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

A multifunctional vascular bed platform is created using coaxial 3D printing, allowing the one‐step integration of organoid microspheres with perfusable vascular structures. This strategy enables rapid and functional vascularization of organoids to support tissue repair and vascularization, providing a scalable and translationally promising approach for advancing organ regeneration therapies. 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. A multifunctional vascular bed platform is created using coaxial 3D printing, allowing the one-step integration of organoid microspheres with perfusable vascular structures. This strategy enables rapid and functional vascularization of organoids to support tissue repair and vascularization, providing a scalable and translationally promising approach for advancing organ regeneration therapies. 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. Advanced Science, EarlyView.