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A non-healing wound is a common problem associated with diabetes mellitus. Chronic inflammation, challenging re-epithelization, unusual growth factors, and impaired angiogenesis are the multifactorial events that contribute to impaired wounds. Hence, in the present work, an innovative GA-CSNPs nanocomposite scaffold has been fabricated by integrating Gallic acid (GA) loaded chitosan nanoparticles (GA-CSNPs) into a genipin crosslinked collagen-fibrin (Col-fibrin) scaffold as wound dressing material. The in vitro RT-PCR study carried out using NIH/3T3 mouse fibroblast cells showed that treatment with GA-CSNPs nanocomposite scaffold aids in an upsurge in the expression of Col-I, III, and VEGF, which further supports the synthesis of extracellular matrix, increases neovascularization and development of the established vascular system. In vivo wound contraction study results revealed that diabetic wounds treated with GA-CSNPs nanocomposite scaffold show a faster rate of wound closure (p < .001), histopathology results showed accelerated fibroblast cell migration, reduction of the inflammatory cells, enhanced collagen along with hexosamine synthesis. In addition, immunohistochemistry results showed increased vascularization, a significant decrease in macrophage recruitment, and reduced expression of MMP-9 compared to the Col-fibrin scaffold and Control groups. Overall data suggest that the fabricated GA-CSNPs nanocomposite porous 3-D scaffold can be a hopeful therapeutic choice for diabetic wound management., (© 2022 Wiley Periodicals LLC.)