(1) Title Engineered Atopic Dermatitis Models: Recreating Hypoxic Conditions in the AD Microenvironment

(2) Research Highlights This work designs an in-situ crosslinkable gelatin-based hydrogel model. Single-cell RNA sequencing analysis was used to verify key features of AD tissues (including COL6A5+ fibroblast expression, itch-associated neural interactions and overexpression of hypoxia factors). On this basis, a 3D culture system that mimics the hypoxic microenvironment of AD was established. By regulating oxygen concentration and IL-4 stimulation, this model successfully recapitulates chronic hypoxia, immune responses and the expression of itch mediators in AD, offering a new platform for AD mechanistic research and drug screening.

(3) Innovations ① Targeting hypoxia mechanisms: For the first time, core features of the hypoxic microenvironment in AD tissues (e.g., hypoxic conditions with pO₂ < 5%) are integrated into hydrogel models; ② Multidimensional simulation: Combined with cellular interactions, immune stimulation (IL-4) and hypoxic conditions, it simultaneously recapitulates itch, inflammation and the pathological microenvironment of AD; ③ Dynamic responsiveness: The model enables real-time monitoring of gene expression (e.g., hypoxia-related genes) and the effects of drug intervention, supporting in-depth mechanistic exploration.

(4) Biomedical Applications of the Material Disease modeling: Serving as an in vitro platform mimicking the pathological microenvironment of AD to replace animal models for investigating hypoxia, immunity and neural interaction mechanisms; Drug development: Applied in high-throughput screening of candidate drugs targeting itch mediators (e.g., neuromediators) or hypoxia pathways (e.g., HIF-1α); Basic research: Elucidating the roles of the fibroblast–immune cell–neuron network in AD to facilitate the design of precision therapeutic strategies.

(5) Extended Research Directions ① Multicellular co-culture: Introducing embedded co-culture systems of keratinocytes and immune cells to simulate the dynamics at the epidermal–dermal interface in AD; ② Microfluidic integration: Combining chip technology to achieve oxygen gradient control and cell migration analysis for improved microenvironment authenticity; ③ Cross-disease expansion: Adapting the system to develop models for other hypoxia-associated skin disorders (such as psoriasis) or chronic wounds.

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