Nanotherapeutics for Wound healing: A review of Mechanotransduction, Cellular Senescence, and Regenerative signaling mechanisms and therapeutics development

SWound healing is a dynamic process regulated by mechanical cues, inflammation, cellular senescence, extracellular matrix remodeling, and regenerative signaling. Dysregulated mechanotransduction can alter cell behavior, gene expression, and tissue architecture, contributing to persistent inflammation, senescence, infection, and chronic non-healing wounds. Recent advances in nanotherapeutics offer opportunities to target these interconnected mechanisms with improved spatial and temporal precision. Nanocarriers, including liposomes, polymeric nanoparticles, and multifunctional nanostructures, enable targeted and stimulus-responsive delivery of therapeutic agents while protecting them from the hostile wound microenvironment. Functional nanoparticles and nanozymes can provide antimicrobial, antibiofilm, and antioxidant effects, thereby restoring a favorable environment for tissue repair. Emerging nanotherapeutic strategies also target cellular senescence and inflammatory pathways while minimizing effects on healthy cells. Biomimetic nanomaterials and extracellular matrix-mimicking scaffolds can provide mechanical and biochemical cues that enhance cell adhesion, migration, proliferation, and regeneration. Multifunctional platforms further modulate growth-factor signaling, transcriptional activity, and calcium-dependent pathways associated with tissue rejuvenation. Immunomodulatory nanotherapies can promote macrophage polarization toward pro-reparative phenotypes and regulate neutrophil responses, while smart systems capable of sensing pathological biomarkers may enable adaptive wound treatment. Collectively, these approaches support integrated control of the mechanical, inflammatory, and regenerative components of wound healing. However, rigorous preclinical and clinical evaluation across diverse wound types remains essential for establishing their safety, efficacy, and translational potential.