biostudies-literatureZhan CUniversity of Hong Kong Seed Fund for PI Research - Translational and Applied ResearchNational Natural Science Foundation of China Young Scientists Funde06438https://www.ebi.ac.uk/biostudies/studies/S-EPMC12561402biostudies-literatureUnknown12(40)Diabetes exacerbates the development and progression of periodontitis through the aggravation of persistent inflammation and tissue destruction. While the impact of diabetes on peripheral sensory nerves is well-documented, little is known about the role of diabetic neuropathy in bone destruction in diabetes-associated periodontitis. Herein, a significant loss of periodontal nerves is observed in the diabetic state of db/db mice, with trigeminal ganglion neurons showing decreased autophagy. These mice exhibit decreased density of calcitonin gene-related peptide (CGRP)⁺ nerves, correlating with the progression of diabetes and inflammatory state. Furthermore, diabetic mice with periodontitis show greater alveolar bone loss, which can be phenocopied by periodontal denervation. Importantly, CGRP receptor-related components are found to be expressed in periodontal endothelial cells. In both diabetic and denervated periodontium, the loss of CGRP signaling is associated with the reduction of type H vessel density and coupled osterix⁺ osteoprogenitors. To elaborate further, an injectable reactive oxygen species-responsive poly(vinyl alcohol) (PVA)/tsPBA hydrogel is developed for sustained CGRP delivery. Notably, the CGRP-loaded hydrogels promote alveolar bone regeneration via inducing type H vessel formation in diabetic mice. The findings highlight that diabetes-induced sensory nerve damage may exacerbate periodontitis-induced bone loss, and CGRP@PVA/tsPBA hydrogels offer a promising therapeutic strategy for bone regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany)CGRP-Loaded ROS-Responsive Hydrogel Restores Neuro-Angiogenic Signaling to Promote Bone Regeneration in Diabetes-Associated Periodontitis.PMC125614022403101930220310070582401109Tsoi JKHZhan CDai QRen JWang WLin YJin LYe ZfalseCGRP-Loaded ROS-Responsive Hydrogel Restores Neuro-Angiogenic Signaling to Promote Bone Regeneration in Diabetes-Associated Periodontitis.Diabetes exacerbates the development and progression of periodontitis through the aggravation of persistent inflammation and tissue destruction. While the impact of diabetes on peripheral sensory nerves is well-documented, little is known about the role of diabetic neuropathy in bone destruction in diabetes-associated periodontitis. Herein, a significant loss of periodontal nerves is observed in the diabetic state of db/db mice, with trigeminal ganglion neurons showing decreased autophagy. These mice exhibit decreased density of calcitonin gene-related peptide (CGRP)⁺ nerves, correlating with the progression of diabetes and inflammatory state. Furthermore, diabetic mice with periodontitis show greater alveolar bone loss, which can be phenocopied by periodontal denervation. Importantly, CGRP receptor-related components are found to be expressed in periodontal endothelial cells. In both diabetic and denervated periodontium, the loss of CGRP signaling is associated with the reduction of type H vessel density and coupled osterix⁺ osteoprogenitors. To elaborate further, an injectable reactive oxygen species-responsive poly(vinyl alcohol) (PVA)/tsPBA hydrogel is developed for sustained CGRP delivery. Notably, the CGRP-loaded hydrogels promote alveolar bone regeneration via inducing type H vessel formation in diabetic mice. The findings highlight that diabetes-induced sensory nerve damage may exacerbate periodontitis-induced bone loss, and CGRP@PVA/tsPBA hydrogels offer a promising therapeutic strategy for bone regeneration.2025-01-01T00:00:00Z2025 Oct2026-06-05T09:12:29.704Z2026-05-15T03:12:23.572ZS-EPMC125614024075531710.1002/advs.202506438