Lee Hyeongjin, Kim WonJin, Lee JiUn, Park Kyung Soon, Yoo James J, Atala Anthony, Kim Geun Hyung, Lee Sang Jin
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
Appl Phys Rev. 2021 Jun;8(2):021405. doi: 10.1063/5.0039639.
To achieve rapid skeletal muscle function restoration, many attempts have been made to bioengineer functional muscle constructs by employing physical, biochemical, or biological cues. Here, we develop a self-aligned skeletal muscle construct by printing a photo-crosslinkable skeletal muscle extracellular matrix-derived bioink together with poly(vinyl alcohol) that contains human muscle progenitor cells. To induce the self-alignment of human muscle progenitor cells, uniaxially aligned micro-topographical structure in the printed constructs is created by a fibrillation/leaching of poly(vinyl alcohol) after the printing process. The results demonstrate that the synergistic effect of tissue-specific biochemical signals (obtained from the skeletal muscle extracellular matrix-derived bioink) and topographical cues [obtained from the poly(vinyl alcohol) fibrillation] improves the myogenic differentiation of the printed human muscle progenitor cells with cellular alignment. Moreover, this self-aligned muscle construct shows the accelerated integration with neural networks and vascular ingrowth , resulting in rapid restoration of muscle function. We demonstrate that combined biochemical and topographic cues on the 3D bioprinted skeletal muscle constructs can effectively reconstruct the extensive muscle defect injuries.
为实现快速的骨骼肌功能恢复，人们已进行了诸多尝试，通过利用物理、生化或生物学线索来生物工程构建功能性肌肉组织。在此，我们通过打印一种可光交联的源自骨骼肌细胞外基质的生物墨水以及含有人类肌肉祖细胞的聚乙烯醇，开发出一种自我排列的骨骼肌组织。为诱导人类肌肉祖细胞的自我排列，在打印过程后通过聚乙烯醇的原纤化/浸出，在打印构建物中创建单轴排列的微地形结构。结果表明，组织特异性生化信号（源自骨骼肌细胞外基质衍生的生物墨水）和地形线索（源自聚乙烯醇原纤化）的协同作用，通过细胞排列改善了打印的人类肌肉祖细胞的成肌分化。此外，这种自我排列的肌肉组织显示出与神经网络和血管向内生长的加速整合，从而实现肌肉功能的快速恢复。我们证明，3D生物打印骨骼肌构建物上的生化和地形线索相结合，能够有效地重建广泛的肌肉缺损损伤。
