The nerve center of organ engineering

Suradip Das (), Wisberty J. Gordián-Vélez, Jay R. Dave, Zarina S. Ali, Harry C. Ledebur and D. Kacy Cullen ()
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Suradip Das: University of Pennsylvania
Wisberty J. Gordián-Vélez: University of Pennsylvania
Jay R. Dave: University of Pennsylvania
Zarina S. Ali: University of Pennsylvania
Harry C. Ledebur: Southern Research
D. Kacy Cullen: University of Pennsylvania

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-64801-4

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