Unlocking healing codes: Nanocarriers and signalling pathways modulation for wound repair

Wound healing is an intricate and dynamic biological phenomenon encompassing a well-orchestrated sequence of haemostasis, inflammatory, proliferative, and remodelling phases. Disruption or dysregulation of critical cellular signalling pathways in chronic wounds compromises tissue regeneration, prolongs inflammatory responses, and increases the susceptibility towards infections. Advances in nanotechnology have enabled the development of multifunctional and stimuli-responsive nanocarrier systems capable of modulating specific intracellular signalling cascades to re-establish physiological healing mechanisms. These nanosystems, fabricated from biocompatible polymers, lipids, or inorganic matrices, facilitate localized and sustained delivery of therapeutic agents within the wound microenvironment, thereby enhancing cellular uptake, minimizing systemic toxicity, and ensuring controlled bioavailability. By regulating pivotal pathways such as PI3K/Akt, Wnt/β-catenin, MAPK/ERK, TGF-β, and NF-κB, nanocarriers promote fibroblast proliferation, angiogenesis, extracellular matrix synthesis, and immune homeostasis, all of which are essential for effective tissue restoration. Furthermore, the incorporation of wound microenvironment-responsive elements enables these nanocarriers to release their payload in response to pathological cues, such as altered pH, elevated ROS levels, or enzyme activity, thereby ensuring precision therapy. Despite remarkable progress, translational challenges including biosafety evaluation, large-scale production, and regulatory hurdles remain. Collectively, targeted nanocarrier platforms represent a transformative paradigm in wound management, offering pathway-specific modulation for accelerated and functionally superior tissue repair in both acute and chronic wounds.