Bioengineering Human Full Thickness Skin Equivalents to Investigate the Effects of Skin Ageing on Pigmentation

The skin is the largest organ in the human body, serving critical functions in water homeostasis, thermoregulation, and protection against environmental stressors. However, as we age, both the structure and function of skin become compromised due to complex and multifactorial underlying processes. Among the many visible signs of skin aging, pigmentary changes are common, yet the mechanisms driving these alterations remain poorly understood. Moreover, as the global population of elderly individuals increases and ethnic diversity in skin research remains underrepresented, there is a pressing need to explore more advanced models that more accurately reflect the complexities of skin ageing and pigmentation across different demographics. While melanocytes have been included in 3D in vitro skin models using intrinsically aged cells, the existing models are limited in scope and require optimisation for greater complexity.

The objective of this project was to construct novel bioengineered ageing pigmented 3D in vitro full thickness human skin equivalents, developed using AlvetexÒ technology, to investigate the effects of ageing on pigmentation. It was hypothesised that melanocytes would be successfully integrated into the ageing skin equivalents to produce pigmented models of aged skin. Moreover, it was hypothesised that there would be phenotypic effects on pigmentation in the ageing skin models, including an overall reduction in pigmentation and the appearance of age spots. Melanocytes were incorporated into these models, which were constructed using age-matched, intrinsically aged fibroblasts and keratinocytes. Phenotypic changes in pigmentation, including a decrease in gross pigmentation and the development of hyperpigmented lesions, were observed and quantitatively validated, with findings comparable to those seen in native human skin. This innovative model offers a promising platform for advancing our understanding of skin ageing and pigmentation and holds potential for industrial applications in dermatological research.