The article "Bioengineering methods for vascularizing organoids" by Peter N. Nwokoye and Oscar J. Abilez reviews the advancements in bioengineering strategies to address the critical limitation of lack of an integrated vascular network in organoids. Organoids, self-organizing 3D structures derived from stem cells, offer significant advantages in studying organ development, disease modeling, and therapeutic screening. However, their translational potential is hindered by the absence of a functional vasculature, which is essential for nutrient supply, waste removal, and maintaining tissue homeostasis. The review explores various bioengineering approaches to vascularize organoids, including co-culturing organoids with vascular cells, co-culturing lineage-specific organoids with vascular organoids, co-differentiating stem cells into organ-specific and vascular lineages, using organoid-on-a-chip technology, and 3D bioprinting. Each method is discussed in detail, highlighting its biological principles, strengths, limitations, and potential applications. Key points include: - **Co-culture with vascular cells**: Introducing endothelial cells (ECs) and supporting cell types encourages the self-assembly of vessel-like structures. - **Co-culture with vascular organoids**: Facilitates integration and promotes vascularization. - **Organoid co-differentiation**: Simultaneous differentiation of stem cells into organ-specific and vascular lineages. - **Organoid-on-a-chip (OOC)**: Integrates organoids into microfluidic devices to create perfused, vascularized systems. - **3D bioprinting**: Precisely deposits cells, biomaterials, and sacrificial inks to fabricate organoids with pre-defined vascular channels. The review also delves into the biological principles governing vascularization, such as the role of fluid shear stress, extracellular matrix (ECM) composition, and signaling pathways like VEGF-A, FGF-2, and Wnt. It emphasizes the importance of understanding the complex interplay between stem cell niches and vascular networks, and how these interactions influence organoid development and function. Additionally, the article discusses the use of scaffolds and hydrogels to support vascularization, including animal-derived and synthetic materials. It highlights the advantages and challenges of using decellularized extracellular matrices (dECMs) and the potential of human pluripotent stem cells (hPSCs) for creating vascularized organoids. Overall, the review underscores the rapid progress in bioengineering methods for vascularizing organoids and the potential of these advancements to enhance the physiological relevance and translational potential of organoid models in biomedical research and regenerative medicine.The article "Bioengineering methods for vascularizing organoids" by Peter N. Nwokoye and Oscar J. Abilez reviews the advancements in bioengineering strategies to address the critical limitation of lack of an integrated vascular network in organoids. Organoids, self-organizing 3D structures derived from stem cells, offer significant advantages in studying organ development, disease modeling, and therapeutic screening. However, their translational potential is hindered by the absence of a functional vasculature, which is essential for nutrient supply, waste removal, and maintaining tissue homeostasis. The review explores various bioengineering approaches to vascularize organoids, including co-culturing organoids with vascular cells, co-culturing lineage-specific organoids with vascular organoids, co-differentiating stem cells into organ-specific and vascular lineages, using organoid-on-a-chip technology, and 3D bioprinting. Each method is discussed in detail, highlighting its biological principles, strengths, limitations, and potential applications. Key points include: - **Co-culture with vascular cells**: Introducing endothelial cells (ECs) and supporting cell types encourages the self-assembly of vessel-like structures. - **Co-culture with vascular organoids**: Facilitates integration and promotes vascularization. - **Organoid co-differentiation**: Simultaneous differentiation of stem cells into organ-specific and vascular lineages. - **Organoid-on-a-chip (OOC)**: Integrates organoids into microfluidic devices to create perfused, vascularized systems. - **3D bioprinting**: Precisely deposits cells, biomaterials, and sacrificial inks to fabricate organoids with pre-defined vascular channels. The review also delves into the biological principles governing vascularization, such as the role of fluid shear stress, extracellular matrix (ECM) composition, and signaling pathways like VEGF-A, FGF-2, and Wnt. It emphasizes the importance of understanding the complex interplay between stem cell niches and vascular networks, and how these interactions influence organoid development and function. Additionally, the article discusses the use of scaffolds and hydrogels to support vascularization, including animal-derived and synthetic materials. It highlights the advantages and challenges of using decellularized extracellular matrices (dECMs) and the potential of human pluripotent stem cells (hPSCs) for creating vascularized organoids. Overall, the review underscores the rapid progress in bioengineering methods for vascularizing organoids and the potential of these advancements to enhance the physiological relevance and translational potential of organoid models in biomedical research and regenerative medicine.