biostudies-literatureUnknownPollard KJNCATS NIH HHSNINDS NIH HHSMicrophysiological systems (MPSs) are engineered, in vitro platforms which have been established as viable alternatives to animal models for pre-clinical research with unique advantages over conventional model systems. Many MPSs utilize 3-dimensional (3D) tissue constructs that enable biomimetic cell-cell interactions, allow for extended culture periods, and provide the time necessary for the emergence of physical and physiological characteristics of more mature tissues. Here, we present a novel MPS using human induced pluripotent stem cell (hiPSC)-derived spinal cord dorsal horn (SCDH) spheroids co-cultured with hiPSC-derived dorsal root ganglion (DRG) sensory spheroids in a microengineered hydrogel system to create a "connectoid" model of afferent pain circuitry. SCDH spheroids were funcbioRxiv : the preprint server for biology2025.08.31.673344https://www.ebi.ac.uk/biostudies/studies/S-EPMC12424732biostudies-literatureHuman microphysiological model of dorsal root ganglion-spinal cord dorsal horn circuitry recapitulates opioid induced effects.PMC12424732UH3 TR003150F32 NS106740Moore MJPollard KJIyer NRAshton RSBosak ASeipel FRfalseHuman microphysiological model of dorsal root ganglion-spinal cord dorsal horn circuitry recapitulates opioid induced effects.Microphysiological systems (MPSs) are engineered, in vitro platforms which have been established as viable alternatives to animal models for pre-clinical research with unique advantages over conventional model systems. Many MPSs utilize 3-dimensional (3D) tissue constructs that enable biomimetic cell-cell interactions, allow for extended culture periods, and provide the time necessary for the emergence of physical and physiological characteristics of more mature tissues. Here, we present a novel MPS using human induced pluripotent stem cell (hiPSC)-derived spinal cord dorsal horn (SCDH) spheroids co-cultured with hiPSC-derived dorsal root ganglion (DRG) sensory spheroids in a microengineered hydrogel system to create a "connectoid" model of afferent pain circuitry. SCDH spheroids were func2025-01-01T00:00:00Z2025 Sep2026-04-27T03:13:47.658Z2026-04-27T03:09:29.864ZS-EPMC124247324095011310.1101/2025.08.31.673344