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@ARTICLE{Tiper:277741,
      author       = {Tiper, Yekaterina and Xie, Zhuoye and Hofemeier, Arne and
                      Lad, Heta and Luber, Mattias and Krawetz, Roman and Betz,
                      Timo and Zimmermann, Wolfram-Hubertus and Morton, Aaron B
                      and Segal, Steven S and Gilbert, Penney M},
      title        = {{O}ptimizing electrical field stimulation parameters
                      reveals the maximum contractile function of human skeletal
                      muscle microtissues.},
      journal      = {American journal of physiology / Cell physiology},
      volume       = {328},
      number       = {4},
      issn         = {0363-6143},
      address      = {Bethesda, Md.},
      publisher    = {American Physiological Society},
      reportid     = {DZNE-2025-00462},
      pages        = {C1160 - C1176},
      year         = {2025},
      abstract     = {Skeletal muscle microtissues are engineered to develop
                      therapies for restoring muscle function in patients.
                      However, optimal electrical field stimulation (EFS)
                      parameters to evaluate the function of muscle microtissues
                      remain unestablished. This study reports a protocol to
                      optimize EFS parameters for eliciting contractile force of
                      muscle microtissues cultured in micropost platforms. Muscle
                      microtissues were produced across an opposing pair of
                      microposts in polydimethylsiloxane and polymethyl
                      methacrylate culture platforms using primary, immortalized,
                      and induced pluripotent stem cell-derived myoblasts. In
                      response to EFS between needle electrodes, contraction
                      deflects microposts proportional to developed force. At 5 V,
                      pulse durations used for native muscle (0.1-1 ms) failed to
                      elicit contraction of microtissues; durations reported for
                      engineered muscle (5-10 ms) failed to elicit peak force.
                      Instead, pulse durations of 20-80 ms were required to elicit
                      peak twitch force across microtissues derived from five
                      myoblast lines. Similarly, although peak tetanic force
                      occurs at 20-50 Hz for native human muscles, it varied
                      across microtissues depending on the cell line type, ranging
                      from 7 to 60 Hz. A new parameter, the dynamic oscillation of
                      force, captured trends during rhythmic contractions, whereas
                      quantifying the duration-at-peak force provides an extended
                      kinetics parameter. Our findings indicate that muscle
                      microtissues have cell line type-specific contractile
                      properties, yet all contract and relax more slowly than
                      native muscle, implicating underdeveloped
                      excitation-contraction coupling. Failure to optimize EFS
                      parameters can mask the functional potential of muscle
                      microtissues by underestimating force production. Optimizing
                      and reporting EFS parameters and metrics is necessary to
                      leverage muscle microtissues for advancing skeletal muscle
                      therapies.NEW $\&$ NOTEWORTHY Electrical field stimulation
                      (EFS) parameters remain to be standardized for engineered
                      skeletal muscle. Herein, we report a protocol for defining
                      EFS parameters that elicit the maximal contractile force of
                      muscle microtissues cultivated in micropost devices and
                      highlight the value of developing appropriate metrics. The
                      dynamic oscillation of force and duration-at-peak force are
                      introduced as novel metrics of contraction kinetics.},
      keywords     = {Humans / Muscle Contraction: physiology / Electric
                      Stimulation: methods / Muscle, Skeletal: physiology /
                      Myoblasts: physiology / Myoblasts: cytology / Tissue
                      Engineering: methods / Induced Pluripotent Stem Cells:
                      physiology / Induced Pluripotent Stem Cells: cytology /
                      Cells, Cultured / Cell Line / contractile function (Other) /
                      electrical field stimulation (Other) / engineered skeletal
                      muscle (Other) / induced pluripotent stem cells (Other) /
                      micropost platform (Other)},
      cin          = {AG Fischer},
      ddc          = {000},
      cid          = {I:(DE-2719)1410002},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40019026},
      doi          = {10.1152/ajpcell.00308.2024},
      url          = {https://pub.dzne.de/record/277741},
}