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. The global $12.8 bn advanced wound care market is driven by an ageing population and rising incidence of ailments such as diabetes.
Wound healing is one of the most complex biological processes in the human body. After an injury occurs, several biological pathways are immediately activated and synchronized and involve many different cell types. This occurs in three partially overlapping and sequential phases, the inflammatory, proliferative, and remodeling phase.
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).
An error in any stage of this complex process can lead to chronic wounds, i.e. wounds that do not heal within the expected time, usually 4 weeks.
Physiological factors such as old age, impaired blood flow and diabetes can lead to an increased risk of chronic wounds in particular. Plasminogen has the potential to overcome impaired healing by enhancing the body's natural healing mechanisms.