Bile duct reconstruction using scaffold-free tubular constructs created by Bio-3D printer

Takashi Hamada; Anna Nakamura; Akihiko Soyama; Yusuke Sakai; Takayuki Miyoshi; Shun Yamaguchi; Masaaki Hidaka; Takanobu Hara; Tota Kugiyama; Mitsuhisa Takatsuki; Akihide Kamiya; Koichi Nakayama; Susumu Eguchi

doi:10.1016/j.reth.2021.02.001

Bile duct reconstruction using scaffold-free tubular constructs created by Bio-3D printer

Regen Ther. 2021 Feb 24:16:81-89. doi: 10.1016/j.reth.2021.02.001. eCollection 2021 Mar.

Authors

Affiliations

¹ Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
² Department of Regenerative Medicine and Biomedical Engineering, Faculty of Medicine, Saga University, Japan.
³ Department of Chemical Engineering, Faculty of Engineering, Graduate School, Kyushu University, Japan.
⁴ Department of Molecular Life Sciences, Tokai University School of Medicine, Japan.

Abstract

Introduction: Biliary strictures after bile duct injury or duct-to-duct biliary reconstruction are serious complications that markedly reduce patients' quality of life because their treatment involves periodic stent replacements. This study aimed to create a scaffold-free tubular construct as an interposition graft to treat biliary complications.

Methods: Scaffold-free tubular constructs of allogeneic pig fibroblasts, that is, fibroblast tubes, were created using a Bio-3D Printer and implanted into pigs as interposition grafts for duct-to-duct biliary reconstruction.

Results: Although the fibroblast tube was weaker than the native bile duct, it was sufficiently strong to enable suturing. The pigs' serum hepatobiliary enzyme levels remained stable during the experimental period. Micro-computed tomography showed no biliary strictures, no biliary leakages, and no intrahepatic bile duct dilations. The tubular structure was retained in all resected specimens, and the fibroblasts persisted at the graft sites. Immunohistochemical analyses revealed angiogenesis in the fibroblast tube and absence of extensions of the biliary epithelium into the fibroblast tube's lumen.

Conclusions: This study's findings demonstrated successful reconstruction of the extrahepatic bile duct with a scaffold-free tubular construct created from pig fibroblasts using a novel Bio-3D Printer. This construct could provide a novel regenerative treatment for patients with hepatobiliary diseases.

Keywords: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Artificial bile duct; Bio-3D printer; Cr, creatinine; DMEM, Dulbecco's Modified Eagle's Medium; EDTA, trypsin-ethylenediaminetetraacetic acid; FBS, fetal bovine serum; IBDI, iatrogenic bile duct injury; KCL, potassium chloride; LDLT, living donor liver transplantation; PBS, phosphate-buffered saline; QOL, quality of life; Reconstruction; Scaffold-free tubular construct; T-Bil, total bilirubin; γ-GTP, γ-glutamyl transpeptidase.