Abstract: BACKGROUND: Constructing an effective vascular network is crucial for the successful regeneration of large-volume tissues and organs. Currently, vascular network design methods predominantly rely on predefined geometric patterns, making them inadequate to meet the metabolic demands of engineered tissues with diverse material properties and complex morphologies. Existing hierarchical vascular networks suffer from insufficient diffusion coverage and low nutrient supply rates due to their hierarchical rules.
OBJECTIVE: To propose a vascular network model design method based on developmental biomimetic principles, aiming to automatically generate customized voxel vascular network structures tailored to the metabolically active distance of target tissues.
METHODS: The method integrated voxelization techniques to simulate biological behaviors of vascular endothelial cells, such as migration and aggregation. Diffusion experiments were conducted on gel materials, and Fick’s law was applied to fit experimental data, establishing a rapid computational metabolism-diffusion model. Leveraging this model, the metabolically active distance was utilized to rapidly evaluate nutrient supply status and delineate low-nutrient regions. This process enabled a dynamic optimization mimicking vascular development to iteratively refine the vascular network until the predefined algorithm-set nutrient supply rate threshold was achieved.
RESULTS AND CONCLUSION: Compared with traditional hierarchical design methods, the proposed developmental biomimetic vascular network design demonstrated a 25.53% improvement in both nutrient-sufficient volume and nutrient contribution per unit volume within GelMA hydrogel-based cuboidal tissue constructs. This approach successfully generated nutrient-sufficient vascular network voxel models for complex-shaped engineered tissues and organs (e.g., renal-shaped and alveolar-shaped), validating its advantages in balancing structural adaptability with metabolic efficiency. The study provides a novel technical pathway for designing vascular networks in large-volume engineered tissues and anatomically complex organs.

Key words: biomimetic vascular network structure, engineered organ design, voxel-based design, generative algorithms, vascular network design, tissue repair, organ manufacturing, 3D bioprinting