Unveiling the impact of hypodermis on gene expression for advancing bioprinted full-thickness 3D skin models

• Published in: Communications biology 2024-11, Vol.7 (1), p.1437-13, Article 1437
• Main Authors: Avelino, Thayná M., Harb, Samarah V., Adamoski, Douglas, Oliveira, Larissa C. M., Horinouchi, Cintia D. S., Azevedo, Rafael J. de, Azoubel, Rafael A., Thomaz, Vanessa K., Batista, Fernanda A. H., d’Ávila, Marcos Akira, Granja, Pedro L., Figueira, Ana Carolina M.
• Format: Article
• Language: English
• Subjects: 13/106; 13/107; 14/19; 14/28; 3-D printers; 38/77; 38/91; 631/1647/767/2202; 631/61/2035; 96/63; Animal models; Biomedical and Life Sciences; Bioprinting - methods; Cell Differentiation; Dermis; Epidermis; Gene expression; Gene Expression Regulation; Humans; Hydration; Hydrogels; Immunofluorescence; Keratinocytes - metabolism; Laboratory animals; Life Sciences; Printing, Three-Dimensional; Scanning electron microscopy; Skin - metabolism; Skin diseases; Skin, Artificial; Tissue Engineering - methods; Tissue Scaffolds; Toxicology; Transcriptomes
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-07106-4

3D skin models have been explored as an alternative method to the use of animals in research and development. Usually, human skin equivalents comprise only epidermis or epidermis/dermis layers. Herein, we leverage 3D bioprinting technology to fabricate a full-thickness human skin equivalent with hypodermis (HSEH). The collagen hydrogel-based structure provides a mimetic environment for skin cells to adhere, proliferate and differentiate. The effective incorporation of the hypodermis layer is evidenced by scanning electron microscopy, immunofluorescence, and hematoxylin and eosin staining. The transcriptome results underscore the pivotal role of the hypodermis in orchestrating the genetic expression of a multitude of genes vital for skin functionality, including hydration, development and differentiation. Accordingly, we evidence the paramount significance of full-thickness human skin equivalents with hypodermis layer to provide an accurate in vitro platform for disease modeling and toxicology studies. We used 3D bioprinting to create a full-thickness human skin model with a hypodermis layer, offering an in vitro tool for disease and toxicology studies. This model replicates skin function and highlights the hypodermis’ role in tissue development.