Biobased Elastomer Nanofibers Guide Light-Controlled Human-iPSC-Derived Skeletal Myofibers.
Biobased Elastomer Nanofibers Guide Light-Controlled Human-iPSC-Derived Skeletal Myofibers.
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DOI：
10.1002/adma.202110441
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发表时间：
2022-05
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生成模仿天然骨骼肌的细胞排列、成熟和功能的骨骼肌组织是疾病建模和再生治疗中持续存在的挑战。骨骼肌培养需要细胞外引导和机械支持来稳定收缩肌纤维。现有的基于微加工的解决方案受到复杂的制造步骤、低吞吐量以及测量动态收缩功能方面的挑战的限制。在这里，介绍了一种新型生物基纳米混合弹性体的合成和表征，该弹性体被电纺成对齐的纳米纤维片以模拟骨骼肌细胞外基质。该聚合物表现出与天然骨骼肌完美匹配的显着超弹性（约 11-50 kPa），极限应变约 1000%，弹性模量约 25 kPa。 单轴排列的纳米纤维引导成肌细胞排列，增强肌节形成，并促进肌管融合增加约 32%，肌纤维成熟增加约 50%。弹性体纳米纤维可稳定光遗传学控制的人类诱导多能干细胞衍生的骨骼肌纤维。当被蓝光激活时，与传统培养方法相比，肌纤维-纳米纤维混合结构保持显着更高（>200%）的收缩速度和比力（>280%）。工程肌纤维的功率密度约为 35 W m−3。该系统是一种有前景的新型骨骼肌组织模型，可应用于肌肉疾病建模、药物发现和肌肉再生。由新型生物基纳米混合聚合物制成的弹性纳米纤维片支持人类诱导多能干细胞衍生的骨骼肌纤维的分化和收缩功能。纳米纤维的受控排列提供了类似细胞外基质的指导，促进肌纤维分化和成熟。弹性体纳米纤维的超弹性特性可稳定光遗传学激活收缩并促进培养寿命。
Generating skeletal muscle tissue that mimics the cellular alignment, maturation, and function of native skeletal muscle is an ongoing challenge in disease modeling and regenerative therapies. Skeletal muscle cultures require extracellular guidance and mechanical support to stabilize contractile myofibers. Existing microfabrication‐based solutions are limited by complex fabrication steps, low throughput, and challenges in measuring dynamic contractile function. Here, the synthesis and characterization of a new biobased nanohybrid elastomer, which is electrospun into aligned nanofiber sheets to mimic the skeletal muscle extracellular matrix, is presented. The polymer exhibits remarkable hyperelasticity well‐matched to that of native skeletal muscle (≈11–50 kPa), with ultimate strain ≈1000%, and elastic modulus ≈25 kPa. Uniaxially aligned nanofibers guide myoblast alignment, enhance sarcomere formation, and promote a ≈32% increase in myotube fusion and ≈50% increase in myofiber maturation. The elastomer nanofibers stabilize optogenetically controlled human induced pluripotent stem cell derived skeletal myofibers. When activated by blue light, the myofiber–nanofiber hybrid constructs maintain a significantly higher (>200%) contraction velocity and specific force (>280%) compared to conventional culture methods. The engineered myofibers exhibit a power density of ≈35 W m−3. This system is a promising new skeletal muscle tissue model for applications in muscular disease modeling, drug discovery, and muscle regeneration. Elastomeric nanofiber sheets, made from a new biobased nanohybrid polymer, support the differentiation and contractile function of human induced pluripotent stem cell derived skeletal muscle fibers. The controlled alignment of nanofibers provides extracellular‐matrix‐like guidance, promoting myofiber differentiation and maturation. The hyperelastic properties of the elastomer nanofibers stabilize optogenetically activate contractions and promote culture longevity.