A Bioengineered Human Skin Tissue for the Treatment of Infected Wounds

Abstract

Complex skin defects resulting from acute skin trauma and chronic, nonhealing wounds are life-threatening injuries. Infection is one of the most common obstacles to the healing of these types of wounds. Host defense peptides (HDPs) possessing a broad spectrum of activity against microorganisms and serving as innate immune modulators have emerged as potential treatment strategies for infected wounds. The increase in multidrug-resistant clinical bacterial isolates highlights the need for new and innovative anti-infective therapies for the treatment of both acute and chronic skin wounds. To address the critical need for new therapeutic options to reduce infection and improve wound healing, a bioengineered skin substitute (BSS) tissue has been created to act as an anti-infective living human skin tissue that provides enhanced expression of the endogenous HDP, cathelicidin. To generate a BSS exhibiting these antimicrobial properties, the clinically tested NIKS progenitor cells were employed to provide a source of genetically uniform, nontumorigenic, pathogen-free human keratinocytes that are amenable to genetic engineering using nonviral means. Pathogenic bacterial strains are increasingly developing antibiotic resistance, thereby forcing the clinician to use potent antibiotics with deleterious effects on keratinocyte viability and migration. Therefore, an urgent need exists for new wound therapies that can circumvent many of the problems associated with current antibiotic treatments. Enhanced expression of cathelicidin in a genetically engineered human BSS has been shown to inhibit the bacterial growth of a multidrug-resistant clinical strain of Acinetobacter baumannii in vivo, creating a new and innovative therapeutic option for combating these debilitating wound infections while also promoting healing.