Inflammation is an inevitable and potentially harmful response to tissue damage or trauma and understanding the molecular basis underlying the body’s systemic inflammatory response, within the context of the injury, offers significant therapeutic opportunity. For example, chronic cutaneous wounds remain stalled in the initial inflammatory phase of wound healing and are generally unresponsive to conventional treatments, as they do not address the underlying pathophysiology of the disease. Understanding the molecular cascade for normal, acute response to tissue damage provides context for what has become aberrant in chronic inflammation, such as chronic wounds. Our therapeutic approach effectively “reboots” the normal injury response mechanisms and serves to reduce and calm excessive inflammatory responses, accelerate re-epithelialization, promote normal healing and prevent long-term complications.