Pathogenetic approaches to enhancing local treatment strategies for skin burns

This study examined the pathogenetic mechanisms of burn wound deepening and confirmed approaches for optimizing local burn treatment strategies. In Russia, approximately 300,000 burn cases are registered annually, the majority of which are superficial and partial-thickness burns. A well-studied occurrence in burn pathology is the progressive deepening of wounds over time. Fundamental principles explaining this phenomenon were established long ago. Some tissues undergo instantaneous necrosis due to thermal exposure (primary necrosis zone), whereas other tissues undergo progressive necrosis caused by a cascade of complex pathogenetic changes (secondary necrosis zone). Understanding the early pathogenetic mechanisms initiated in the early phase of thermal injury may contribute to the development of new therapeutic approaches. A comprehensive literature review was conducted using electronic databases (i.e., eLibrary, PubMed, Scopus, Google Scholar, ResearchGate, and ScienceDirect) to analyze Russian and international studies on burn necrosis progression. The primary contributors to secondary necrosis in skin burns (i.e., tissue hyperthermia, microcirculatory dysfunction, and inflammation) are associated with inflammatory cascade reactions involving multiple mechanisms, including reactive oxygen species-mediated cell damage, apoptosis initiation, neutrophil extracellular trap formation, autophagy, and other processes. Burn-induced cell death leads to the release of damage-associated molecular patterns, whereas skin barrier disruption facilitates the penetration of pathogen-associated molecular patterns into tissues, amplifying the inflammatory response. These processes may be prevented, which may help reduce the depth of the burn. Experimental and clinical studies on various pharmacological agents and drug formulations aimed at stopping necrosis progression indicate that erythropoietin derivatives, anti-cytokine agents and their combinations, complement activation inhibitors, antioxidants, mitophagy stimulators (e.g., PTEN-induced kinase 1 and ubiquitin ligase), and other active compounds reduce necrotic expansion. Furthermore, nanoemulsions and hydrogels developed using microfluidic technology, along with other modern drug formulations, potentially prevent progressive tissue necrosis and enhance the biological availability of active substances. Therefore, multi-targeted therapies that address all pathogenetic components of necrosis progression should be developed.