Engineering a Halloysite Nanotube-Enhanced Hydrogel 3D Skin Model for Modulated Inflammation and Accelerated Wound Healing

This study introduces a hybrid collagen/alginate/hyaluronic acid hydrogel reinforced with halloysite nanotubes (HNTs) to replicate the dermal microenvironment for 3D skin modeling and wound repair. Incorporating 1 µg mL⁻¹ HNTs improved fibroblast proliferation, keratinocyte differentiation, and matrix stability while reducing degradation and swelling. RNA-seq analyses revealed activation of NF-κB, IL-17, and JAK-STAT pathways, reproducing inflammatory signatures of psoriasis. In vivo experiments in a murine model demonstrated accelerated epithelialization, enhanced collagen deposition, and increased CD34 and IL-17A expression in the HNT hydrogel group. The system provides a robust, biomimetic 3D platform for studying inflammatory skin biology and testing therapeutics.