One-Step Coaxial 3D Printing of Pre-Vascularized Skin Organoid Models with ADSC Microspheres for Enhanced Wound Healing.

ABSTRACT: Organoids are important tools for studying organ development, drug screening, and regenerative medicine, yet the absence of integrated vasculature limits their culture and translation. To address this, the PV-XOM strategy is proposed, which achieves one-step construction of pre-vascularized organoids through coaxial bioprinting: the inner phase uses temperature-responsive sacrificial material and endothelial cells to form hollow vascular channels, while the outer phase is a biomimetic hydrogel matrix containing organoid microspheres. Based on this framework, a pre-vascularized skin organoid model (PV-SOM) is established, in which the outer phase is loaded with adipose-derived stem cell (ADSC) microspheres and skin fibroblasts. In vitro, PV-SOM achieved rapid vascular closure and maturation; in vivo, it formed abundant neovessels in large skin defects, accelerated wound closure, and improved collagen remodeling. Proteomic analysis further revealed that ADSC microspheres activate the PI3K-AKT-mTOR pathway to regulate vascular formation across multiple stages. These findings show that PV-XOM offers an effective, scalable solution to the vascularization bottleneck of organoids with strong translational potential.

SUBMITTER: Wang K 

PROVIDER: S-EPMC12904007 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature