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Directing Neutrophil Fate via Sensory-Immune Interactions Accelerates Diabetic Bone Healing.

Created on 26 Jun 2026

Authors

Xuanyu Qi, Yijia Huang, Yuran Li, Jun Chen, Mingliang Zhou, Li Mei, Zeqian Xu, Sihan Lin, Xinquan Jiang

Published in

Research (Washington, D.C.). Volume 9. Pages 1320. Epub Jun 24, 2026.

Abstract

The intractability of diabetic bone defects mainly results from derailed inflammation. While peripheral neuropathy is a common comorbidity, whether sensory dysfunction contributes to uncontrolled inflammation in diabetes is poorly understood. Here, within diabetic bone defects, we show that diminished sensory innervation is coupled with disrupted immune dynamics, characterized by both delayed neutrophil chemotaxis and abnormal neutrophil retention that resulted from impaired macrophage efferocytosis. Therefore, we design a chocolate chip cookie-like scaffold, in which the surface-embedded microspheres function as "chips" enabling burst interleukin-8 (IL-8) release, while the surrounding matrix provides sustained nerve growth factor release from silk fibroin matrix. Timely neutrophil chemotaxis induced by IL-8 triggers bone healing via stem cell recruitment, which is reinforced by sensory innervation by inducing neutrophil N2 polarization. Notably, macrophages preferentially established intimate physical proximity to outgrowing neurites to form a synapse-like structure, where they restore efferocytosis driven by neuronal Galectin-3. Moreover, spatiotemporally regulating neuroimmune circuit enhances mandibular bone regeneration in diabetic rats, highlighting the therapeutic potential of neuroimmune interaction in programming diabetic inflammation resolution.

PMID:
42359047
Bibliographic data and abstract were imported from PubMed on 26 Jun 2026.

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