Abstract:

Human esophagus is a multi-layered, tubular and hollow organ. Esophagus-related diseases (e.g., Barrett’s esophagus and esophagus cancer) lower the quality of life and threaten millions of lives around the world. Esophagectomy is the most widely used treatment for patients who have esophageal cancer and other esophageal disorders (esophageal atresia, esophageal stricture, megaesophagus, esophageal perforation, esophageal caustic injury, etc.). However, existing solutions including esophagectomy for treating esophagus problems, which involve autografts and/or synthetic prostheses, have limitations in avoiding serious complications and substantial mortality after surgery, facing donor shortage and foreign host response, etc. Tissue engineering (TE) has now shown the promise of providing effective alternatives for esophageal repair. However, many technical challenges exist in esophagus tissue engineering (E-TE) as it is difficult to regenerate multi-strata and evenly stratified esophageal tissue in vitro due to its complex architecture and dynamic mechanical behavior. Animal-derived decellularized scaffolds, electrospun scaffolds, etc. that are reported in previous studies have not advanced E-TE significantly. 3D printing and bioprinting together with new biomaterials (and hence new inks/bioinks) appear highly promising for fabricating structurally complicated and functionally matching scaffolds and cell-scaffold constructs for esophageal repair or augmentation. Conventional hydrogels and composite hydrogels used in E-TE, including poly(vinyl alcohol) (PVA) and gelatin methacryloyl (GelMA), do not provide satisfactory biomechanical properties as a result of the inherent dissonance between stiffness and toughness. A suitably designed and formed cross-linked network inside composite hydrogels that integrates H-bonding, covalent bonding, and crystallization domains will endow the hydrogels with desirable biomechanical properties for E-TE. Also, the introduction of a suitable support bath can facilitate higher-resolution 3D printing of hydrogel TE scaffolds. In this seminar, I shall provide a review of esophagus tissue engineering and introduce 3D printing and bioprinting in E-TE. I shall also highlight our approach and tactics for solving several technical difficulties of 3D printing and bioprinting in E-TE. I shall show our initial results of developing novel photocrosslinkable hydrogels for 3D printing/bioprinting of E-TE scaffolds with desirable and tunable biomechanical properties (tensile strength: 5-25 MPa; strain: 500-2,000%), as well as high-resolution printing of 3D design models for E-TE.

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