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Atopic dermatitis (AD), a chronic inflammatory disease with severe itching, has complex pathogenesis, making prognosis prediction difficult. Thus, developing AD models reflecting its features is crucial. Based on public AD patient scRNA-seq data, we identified: (1) COL6A5+ fibroblasts in patient tissues, (2) itch-related interactions between cells and dorsal root ganglia (DRG), and (3) overexpression of hypoxia-related factors. A gelatin-based in-situ crosslinking hydrogel AD model was designed to replicate these tissue characteristics. The 3D cell culture system, encapsulating cells in the hydrogel, supports cell survival/growth under hypoxic conditions (pO2 < 5%), with upregulated hypoxia-related genes. This hydrogel-based skin model reconstructs the AD microenvironment by inducing immune responses/chronic hypoxia via IL-4 treatment and oxygen control. It analyzes itch factor overexpression, evaluates drug responses, and assesses hypoxia/immune-related gene upregulation. This platform serves as a potential preclinical model for drug screening and basic research.
Summary
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by severe itching, and its complex pathological mechanisms make the development of disease models and drug screening challenging. Recently, a study published in Bioactive Materials developed an engineered AD model based on gelatin hydrogel, successfully simulating the hypoxic microenvironment in patient skin tissue.
The research team first analyzed public single-cell RNA sequencing data and found that fibroblasts with high expression of COL6A5 are present in the skin of AD patients. These fibroblasts closely interact with dorsal root ganglia and are accompanied by significant upregulation of hypoxia-related genes. Based on these characteristics, the researchers designed an in situ crosslinkable gelatin hydrogel system that, by regulating oxygen concentration and IL-4 stimulation, recreates the chronic hypoxia and immune response conditions of AD in a three-dimensional culture environment.This model not only supports long-term cell survival and growth but also induces high expression of itch-related factors (such as periostin) and successfully simulates functional interactions between fibroblasts and sensory neurons. Further experiments demonstrated that this system can be used to evaluate the therapeutic response to drugs (such as dexamethasone), showing its potential as a preclinical drug screening platform. This study provides a new biomimetic model for mechanism research and precision therapy of AD, and in the future, by introducing more cell types and cytokines, it is expected to construct an integrated experimental system that more closely resembles human pathological conditions.
References:
DOI:10.1016/j.bioactmat.2025.12.045
