Improved epidermal barrier formation in human skin models by chitosan modulated dermal matrices.
Full thickness human skin models (FTMs) contain an epidermal and a dermal equivalent. The latter is composed of a collagen dermal matrix which harbours fibroblasts. Current epidermal barrier properties of FTMs do not fully resemble that of native human skin (NHS), which makes these human skin models less suitable for barrier related studies. To further enhance the resemblance of NHS for epidermal morphogenesis and barrier formation, we modulated the collagen dermal matrix with the biocompatible polymer chitosan. Herein, we report that these collagen-chitosan FTMs (CC-FTMs) possess a well-organized epidermis and maintain both the early and late differentiation programs as in FTMs. Distinctively, the epidermal cell activation is reduced in CC-FTMs to levels observed in NHS. Dermal-epidermal interactions are functional in both FTM types, based on the formation of the basement membrane. Evaluation of the barrier structure by the organization of the extracellular lipid matrix of the stratum corneum revealed an elongated repeat distance of the long periodicity phase. The ceramide composition exhibited a higher resemblance of the NHS, based on the carbon chain-length distribution and subclass profile. The inside-out barrier functionality indicated by the transepidermal water loss is significantly improved in the CC-FTMs. The expression of epidermal barrier lipid processing enzymes is marginally affected, although more restricted to a single granular layer. The novel CC-FTM resembles the NHS more closely, which makes them a promising tool for epidermal barrier related studies.
Department of Dermatology, Leiden University Medical Centre, Leiden, the Netherlands.
Arnout
A
Mieremet
Department of Dermatology, Leiden University Medical Centre, Leiden, the Netherlands.
Marion
M
Rietveld
Division of Drug Delivery Technology, Leiden Academic Center for Drug Research, Leiden University, Leiden, the Netherlands.
Samira
S
Absalah
Division of Drug Delivery Technology, Leiden Academic Center for Drug Research, Leiden University, Leiden, the Netherlands.
Jeroen
J
van Smeden
Division of Drug Delivery Technology, Leiden Academic Center for Drug Research, Leiden University, Leiden, the Netherlands.
Joke A
JA
Bouwstra
Department of Dermatology, Leiden University Medical Centre, Leiden, the Netherlands.
Abdoelwaheb
A
El Ghalbzouri
D001485:Basement Membrane / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D048271:Chitosan / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D017768:Skin, Artificial
D003094:Collagen; D048271:Chitosan