Inflammasome-derived biomarkers in wound healing: linking tissue repair, chronic inflammation, fibrosis, and precision therapeutics.

Wound healing is a highly organised biological event that involves hemostasis, inflammation, proliferation, and tissue remodelling processes. Dysregulated wound healing leads to the development of chronic wounds, characterised by persistent inflammation, impaired tissue regeneration, and extensive fibrosis. Recently, inflammasomes, which act as key regulators of innate immunity, have attracted increasing attention due to their important roles in wound healing. Indeed, inflammasome complexes, including NLRP3, AIM2, NLRC4, NLRP1, and Pyrin, activate inflammatory caspases, particularly caspase-1, which cleaves pro-IL-1β and pro-IL-18 into their mature, biologically active forms and promotes gasdermin D-dependent pyroptosis. Although transient inflammasome activation contributes to protective early inflammatory responses, including pathogen clearance and tissue repair, sustained or dysregulated activation promotes inflammatory caspase activation and pyroptosis, resulting in persistent inflammation, tissue injury, and aberrant extracellular matrix remodelling that can ultimately contribute to fibrosis and chronic wound development. This review focuses on state-of-the-art studies on the roles of inflammasome-derived biomarkers in wound healing. We highlight inflammasome-associated molecules as potential biomarkers of wound inflammation and tissue injury, while distinguishing their roles as mechanistic mediators from their potential as therapeutic targets. These include sensors, adaptors, inflammatory caspases, pyroptosis-related mediators, cytokines, and oxidative stress-associated factors. Our review highlights transcriptomic, proteomic, and metabolomic approaches for identifying candidate molecular biomarkers, while single-cell RNA sequencing and spatial transcriptomics provide cell-specific and spatial information that can improve biomarker validation and clinical stratification of wound states. Additionally, we discuss shared inflammasome-mediated mechanisms across diabetic foot ulcers, pressure ulcers, venous leg ulcers, burn wounds, and fibrotic scars, while highlighting condition-specific triggers, including metabolic dysfunction in diabetes, ischemia-reperfusion in pressure ulcers, venous hypertension, thermal injury, and dysregulated tissue remodelling in fibrosis.