The nerve center of organ engineering.

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.