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The nerve center of organ engineering

Author

Listed:
  • Suradip Das

    (University of Pennsylvania
    Corporal Michael J. Crescenz Veterans Affairs Medical Center)

  • Wisberty J. Gordián-Vélez

    (University of Pennsylvania
    Corporal Michael J. Crescenz Veterans Affairs Medical Center
    University of Pennsylvania)

  • Jay R. Dave

    (University of Pennsylvania
    Corporal Michael J. Crescenz Veterans Affairs Medical Center)

  • Zarina S. Ali

    (University of Pennsylvania)

  • Harry C. Ledebur

    (Southern Research)

  • D. Kacy Cullen

    (University of Pennsylvania
    Corporal Michael J. Crescenz Veterans Affairs Medical Center
    University of Pennsylvania)

Abstract

Engineering replacement organs is the next frontier in therapeutic technologies. Yet, the integration of innervation—critical for organ development, function, and homeostasis—remains underexplored. This review highlights the role of neural inputs in regulating critical organs including pancreas, liver, salivary gland, and spleen. We examine organ-specific neuroanatomy and emerging strategies to incorporate neuronal-axonal networks in engineered organs, drawing from innovations in scaffold design, multi-cell culture techniques, neural engineering, and biofabrication. Finally, we discuss tools for evaluating innervation across in vitro, preclinical, and clinical settings, advocating for innervation as a core design element in next-generation artificial organs.

Suggested Citation

  • Suradip Das & Wisberty J. Gordián-Vélez & Jay R. Dave & Zarina S. Ali & Harry C. Ledebur & D. Kacy Cullen, 2025. "The nerve center of organ engineering," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64801-4
    DOI: 10.1038/s41467-025-64801-4
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    References listed on IDEAS

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    1. Miho Ogawa & Masamitsu Oshima & Aya Imamura & Yurie Sekine & Kentaro Ishida & Kentaro Yamashita & Kei Nakajima & Masatoshi Hirayama & Tetsuhiko Tachikawa & Takashi Tsuji, 2013. "Functional salivary gland regeneration by transplantation of a bioengineered organ germ," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    2. Sergei Grebenyuk & Abdel Rahman Abdel Fattah & Manoj Kumar & Burak Toprakhisar & Gregorius Rustandi & Anja Vananroye & Idris Salmon & Catherine Verfaillie & Mark Grillo & Adrian Ranga, 2023. "Large-scale perfused tissues via synthetic 3D soft microfluidics," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
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