Bioprinted Recombinant Human-Collagen-Based In Vitro Skin Models for Assessing Effects of Nano-ZnO on Dermis

Collagen types I and III are primary structural proteins that maintain human skin integrity, and their ratio is disrupted during aging. In this study, we developed a biomimetic 3D skin model with vascularization potential to evaluate the effects of nano-zinc oxide (nano-ZnO) in a physiologically relevant context. The model used methacrylated recombinant human collagen (RHC-MA) bioinks with tunable collagen I/III ratios that mimic the skin of children and adults. The bioinks exhibited excellent printability and mechanical properties that enabled the 3D bioprinting of full-thickness skin products, including dermal layers with human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs), as well as epidermal layers with keratinocytes (KCs). The model recapitulated native skin architecture, and key markers such as keratin 10 (K10), keratin 14 (K14), and cluster of differentiation 31 (CD31) were determined. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that nano-ZnO significantly modulated genes associated with apoptosis, inflammation, and oxidative stress in skin cells.