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Hyeongjin Lee,1 WonJin Kim,1,2 JiUn Lee,1,2 Kyung Soon Park,1,3 James J. Yoo,1 Anthony Atala,1 Geun Hyung Kim,1,2,4,a) and Sang Jin Lee1,a)
1Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA
2Department of Biomechatronic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Suwon 16419, South Korea
3Department of Orthopedic Surgery, Chonnam National University Bitgoeul Hospital, Kwangju 61748, South Korea
4Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, South Korea
H.L. and W.K. contributed equally to this work.
a)Corresponding author
Abstract
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, in situ uniaxially aligned micro-topographical structure in the printed constructs is created by a fibrillation/leaching of poly(vinyl alcohol) after the printing process. The in vitro 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 in vivo, 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.
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