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3D 生物打印的人类骨骼肌构建体用于肌肉功能恢复。

3D Bioprinted Human Skeletal Muscle Constructs for Muscle Function Restoration.

机构信息

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, United States.

Department of Orthopedic Surgery, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-Do, 420-726, Republic of Korea.

出版信息

Sci Rep. 2018 Aug 17;8(1):12307. doi: 10.1038/s41598-018-29968-5.

Abstract

A bioengineered skeletal muscle tissue as an alternative for autologous tissue flaps, which mimics the structural and functional characteristics of the native tissue, is needed for reconstructive surgery. Rapid progress in the cell-based tissue engineering principle has enabled in vitro creation of cellularized muscle-like constructs; however, the current fabrication methods are still limited to build a three-dimensional (3D) muscle construct with a highly viable, organized cellular structure with the potential for a future human trial. Here, we applied 3D bioprinting strategy to fabricate an implantable, bioengineered skeletal muscle tissue composed of human primary muscle progenitor cells (hMPCs). The bioprinted skeletal muscle tissue showed a highly organized multi-layered muscle bundle made by viable, densely packed, and aligned myofiber-like structures. Our in vivo study presented that the bioprinted muscle constructs reached 82% of functional recovery in a rodent model of tibialis anterior (TA) muscle defect at 8 weeks of post-implantation. In addition, histological and immunohistological examinations indicated that the bioprinted muscle constructs were well integrated with host vascular and neural networks. We demonstrated the potential of the use of the 3D bioprinted skeletal muscle with a spatially organized structure that can reconstruct the extensive muscle defects.

摘要

需要一种生物工程化的骨骼肌组织作为自体组织皮瓣的替代品,它模拟天然组织的结构和功能特征,用于重建手术。基于细胞的组织工程原理的快速发展使得体外创建细胞化的类似肌肉的构建体成为可能;然而,目前的制造方法仍然局限于构建具有高度可行的、有组织的细胞结构的三维(3D)肌肉构建体,具有未来进行人体试验的潜力。在这里,我们应用 3D 生物打印策略来制造一种由人原代肌肉祖细胞(hMPC)组成的可植入的、生物工程化的骨骼肌组织。生物打印的骨骼肌组织显示出高度组织化的多层肌束,由有活力的、紧密堆积的、排列整齐的肌纤维样结构组成。我们的体内研究表明,在植入后 8 周的胫骨前肌(TA)肌肉缺损的啮齿动物模型中,生物打印的肌肉构建体达到了 82%的功能恢复。此外,组织学和免疫组织化学检查表明,生物打印的肌肉构建体与宿主血管和神经网络很好地整合在一起。我们证明了使用具有空间组织结构的 3D 生物打印骨骼肌的潜力,这种结构可以重建广泛的肌肉缺损。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdd5/6098064/2931c8bc9ff1/41598_2018_29968_Fig1_HTML.jpg

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