A novel human ex vivo skin model to study early local responses to burn injuries

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.

SH-29 and SK-119 Attenuates Air-Pollution Induced Damage by Activating Nrf2 in HaCaT Cells

“…The efficacy and safety of SH-29 and SK-119 were investigated in the well-established HaCaT keratinocyte cell line and in the ex vivo human skin organ culture systems [ 29 , 60 , 61 , 62 , 63 ]. Although the latter closely emulates the physical and biochemical properties of intact human tissue, it lacks the connection to the circulation, systemic inflammatory components, and the nervous system.…”

“…In order to further evaluate the compound, a preliminary local safety assessment was performed in the ex vivo human skin organ cultures. This system was used as a valid experimental system for both efficacy and safety assessment with good correlation to clinical data [ 62 , 63 , 64 , 65 ]. Three biomarkers were tested and were unaltered by both compounds: skin morphology (evaluated by H&E staining), epidermal viability (MTT), and by monitoring the level of IL-1α, suggesting that the molecules are safer for topical usage.…”

Recent Advances in Experimental Burn Models

“…Therefore, most radiation-inflicted injury models require laborious pilot experiments to determine the unique adjustments needed for each experimental setting. Furthermore, human or porcine ex vivo and in vitro skin models have been established to study the immediate local response to thermal burns or novel treatments [44,[49][50][51][52]73].…”

“…Animal models are still widely used, with rodents favored for mechanistic studies. However, human ex vivo models are gaining traction, with the advantage that they reduce and replace animal experiments and provide native skin tissue architecture to recapitulate important aspects of the human burn response [44,51,52,73].…”

Clinical significance of serum matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in the first phase of burn trauma evolution

“…After a severe burn injury, the wound healing response involves the dynamic interaction of many pathophysiological processes such as inflammation, proliferation, and tissue remodeling (1). The first phase consists of releasing a prolonged immune response (cytokines and chemokines in the endothelium) that activates proinflammatory effector cells at the site of injury and increases vasodilation and tissue edema (2). In early inflammation, increased levels of proinflammatory cytokines bring neutrophils and monocytes to the site (3).…”