Development of a controlled ex vivo human skin platform for quantitative evaluation of age-related functional biomarkers following application of topical treatments.

An ex vivo human skin explant platform was developed using freshly acquired tissues from donors of varying ages and Fitzpatrick skin types to enable reproducible photodamage assessment.

• The platform accommodates donors of varying ages and Fitzpatrick skin types, addressing diversity limitations of prior preclinical models.
• Standardized UVA and UVB doses were applied to induce reproducible photodamage.
• The model was designed to enable assessment of both preventative and reparative effects of topical treatments.
• The platform was designed to capture the full architecture of human skin, improving upon models that 'fail to capture the full architecture of human skin.'

ND-ZnO and NAC reduced levels of p16^INK4a and p53, key biomarkers of cellular senescence, in the ex vivo skin platform.

• p16^INK4a and p53 were used as key biomarkers measuring cellular senescence.
• Both ND-ZnO and NAC treatments were associated with reduced levels of these senescence biomarkers.
• Targeting cellular senescence was framed as a promising approach to slow visible skin aging and promote tissue repair.
• Histological analysis confirmed the molecular findings.

ND-ZnO and exosomes lowered IL-1β expression, a biomarker of inflammation, in the ex vivo platform.

• IL-1β was used as a biomarker measuring inflammation.
• Both ND-ZnO and exosomes were associated with reduced IL-1β expression.
• This finding was distinct from the senescence biomarker reductions, which were associated with ND-ZnO and NAC rather than exosomes.
• Histological analysis confirmed reduced inflammatory features in treated skins.

Histological analysis confirmed that ND-ZnO-treated skins preserved epidermal structure, reduced inflammatory features, and maintained dermal collagen organization.

• Preserved epidermal structure was observed in ND-ZnO-treated skins.
• Reduced inflammatory features were noted histologically in ND-ZnO-treated skins.
• Maintained dermal collagen organization was observed in ND-ZnO-treated skins.
• Histological findings were consistent with the molecular biomarker results.

A four-week single-patient case study using the ND-ZnO formulation showed visible improvements in redness, pigmentation, and texture.

• The case study was conducted over four weeks in a single patient.
• The same ND-ZnO formulation used in ex vivo experiments was applied.
• Visible improvements were observed in redness, pigmentation, and texture.
• Clinical observations aligned with the molecular and histological changes seen ex vivo.
• The authors noted this was a 'single-patient case study,' indicating limited sample size.

Most existing preclinical models fail to capture the full architecture of human skin or accommodate diverse skin types, limiting their translational relevance.

• This limitation motivated the development of the new ex vivo platform.
• The new platform specifically addressed inclusion of donors of varying ages and Fitzpatrick skin types.
• Translational relevance was identified as a key gap in existing models.
• The authors described the platform as 'a more inclusive, human-relevant model.'

The ex vivo platform has the potential to be used as a more inclusive, human-relevant model for evaluating and quantifying anti-aging efficacies of topical treatments across diverse skin types and age groups.

• The platform supports evaluation across diverse skin types and age groups.
• Both preventative and reparative effects of topical treatments can be assessed.
• The model uses freshly acquired human tissues, enhancing biological relevance.
• Quantitative evaluation of age-related functional biomarkers is enabled by the platform.