Wound-Healing Peptides for Treatment of Chronic Diabetic Foot Ulcers and Other Infected Skin Injuries

Abstract

As the incidence of diabetes continues to increase in the western world, the prevalence of chronic wounds related to this condition continues to be a major focus of wound care research. Additionally, over 50% of chronic wounds exhibit signs and symptoms that are consistent with localized bacterial biofilms underlying severe infections that contribute to tissue destruction, delayed wound-healing and other serious complications. Most current biomedical approaches for advanced wound care aim at providing antimicrobial protection to the open wound together with a matrix scaffold (often collagen-based) to boost reestablishment of the skin tissue. Therefore, the present review is focused on the efforts that have been made over the past years to find peptides possessing wound-healing properties, towards the development of new and effective wound care treatments for diabetic foot ulcers and other skin and soft tissue infections.

The discovery and development of topical medicines for wound healing

“…Additionally, AMP drug development has been hindered by their susceptibility to protease activity and their high levels of cytotoxity [96,97]. Despite the awareness of resistance development using endogenous AMPs, several AMPs are considered potential drug candidates aimed toward wound healing [98]. Pexiganan has a long and troubled drug development history.…”

Peptide-Based Drugs and Drug Delivery Systems

“…An increasing number of papers in recent literature concerns the potential interest of AMPs and other peptides in tackling problems related to wound healing/regeneration [ 6 ]. Gomes et al [ 7 ] have focused on peptides whose wound-healing effects may find application in the topical treatment of diabetic foot ulcers, as well as other skin and soft tissue infections, holding great promise for development of novel strategies for treatment of chronically infected wounds. The authors described the applications of several AMPs of human and amphibian origin, which can influence different mechanisms of the wound-healing process, such as inflammation, epithelialization, tissue granulation and remodeling.…”

Clarithromycin Enhances the Antibacterial Activity and Wound Healing Capacity in Type 2 Diabetes Mellitus by Increasing LL-37 Load on Neutrophil Extracellular Traps

“…Taking into account the abovementioned data together with the increasing evidence that LL-37 promotes wound healing ( 27 , 29 ), we sought to investigate whether LL-37-bearing diabetic NETs are implicated in wound healing process, as well as the effect of clarithromycin.…”

“…Though, whether this immunomodulatory role of such a widely used antibiotic could be utilized against susceptibility to infections in T2D is unknown. In addition, several in vitro and in vivo studies suggest that LL-37 is also associated with wound healing by promoting re-epithelialization and vascularization ( 27 – 29 ). However, whether LL-37 could be beneficial against impaired wound healing in T2D is still under investigation.…”