Advances in the Biofabrication of 3D Skin in vitro: Healthy and Pathological Models

Abstract

The relevance for in vitro three-dimensional (3D) tissue culture of skin has been present for almost a century. From using skin biopsies in organ culture, to vascularized organotypic full-thickness reconstructed human skin equivalents, in vitro tissue regeneration of 3D skin has reached a golden era. However, the reconstruction of 3D skin still has room to grow and develop. The need for reproducible methodology, physiological structures and tissue architecture, and perfusable vasculature are only recently becoming a reality, though the addition of more complex structures such as glands and tactile corpuscles require advanced technologies. In this review, we will discuss the current methodology for biofabrication of 3D skin models and highlight the advantages and disadvantages of the existing systems as well as emphasize how new techniques can aid in the production of a truly physiologically relevant skin construct for preclinical innovation.

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

“…However, one must keep in mind that 3D skin models possess weaker barrier properties compared to the native skin. More advanced and relevant 3D skin models are developed that include immune cells, melanocytes, sebocytes, and endothelial cells, stimuli for lipid synthesis [261], and cultivation conditions closer to the real-life situation [262]; hence a complete immune system [263], vascularization [264], and barrier properties similar to human skin are the main elements that current models are lacking [265]. Skin surface lipids (e.g., sebum) were not considered to date in 3D skin models utilized for PMtesting.…”

Human skin models: From healthy to disease‐mimetic systems; characteristics and applications

“…The assessment of drug effects on skin disease is clearly essential but the availability of excised human diseased skin is limited, mainly due to the increasing regulatory restrictions on the use of animals and humans. cutaneous wounds, and skin cancer (melanoma) (Abd et al, 2016;Amelian et al, 2017;Randall et al, 2018;Yun et al, 2018).…”

“…VanGele et al, 2011).The complexity of the skin mimetic models has been increasing to obtain models comprising simple or more complex cell cultures.Single-cell or multicell-type two-dimensional (2D) cultures, in which cells are grown as a monolayer on solid flat surfaces, such as polystyrene or glass, are some of the most often used, cell-based approaches due to their relative simplicity and cost-effectiveness(Randall, Jüngel, Rimann, & Wuertz-Kozak, 2018).…”

Vascularised human skin equivalents as a novel in vitro model of skin fibrosis and platform for testing of antifibrotic drugs

“…Although studies in 2D cell culture systems have provided important insights into cellular responses of individual cell types to defined stimuli, they have several important limitations: they cannot mimic (patho)physiologically relevant cell–matrix interactions, interactions between different cell types, presence of nutrient gradients and signalling pathways related to these processes 3–5. Moreover, culture of adherent cell types on plastic surfaces exposes them to an unphysiologically stiff environment, which alters central cellular responses such as response to cytokines, organisation of the cytoskeleton, migration and proliferation 6 7. Cellular responses in 2D culture models may thus not always reliably predict the pathological processes in fibrotic tissues.…”