Biodegradable and hollowed micro-scaffolds for improved modular assembly-based tissue engineering: Design, 3D fabrication, and feasibility in randomly packed perfusion culture

A novel biodegradable micro-scaffold with intersecting hollow channels was designed as tissue elements to address the main challenges in current modular assembly-based tissue engineering-the lack of lacking rigid structures to sustain in vivo-like flow conditions, and delicate design to facilitate mass transfer to the cultured cells towards scaling upto high cell-density and functional tissues. Such scaffolds, having around 60% porosity, were successfully fabricated from poly-ε-caprolactone via selective laser sintering. Pressure drop measurements clearly showed better perfusion of culture medium throughout those micro-scaffolds compared to similar cylindrical scaffolds without hollows. After 14 days of perfusion culture of micro-scaffolds seeded with human hepatoma Hep G2 cells and randomly packed in a bioreactor, the hollow structures were well retained as flow channels, contributing to remarkably enhanced cellular growth, glucose consumption, albumin production, cell viability and homogenous immobilization. These results demonstrate that the proposed micro-scaffolds ensure better mass transfer in randomly packed perfusion culture, thus greatly increasing the feasibility of modular assembly-based methods to engineer large high cell-density and functional tissues.