Organoids are three-dimensional clusters of stem cells that serve as valuable models for studying organ development and disease. However, their effectiveness is limited because they can form a necrotic core due to lack of nutrients and oxygen. This study looks at nature-inspired methods to improve organoid survival through vascularization and structural changes. First, we compared split organoids to intact ones. We found that splitting increases surface area and improves media flow, which helps reduce hypoxic stress and cell death. Bulk RNA sequencing showed that split organoids had lower expression of pro-apoptotic and stress-related genes. To further address diffusion issues, we explored using plant blood vessel structures by removing the cells from spinach leaves and embedding them in alginate-gelatin hydrogels. Perfusion tests with dye injection showed 64.3% central coverage, confirming that plant-based scaffolds can effectively transport nutrients. These findings suggest that adding vascular-like networks to organoid systems can greatly enhance viability, scalability, and biological relevance. This opens up new possibilities for personalized medicine, regenerative therapies, and modeling neurological diseases.
Abstract Organoids are three-dimensional clusters of stem cells that serve as valuable models for studying organ development and disease. However, their effectiveness is limited because [...]