The management of chronic wounds is an enormous clinical and economic burden on the health care system. In addition to the economic impact, the reduced quality of life and mortality associated with chronic wounds are considerable.
Wound healing consists of consecutive and partially overlapping inflammatory, proliferation, and remodeling phases. For successful wound healing to occur, a delicate balance of this process needs to be maintained and regulated.
The inflammatory phase starts immediately after the wound occurs and is associated with migration of immune cells to the wounded area. At the site of injury, the immune cells aid in clearing infection and damaged cells. By secreting different signaling molecules, including cytokines, chemokines, and growth factors they recruit additional immune cells and change the function of the specialized immune cells called to macrophages to resolve the inflammation. If the inflammatory phase is not resolved, wounds cannot heal and become chronic. The resolution of the inflammation initiates the proliferation phase of wound healing by stimulating epithelial-to-mesenchymal transition (EMT), angiogenesis, and by activating fibroblasts to proliferate and release collagen. This process results in re-epithelization, angiogenesis and formation of granulation tissue. Closure of the wound is finally established by substantial tissue remodeling, including the breakdown and reestablishment of the basement membranes and the extracellular matrix (ECM).
Plasminogen has been shown to have an essential and active role in all three phases of wound healing. First, it accumulates in the wounded area during the first day of wound healing, in which it activates signal transduction and potentiates the early inflammatory response and leads to recruitment of immune cells. Plasminogen then participates in the remodeling phase where lack of plasminogen leads to a haltered resolution of the inflammatory phase and reduced activation of non-immune cells to undergo EMT, a process which is required for the formation of granulation tissue and re-epithelization. Finally, plasminogen also participates in the remodeling of extracellular matrix. As a consequence, plasminogen activates and enhances healing of acute and chronic wounds. In addition, by enhancing immune activation, plasminogen also activates the body’s own defense mechanisms against infections including infections by antibiotic-resistant bacteria.
Thus, by plasminogen treatment we enhance the body’s own capability to heal wounds and prevent and treat infections in a safe and effective way.