Signalling pathways underlying the therapeutic potential of chitosan-based nanoformulations in wound healing: A...

Wound healing is a complex and dynamic biological process involving multiple overlapping phases of hemostasis, inflammation, proliferation, and remodeling, which are tightly regulated by various cellular and molecular signalling pathways. However, impaired healing due to infection, oxidative stress, and chronic conditions - such as diabetes - remains a significant clinical challenge. Chitosan, a naturally derived biopolymer, has attracted attention for its biocompatibility, biodegradability, antimicrobial activity, and ability to modulate biological responses. Recent advances in nanotechnology have enabled the development of chitosan-based nanoformulations, including nanoparticles, nanofibers, microneedles, nanogels, and nanocomposite scaffolds. These systems overcome the limitations of native chitosan and conventional wound dressings by providing enhanced drug delivery, stability, and controlled release. Importantly, these nanoformulations interact actively with critical signalling pathways, including transforming growth factor-beta (TGF-β)/Smad, phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), nuclear factor kappa B (NF-κB), and vascular endothelial growth factor (VEGF), promoting fibroblast proliferation, angiogenesis, collagen deposition, and inflammation resolution. This review highlights the mechanistic role and therapeutic potential of chitosan-based nanoformulations in accelerating wound healing, underscoring their promise as advanced, multifunctional platforms for effective acute and chronic wound management. © 2026 Society of Chemical Industry.