4-Axis printing microfibrous tubular scaffold and tracheal cartilage application

Long-segment defects remain a major problem in clinical treatment of tubular tissue reconstruction. The design of tubular scaffold with desired structure and functional properties suitable for tubular tissue regeneration remains a great challenge in regenerative medicine. Here, we present a reliable method to rapidly fabricate tissue- engineered tubular scaffold with hierarchical structure via 4-axis printing system. The fabrication process can be adapted to various biomaterials including hydrogels, thermoplastic materials and thermosetting materials. Using polycaprolactone (PCL) as an example, we successfully fabricated the scaffolds with tunable tubular architecture, controllable mesh structure, radial elasticity, good flexibility, and luminal patency. As a preliminary demonstration of the applications of this technology, we prepared a hybrid tubular scaffold via the combination of the 4-axis printed elastic poly(glycerol sebacate) (PGS) bio-spring and electrospun gelatin nanofibers. The scaffolds seeded with chondrocytes formed tubular mature cartilage-like tissue both via in vitro culture and subcutaneous implantation in the nude mouse, which showed great potential for tracheal cartilage reconstruction.