Three-dimensional tissue-engineered skeletal muscle for laryngeal reconstruction.

Three-dimensional tissue-engineered skeletal muscle for laryngeal reconstruction.
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DOI:
10.1002/lary.26771
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发表时间:
2018-03
期刊:
The Laryngoscope
影响因子:
--
通讯作者:
Halum S
Halum S
中科院分区:
其他
文献类型:
--
作者:
Brookes S;Voytik-Harbin S;Zhang H;Halum S

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用于喉部重建的组织工程三维(3D)肌肉结构的需求尚未得到满足。功能性工程肌肉可用于修复肿瘤后或创伤性缺陷,或在轻瘫/瘫痪的情况下将声带置于内侧。目前还不存在具有足够体积、融入宿主组织并恢复功能的自体、有组织、工程化的肌肉。从 F344 大鼠中分离出原代骨骼肌祖细胞 (MPC)。 3D 肌肉结构是通过将 MPC 封装在定制的胶原蛋白配方中并在被动张力下培养而创建的。肌肉特异性免疫组织化学和共聚焦显微镜用于评估肌肉组织分化。培养两周后,将肌肉结构植入大鼠喉部手术造成的缺损处。在1个月和3个月时进行死后功能测试和组织学检查。共聚焦显微镜的免疫组织化学证明了分化良好的肌管,这些肌管在体外排列良好并分布在整个工程构建体中。有证据表明,术后 1 个月喉部功能恢复正常,表现为安全吞咽(无误吸事件)、体重增加和动物存活率良好。尸检标本在离体测试中证明了功能性肌肉收缩,组织学证实了其与宿主组织的整合。这是第一项证明功能性 3D 组织工程骨骼肌可以由原代 MPC 和标准化寡聚胶原蛋白开发的研究。总的来说,这些发现可能对自体喉肌修复和重建具有巨大的临床意义。不适用
There is an unmet need for tissue-engineered three-dimensional (3D) muscle constructs for laryngeal reconstruction. Functional engineered muscle could be used to repair post-oncologic or traumatic defects, or to medialize the vocal fold in cases of paresis/paralysis. Autologous, organized, engineered muscle that has adequate bulk, integrates into host tissue, and restores function does not currently exist. Primary skeletal muscle progenitor cells (MPCs) were isolated from F344 rats. 3D muscle constructs were created by encapsulating MPCs via flow-alignment in a customized collagen formulation and cultured under passive tension. Muscle-specific immunohistochemistry and confocal microscopy were used to evaluate muscle tissue differentiation. After 2 weeks of culture, muscle constructs were implanted into surgically created defects in the rat larynx. Post mortem function testing and histology was performed at 1 and 3 months. Immunohistochemistry with confocal microscopy demonstrated well differentiated myotubes which were well aligned and distributed throughout the engineered construct in vitro. There was evidence of restoration of normal laryngeal function at 1 month post-op, as indicated by safe swallow (no aspiration events), weight gain, and excellent animal survival. Post-mortem specimens demonstrated functional muscle contraction on ex vivo testing, and histology confirmed integration into host tissue. This is the first study to demonstrate that functional, 3D tissue-engineered skeletal muscle can be developed from primary MPCs and standardized oligomeric collagen. Collectively, these findings may have tremendous clinical implications for autologous laryngeal muscle repair and reconstruction. NA
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