Priya Ranganathan, Seung Hoon Han, In Gul Kim, Dageon Oh, Yewon Kim, Kyung-Noh Yoon, Garin Kim, Young Lee, Masoud Shirzad, Gyeongmi Lee, Jungeun Choi, Jin Myoung Yoo, G.H. Lee, Young Jick Kim, Jungirl Seok, Ji Youl Lee, Sang‐Hyug Park, Jung‐Woog Shin, Seung Yun Nam, Eun‐Jae Chung
Esophageal reconstruction faces critical challenges due to limitations in current techniques, including inadequate mechanical properties, poor tissue integration, and insufficient functional regeneration. This study presents a novel biofabrication strategy for developing artificial esophageal scaffolds by integrating electrospinning, embedded digital light processing (DLP), and extrusion-based bioprinting techniques. These scaffolds are composed of flexible electrospun polyurethane (PU) nanofibers wherein silk fibroin methacryloyl (Sil-MA) is embedded within the PU layer to enhance mechanical strength and hydrophilicity. Decellularized esophageal extracellular matrix (EdECM) is deposited onto the scaffolds to promote tissue regeneration. Comprehensive in vitro and in vivo evaluations reveal that the PU/Sil-MA/EdECM scaffolds exhibit superior mechanical properties, enhanced cell adhesion, and significant improvements in smooth muscle and epithelial tissue regeneration. Moreover, in a rat model with partial esophageal defects, the scaffolds demonstrate successful tissue integration, reduced postoperative complications, and restoration of esophageal function, including peristalsis and nerve regeneration. Altogether, this integrated biofabrication approach offers a promising solution for esophageal reconstruction by effectively addressing the current challenges and paving the way for future clinical applications in regenerative medicine. Graphical abstract illustrating the sequential biofabrication of a PU/Sil-MA/EdECM scaffold for esophageal tissue engineering (left), followed by the construction of the full scaffold with a circumferential structure mimicking the native esophagus. The final section (right) depicts the surgical transplantation of the engineered scaffold into an esophageal circumferential defect, highlighting its potential application in esophageal reconstruction.