组织再生的转化治疗中显示出巨大潜力。传统的载细胞水凝胶在注射后常被用作组织缺损的大量空间填充材料,这可能限制了它们的结构可控性。另一方面,图案化的载细胞水凝胶构建体通常需要侵入性手术操作。为了克服这些问题,在此,我们报告了一种独特的策略,即将活的人类细胞封装在基于明胶甲基丙烯酰(GelMA)的成孔生物墨水中,最终通过三维(3D)挤出生物打印生产出可注射的具有分级宏观-微观-纳米多孔结构的载细胞GelMA水凝胶构建体。水凝胶构建体可以制造成各种针对特定缺损的形状和尺寸。由于具有分级宏观-微观-纳米多孔结构,载细胞水凝胶构建体能够很容易地恢复到其原始形状,并且在压缩和注射后能维持高细胞活力、增殖、铺展和分化。此外,研究进一步表明,水凝胶构建体能够与周围的宿主组织良好整合。这些发现表明,我们独特的3D生物打印成孔GelMA水凝胶构建体有望应用于微创组织再生和细胞治疗。