Physiological and pathological roles of inflammasomes in wound healing

Wound healing is a dynamic, tightly regulated process involving hemostasis, inflammation, proliferation, and remodeling. Effective progression through these phases requires coordinated activation and resolution of innate immune responses. Inflammasomes—multiprotein platforms that sense cellular stress and microbial products—have emerged as crucial regulators of sterile inflammation during tissue repair. Canonical inflammasomes such as NLRP3, NLRC4, and AIM2 promote maturation of interleukin-1β and interleukin-18, and trigger pyroptotic cell death, orchestrating the inflammatory milieu required for early healing. However, dysregulated or persistent inflammasome activation contributes to pathological inflammation, tissue damage, and impaired healing, especially in diabetic wounds and chronic ulcers. Hyperglycemia-driven oxidative stress, impaired autophagy, and aberrant macrophage polarization amplify inflammasome activity, perpetuating non-resolving inflammation. In parallel, chronic wound pathogens like Pseudomonas aeruginosa can subvert inflammasome responses—via effectors such as ExoT that inhibit Crk/Abl signaling and dampen NLRC4 activation—promoting persistent infection. This review integrates current evidence on the physiological and pathological roles of inflammasomes in wound healing, highlighting mechanisms of their dysregulation in diabetic and chronic wounds. We also discuss emerging therapeutic strategies, including selective inflammasome inhibitors, antioxidants, autophagy inducers, and novel biomaterials that locally modulate inflammasome activity. Understanding the dual role of inflammasomes and their context-dependent regulation could enable targeted interventions to restore balanced inflammation and accelerate wound repair.