Enhancing Viability in Static and Perfused 3D Tissue Constructs Using Sacrificial Gelatin Microparticles

Current limitations in engineered tissues arise from the inability to provide sufficient nutrients to cells deep within constructs, restricting their viability. This study focuses on enhancing diffusion by creating a microporous microenvironment using gelatin microparticles within collagen scaffolds. By leveraging the FRESH (Freeform Reversible Embedding of Suspended Hydrogels) 3D bioprinting technique, gelatin microparticles are utilized both as a support material and as a thermoresponsive porogen to establish interconnected pores. The results indicate that scaffolds with 75% porosity significantly increase diffusion rates and cell viability, extending beyond the conventional ∼200 μm limit. Additionally, integrating vascular-like channels with porous scaffolds and applying perfusion improved nutrient transport, leading to enhanced cell survival in larger constructs. This combination of microporosity and perfusion represents a promising approach to create thicker tissues without necrotic regions, potentially paving the way for scalable tissue engineering applications. The findings suggest that optimizing pore sizes and scaffold perfusion can bridge the gap between rapid tissue formation and slower vascularization processes, enabling the future development of functional tissue constructs at clinically relevant scales.