Unveiling the Impact of Hypodermis on Gene Expression for Advancing Bioprinted Full-Thickness 3D Skin Models

3D skin models have been explored as analternative method to the use of animals inresearch and development. Usually, human skinequivalents comprise only epidermis orepidermis/dermis layers. Herein, we leveraged 3Dbioprinting technology to fabricate a full-thicknesshuman skin equivalent with hypodermis (HSEH).The collagen hydrogel-based structure provided amimetic environment for skin cells to adhere,proliferate and differentiate. The effectiveincorporation of the hypodermis layer wasevidenced by scanning electron microscopy,immunofluorescence, and hematoxylin and eosinstaining. The mRNA gene expression resultsunderscored the pivotal role of the hypodermis inorchestrating the genetic expression of a multitudeof genes vital for skin functionality, includinghydration, development and differentiation.Accordingly, we have evidenced the paramountsignificance of full-thickness human skinequivalents with hypodermis layer to provide anaccurate in vitro platform for disease modelingand toxicology studies.