biostudies-literatureZhang PNatural Science Foundation of Chongqing MunicipalityNational Natural Science Foundation of China284-304https://www.ebi.ac.uk/biostudies/studies/S-EPMC12661998biostudies-literatureUnknown57The bone unit (BU) is a multicellular functional unit composed of neuromodulatory networks, bone tissue, and functional blood vessels. As a functional extension of bone regeneration, the BU coordinates neural signal, regeneration of the circulatory network and remodeling of the bone matrix through the neural-bone metabolic coupling mechanism. Currently, effective strategies are lacking to remodel the homeostasis of the neural-bone metabolic coupling, which in turn leads to impaired BU regeneration. Here, we constructed a 3D-printed biomimetic hydrogel scaffold, GGMN-GSE, to synergistically couple nerve-bone metabolism and restore BU regeneration through electrophysiological microenvironment reconstruction and functional cell recruitment. The GGMN layer (Grooved GelMA@MXene@NGF) incorporateBioactive materials3D printed scaffolds regulated by neural-bone metabolic coupling promote bone unit regeneration.PMC1266199882472404W2411085CSTB2022NSCQ-MSX0104Yang HJiang KLi YCao XLei YZhang HCui WYan CLi LLai NZhang Pfalse3D printed scaffolds regulated by neural-bone metabolic coupling promote bone unit regeneration.The bone unit (BU) is a multicellular functional unit composed of neuromodulatory networks, bone tissue, and functional blood vessels. As a functional extension of bone regeneration, the BU coordinates neural signal, regeneration of the circulatory network and remodeling of the bone matrix through the neural-bone metabolic coupling mechanism. Currently, effective strategies are lacking to remodel the homeostasis of the neural-bone metabolic coupling, which in turn leads to impaired BU regeneration. Here, we constructed a 3D-printed biomimetic hydrogel scaffold, GGMN-GSE, to synergistically couple nerve-bone metabolism and restore BU regeneration through electrophysiological microenvironment reconstruction and functional cell recruitment. The GGMN layer (Grooved GelMA@MXene@NGF) incorporate2026-01-01T00:00:00Z2026 Mar2026-06-05T21:23:01.359Z2026-05-22T03:08:49.068ZS-EPMC126619984132320010.1016/j.bioactmat.2025.10.031