Biomimetic tracheal development with interspersed cartilage and vascularized connective tissue via 3D bio-printing technique for prompt segmental tracheal reconstruction

Segmental tracheal reconstruction remains a significant clinical challenge due to the lack of ideal tracheal substitutes. 3D bio-printing technique offers a promising revenue for the development of native-like tracheal substitutes. However, several challenges remain to be addressed, including deformation of 3D-printed C-shaped cell-laden hydrogels, fusion of regenerated C-shaped cartilage, and difficulty in regenerating vascularized connective tissue. Herein, we utilized 3D printing techniques to fabricate C-shaped chondrocyte-laden GelMA/PCL (CcGP) and S-shaped PCL chains (SPC). These were assembled into the SPC-CcGP construct, followed by mold casting (VEGF@GelMA) to establish tissue-engineered tracheal construct (TETC). In vitro experiments confirmed the stable chondrogenic potential of CcGP and the angiogenic capability of VEGF@GelMA. Subcutaneous in nude mice and orthotopic transplantation in rabbit model further demonstrated that the TETC could achieve stable regeneration of cartilage and vascularized connective tissue. The engineered trachea could maintain luminal patency following promptly repair of rabbit tracheal defects. This study offers a promising approach for developing engineered tracheas with regenerated cartilage and vascularized connective tissue for prompt and effective segmental tracheal defect repair.