Proteases and the diabetic foot syndrome: Mechanisms and therapeutic implications

Abstract

The long duration of treatment as well as high costs to treat Wagner stage 2-4 of diabetic foot ulcers make it imperative to employ effective programs that prevent wounds from developing and accelerate healing rates once wounds occur (120). Most diabetic ulcerations can be prevented by educating and informing patients (120-127). Once a wound develops, ∼70% of neuropathic foot lesions in diabetic patients can achieve healing by structured and stage-related therapy (off loading) and removing the barriers to natural healing by employing the concepts of wound bed preparation (debridement, control of infection/ inflammation, proper moisture balance, and care of the epidermal edge) (128-131). When more advanced adjuvant therapies are needed to promote healing, the therapies employed should be based on correcting the molecular defects that have been identified in chronic wounds, such as increasing the levels of biologically active growth factors (106,132-135) and reducing elevated levels of proteases (22,95,98,101,120, 134,136-138). Advanced adjuvant therapies employing autologous platelet extracts, recombinant growth factors, protease inhibitors, dressings that reduce protease activities, and bioengineered skin substitutes are currently available. Future studies will need to evaluate if combinations of advanced adjuvant therapies are beneficial in especially hard to heal diabetic wounds.