Optimization of an ex vivo wound healing model in the adult human skin: Functional evaluation using photodynamic therapy
2015
Limited utility of in vitro tests and animal models of human repair, create a
demand for alternative models of cutaneous healing capable of functional testing.
The adult human skin Wound Healing Organ Culture (WHOC) provides a useful model,
to study repair and enable evaluation of therapies such as the photodynamic
therapy (PDT). Thus, the aim here was to identify the optimal WHOC model and to
evaluate the role of PDT in repair. Wound geometry, system of support, and growth
media, cellular and matrix biomarkers were investigated in WHOC models.
Subsequently, cellular activity, extracellular matrix remodeling, and oxidative
stress plus gene and protein levels of makers of wound repair measured the effect
of PDT on the optimized WHOC. WHOCs embedded in collagen and supplemented DMEM
were better organized showing stratified epidermis and compact dermis with
developing neo-epidermis. Post-PDT, the advancing reepithelialization tongue was
3.5 folds longer, and was highly proliferative with CK-14 plus p16 increased
(p?0.05) compared to controls. The neo-epidermis was fully differentiated
forming neo-collagen. Proliferating nuclear antigen, p16, COLI, COLIII, MMP3,
MMP19, and ?-SMA were significantly more expressed (p?0.05) in dermis
surrounding the healing wound. In conclusion, an optimal model of WHOC treated
with PDT shows increased reepithelialization and extracellular matrix
reconstruction and remodeling, supporting evidence toward development of an
optimal ex vivo wound healing model.
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