Rapid prototyping of a hybrid hierarchical polyurethane-cell/hydrogel construct for regenerative medicine

• We create a hybrid hierarchical polyurethane-cell/Hydrogel construct.
• Both synthetic and natural polymers have been used for the cell accommodation and growth.
• Cells can survive the fabrication and storage stages with the incorporation of cryoprotectant.
• The branched and grid internal channels can provide cells with nutrients and oxygen.
• The hybrid hierarchical construct can be used as a vascular system regeneration template.

The creation of branched vascular systems has attracted significant attention from both scientific and clinical areas. However, it is still a formidable challenge to build a three-dimensional (3-D) branched vascular system mimicking the native vascular systems with the traditional or existing fabrication methods. Here we demonstrate rapid manufacturing of a hybrid hierarchical polyurethane-cell/Hydrogel construct by a double-nozzle low-temperature deposition system. Based on this approach, a 3-D vascular template with both synthetic scaffold polymer and cell/hydrogel systems was constructed. The synthetic PU was used as an external scaffold material to provide mechanical support, while the gelatin/alginate/fibrinogen hydrogel was used as an internal scaffold material for adipose-derived stem cell (ADSC) accommodation. After the fabrication stages, the coherent 3-D composite construct was thawed at room temperature, crosslinked/polymerized with aqueous solutions, cultured in vitro under static or dynamic conditions, and embedded in vivo with stable architectures and excellent biocompatibilities. This technology will enable rapid manufacture of complex branched vascular templates for a wide array of scientific and clinical applications.