Fabrication of Stand-Alone Cell-Laden Collagen Vascular Network Scaffolds Using Fugitive Pattern-Based Printing-Then-Casting Approach

Vascular networks are of great significance in tissue engineering and viewed as the first step to fabricate human tissues. Although various techniques have been investigated to create vascular and vascular-like networks, the fabrication of stand-alone pure collagen-based vascular constructs is still a challenge because of the poor extrudability, weak mechanical property, and long cross-linking time of pure collagen solutions. In this study, a fugitive pattern-based printing-then-casting approach is investigated. The proposed alginate-based fugitive ink has excellent mechanical strength (by adding Laponite nanoclay), printability (by adding Laponite nanoclay), and controllable gelation rate (by adding disodium hydrogen phosphate). Using this fugitive ink, complex vascular-like structures can be easily printed and cross-linked in Laponite EP bath as fugitive vascular tree patterns. Each fugitive vascular tree pattern is then embedded in a gelatin bath to make a gelatin mold with the tree patterns. With the help of sodium citrate, the fugitive vascular tree pattern is liquefied and removed to create the gelatin mold with vascular channels. Finally, a stand-alone collagen vascular network scaffold embedded with fibroblasts can be fabricated by casting the cell-laden collagen suspension into the gelatin mold and releasing it from the mold at 37 °C. The cell-related investigations indicate that the cells grow and spread well in the pure collagen vascular network scaffold. The proposed hybrid printing-then-casting approach also provides a feasible technology to fabricate with materials having low viscosity, long gelation time, and poor mechanical property.