3D skin models for 3R research: The potential of 3D reconstructed skin models to study skin barrier function

Abstract

The skin barrier is an important shield regulating the outside-in as well as inside-out penetration of water, nutrients, ions and environmental stimuli. We can distinguish four different barrier compartments: the physical, chemical, immunological and microbial skin barrier. Well-functioning of those is needed to protect our body from the environment. To better understand the function and the contribution of barrier dysfunction in skin diseases, 3D skin or epidermal models are a valuable tool for in vitro studies. In this review, we summarize the development and application of different skin models in skin barrier research. During the last years, enormous effort was made on optimizing these models to better mimic the in vivo composition of the skin, by fine-tuning cell culture media, culture conditions and including additional cells and tissue components. Thereby, in vitro barrier formation and function has been improved significantly. Moreover, in this review we point towards changes and chances for in vitro 3D skin models to be used for skin barrier research in the nearby future.

On the relevance of an in vitro reconstructed human epidermis model for drug screening in atopic dermatitis

“…3D in vitro skin models range from simple RHE to complex full‐skin equivalents integrating immune cells or microfluidic platforms. Complexity is relevant when studying cell‐type interactions, particularly interactions with the immune system . However, complex models may present biological variations and higher production costs.…”

Characterization of human skin equivalents developed at body's core and surface temperatures

“…The main physical barrier of NHS and HSEs is formed by corneocytes, corneodesmosomes, tight junctions, and the lipid matrix (Basler et al, ; Haftek, ; Niehues et al, ). However, in this study, the lipid matrix was characterized, which is the only continuous pathway through the SC, and thereby regarded pivotal for the outside‐in permeability barrier.…”

“…Tissue engineered human skin equivalents (HSEs) mimic many properties of native human skin (NHS). However, several aspects of in vitro tissue reconstruction need to be studied and optimized to further increase the resemblance to NHS, to understand the underlying biology, and to improve in vitro–in vivo correlations (Boyce, ; Gordon et al, ; Niehues et al, ; Planz, Lehr, & Windbergs, ). The main barrier of the skin resides in the uppermost layer of the epidermis, which is termed the stratum corneum (SC; Proksch, Brandner, & Jensen, ).…”

Rapid expansion in the WAVE bioreactor of clinical scale cells for tumor immunotherapy

“…Another popular culture technique, three-dimensional (3D) cell culture, could mimic in vivo conditions, such as dynamic interaction between tumor or immune compartments, demonstrating more organotypic properties than static cultures. 44 3D cell culture is widely used in laboratory investigations, including in the research on cell differentiation, 5 stem-cell-based regenerative medicine, 45 skin, tissue, or organoid regeneration, [47][48][49] tumor microenvironment, and drug susceptibility. 46,50 Although 3D culture has proven to be superior as compared to its traditional static counterparts; the high cost, challenging setup, low reproducibility, and timeconsumption have limited the utilization on clinical scale-up cell immunotherapy.…”