The paper explores the progression from traditional two-dimensional cell cultures towards more complex systems including reconstructed human skin, 3D bioprinting, skin organoids and skin-on-chip technologies. According to the authors, these models better replicate the structure, extracellular matrix organisation and mechanical environment of ageing human skin. 

The review highlights how skin ageing is closely linked to dynamic remodelling of the extracellular matrix, including collagen degradation, elastic fibre disruption, inflammation, oxidative stress and changes in basement membrane stiffness. The authors suggest that advanced 3D systems may provide more physiologically relevant platforms for studying these processes than conventional monolayer cultures or animal models. 

The paper also discusses the growing role of microphysiological systems in anti-ageing drug development and cosmetic testing, particularly following restrictions on animal testing in several regions. Technologies such as skin-on-chip platforms were highlighted for their ability to simulate mechanical stress, vascularisation and inflammatory signalling associated with ageing skin. 

The authors conclude that next-generation in vitro skin models could improve understanding of skin ageing mechanisms and support development of more targeted regenerative and preventative strategies. However, they note that current systems still only partially replicate the complexity of human skin ageing in vivo.