An endoplasmic reticulum stress-responsive nanocomposite hydrogel for diabetic wound healing through a fibroblast-immune cell dual regulation hub.

ABSTRACT: Diabetic wounds exhibit excessive endoplasmic reticulum stress (ERS), which can lead to fibroblast dysfunction, abnormal natural killer (NK) cell activation, and imbalanced macrophage polarization. ERS exerts a bidirectional regulatory effect on wound fibroblasts and immune cells; simply inhibiting ERS impedes wound tissue regeneration. Existing hydrogels cannot precisely regulate ERS and synergistically repair multicell functional defects. Monocyte Chemoattractant Protein-1 (MCP-1), synthesized by fibroblasts in diabetic wounds, is a key molecular regulator of ERS and fibroblast function and a hub for fibroblast-immune cell interactions. This study constructed histidine-chitosan-fibroblast growth factor receptor (FGFR) agonist peptide 1 (FAP1)-pGPU6/GFP/Neo MCP-1-shRNA plasmid (HCFD) nano

SUBMITTER: Gao S 

PROVIDER: S-EPMC12551225 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature