Converging 3D Printing and Electrospinning: Effect of Poly(l‐lactide)/Gelatin Based Short Nanofibers Aerogels on Tracheal Regeneration

Recently, various tissue engineering based strategies have been pursued for the regeneration of tracheal tissues. However, previously developed tracheal scaffolds do not accurately mimic the microstructure and mechanical behavior of the native trachea, which restrict their clinical translation. Here, tracheal scaffolds are fabricated by using 3D printing and short nanofibers (SF) dispersion of poly(l-lactide)/gelatin (0.5-1.5 wt%) to afford tracheal constructs. The results display that the scaffolds containing 1.0 wt % of SF exhibit low density, good water absorption capacity, reasonable degradation rate, and stable mechanical properties, which were comparable to the native trachea. Moreover, the designed scaffolds possess good biocompatibility and promote the growth and infiltration of chondrocytes in vitro. The biocompatibility of tracheal scaffolds is further assessed after subcutaneous implantation in mice for up to 4 and 8 weeks. Histological assessment of tracheal constructs explanted at week 4 shows that scaffolds can maintain their structural integrity and support the formation of neo-vessels. Furthermore, cell-scaffold constructs gradually form cartilage-like tissues, which mature with time. Collectively, these engineered tracheal scaffolds not only possess appropriate mechanical properties to afford a stabilized structure but also a biomimetic extracellular matrix-like structure to accomplish tissue regeneration, which may have broad implications for tracheal regeneration.