The role of cultured autologous bilayered skin substitutes as epithelial stem cell niches after grafting: A systematic review of clinical studies

Abstract

To ensure graft persistence and thus to permanently restore the epithelial barrier function after grafting, bilayered tissue-engineered skin substitutes must be reconstructed in a way that favors the formation of an epithelial stem cell niche. It is however unclear what culture and production conditions, or combination thereof, are the most conducive to the establishment of a microenvironment that would be able to regulate epithelial stem cell quiescence and activity to appropriately satisfy the lifelong demand for differentiated cells. To address this issue, we undertook a systematic review of original clinical studies or case reports describing autologous tissue-engineered bilayered skin substitutes grafted in humans in the 25 years-span between August 1993 and August 2018. In total, we included 16 articles describing nine types of autologous bilayered skin substitutes. We examined four culture and production factors; keratinocyte seeding density, substitute scaffold type, whether serum or a serum replacement product was used to culture keratinocytes, and whether or not and what type of feeder layer was used to culture keratinocytes. Taken together, the data extracted from these 16 studies suggest that there are multiple combinations of culture and production factors that could result in the formation of a de novo epithelial stem cell niche in a bilamellar skin substitute.

Keywords

• Artificial skin
• Culture techniques
• Skin grafts
• Tissue engineering
• Transplantation
• Wound healing