Abstract

Burn injuries initiate numerous processes such as heat shock response, inflammation and tissue regeneration. Reliable burn models are needed to elucidate the exact sequence of local events to be able to better predict when local inflammation triggers systemic inflammatory processes. In contrast to other ex vivo skin culture approaches, we used fresh abdominal skin explants to introduce contact burn injuries. Histological and ultrastructural analyses confirmed a partial-thickness burn pathology. Gene expression patterns and cytokine production profiles of key mediators of the local inflammation, heat shock response, and tissue regeneration were analyzed for 24 h after burn injury. We found significantly increased expression of factors involved in tissue regeneration and inflammation soon after burn injury. To investigate purely inflammation-mediated reactions we injected lipopolysaccharide into the dermis. In comparison to burn injury, lipopolysaccharide injection initiated an inflammatory response while expression patterns of heat shock and tissue regeneration genes were unaffected for the duration of the experiment. This novel ex vivo human skin model is suitable to study the local, early responses to skin injuries such as burns while maintaining an intact overall tissue structure and it gives valuable insights into local mechanisms at the very beginning of the wound healing process after burn injuries.

Highlights

  • Burn injuries have been ­described[31], but due to anatomical and physiological differences, it is difficult to directly translate findings from animal models to the clinical ­situation[32]

  • We found a significant up-regulation of the pro-inflammatory cytokine IL1B (Fig. 6a) and a trend for increased expression for IL6 and CXCL8 (Fig. 6b,c) in response to LPS compared with the control site, where a sterile NaCl solution was injected into the dermis

  • Burn injuries are known to trigger a complex cascade of wound healing mechanisms, and with increasing size and depth of the burn injury local responses may result in systemic effects such as systemic inflammatory response syndrome (SIRS) eventually leading to fatal ­complications[1,2,3,4,44]

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Summary

Introduction

Burn injuries have been ­described[31], but due to anatomical and physiological differences, it is difficult to directly translate findings from animal models to the clinical ­situation[32]. Burn injuries are induced on the fresh e­ xplants[42] and local processes can be monitored for up to 36 h after resection. We characterized this ex vivo model of burn injuries on the histological as well as on the molecular level. Inflammatory and regenerative responses to burn injury were monitored over a period of 24 h while leaving the normal skin architecture intact, resulting in local time-dependent gene expression and cytokine production profiles. Gene expression analyses were performed to elucidate the effect of the intradermal application of LPS in comparison to the injection of a sterile NaCl solution that served as a control for the injection trauma

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