Recent Advances: PDRN is known in the clinical field for its regenerative properties. This action is partially related to the stimulation of the purinergic system through adenosine A2A receptors (A2ARs). Recently, the topical anti-inflammatory effects of PDRN have aroused much interest, with a growing body of research supporting its use for the management of several inflammatory states. Critical Issues: Impaired tissue repair and several metabolic disorders are associated with chronic inflammation. Despite the growing clinical concern, an optimal and sustainable therapy for different inflammatory conditions has not yet been established, and current treatments are often limited by their short-term efficacies and side effects. Future Directions: The present review provides an updated summary of the ability of PDRN to control inflammation as observed in several in vitro studies, simplified models of the main biological mechanisms mediating its anti-inflammatory effect, and confirmed in vivo and clinical models. It analyzes the therapeutic potential of PDRN in terms of its mechanism of action through A2AR activation, its efficacy and its complications compared with those of current anti-inflammatory drugs.
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