Functional cell-laden alginate scaffolds consisting of core/shell struts for tissue regeneration.

We report an innovative cell-dispensing process using a three-axis robot system coupled with a micro-core/shell nozzle and an aerosol cross-linking process to achieve controlled mechanical properties and high cell viability of porous cell-laden alginate scaffolds. The scaffolds were fabricated into layer-by-layer struts, which were used to design the pore structure. The struts consisted of a core/shell region; a low weight fraction of alginate and cells (MC3T3-E1) was injected in the shell region to efficiently exchange nutrients and metabolic wastes, while a high weight fraction of alginate without cells was deposited in the core region to improve the mechanical properties of the cell-laden scaffold. After 10 days of cell culture, the cell viability (95%) in the shell region improved significantly compared to 70% for the cells homogeneously distributed in the struts, and the mechanical properties were enhanced from 1.4 to 15.7 kPa. Stained nuclei and F-actin images showed that the laden cells proliferated well on the functional hydrogel scaffold after 20 days of cell culture, indicating that the cells concentrated in the shell region of the struts survived and increased their metabolic functions during several incubation periods compared to the standard cell-laden scaffold. This innovative cell-dispensing technique represents a promising fabrication tool for obtaining bottom-up scaffolds for various tissue regenerations.