Deciphering skin architecture, wound pathophysiology and molecular mechanisms of healing: insights into immune response and therapeutic strategies

Abstract

Skin not only serves as a protective barrier, but also as a dynamic immunological and sensory organ responsible for complex physiological processes. Disruption through trauma, surgery, burns or chronic metabolic disease initiates a tightly regulated healing cascade involving inflammatory signaling, extracellular matrix remodeling, angiogenesis and coordinated cellular responses. While acute wounds generally progress through orderly phases of repair, chronic wounds such as diabetic foot ulcers, venous ulcers and pressure injuries become arrested in persistent inflammatory states characterized by protease imbalance, senescent cell accumulation, impaired vascularization and colonization of microbial biofilms, contributing to significant global morbidity and healthcare burden. This review integrates structural biology, immune mechanisms and molecular signaling pathways that govern wound repair, clearly delineating the differences between acute and chronic healing. Particular emphasis is placed on inflammation-driven dysregulation, extracellular matrix dynamics and defective angiogenesis that underpin chronic wound pathology. Rare and often underrepresented wound types, including radiation-induced and autoimmune-associated lesions, are also discussed to provide a broader and clinically relevant perspective. Importantly, the review highlights translational and technological advances transforming wound management, including self-healing hydrogels, nanofiber scaffolds, bioactive and stimuli-responsive dressings, biosensor-integrated platforms, cellular and molecular therapies and AI-assisted diagnostic systems. These innovations exemplify a shift from passive wound coverage toward biointeractive, precision-guided and microenvironment-responsive therapeutic strategies. By bridging immunopathology, regenerative medicine, nanobiotechnology and digital health platforms within a single cohesive narrative, this review serves as a comprehensive and integrative resource for academicians, clinicians, translational researchers and pharmaceutical innovators seeking a mechanistically grounded yet application-oriented understanding of modern wound care.