Hamada Takashi, Nakamura Anna, Soyama Akihiko, Sakai Yusuke, Miyoshi Takayuki, Yamaguchi Shun, Hidaka Masaaki, Hara Takanobu, Kugiyama Tota, Takatsuki Mitsuhisa, Kamiya Akihide, Nakayama Koichi, Eguchi Susumu
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Department of Regenerative Medicine and Biomedical Engineering, Faculty of Medicine, Saga University, Japan.
Regen Ther. 2021 Feb 24;16:81-89. doi: 10.1016/j.reth.2021.02.001. eCollection 2021 Mar.
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.
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.
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.
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.
胆管损伤或胆管对胆管胆肠吻合术后的胆管狭窄是严重并发症,由于需要定期更换支架,会显著降低患者的生活质量。本研究旨在构建一种无支架管状结构作为植入移植物来治疗胆管并发症。
使用生物3D打印机制作同种异体猪成纤维细胞的无支架管状结构,即成纤维细胞管,并将其作为胆管对胆管胆肠吻合术的植入移植物植入猪体内。
尽管成纤维细胞管比天然胆管更脆弱,但仍足够坚固以进行缝合。在实验期间,猪的血清肝胆酶水平保持稳定。微型计算机断层扫描显示无胆管狭窄、无胆漏、无肝内胆管扩张。所有切除标本中均保留了管状结构,且成纤维细胞在移植物部位持续存在。免疫组织化学分析显示成纤维细胞管中有血管生成,且胆管上皮未延伸至成纤维细胞管腔内。
本研究结果表明,使用新型生物3D打印机由猪成纤维细胞构建的无支架管状结构成功重建了肝外胆管。这种结构可为肝胆疾病患者提供一种新型的再生治疗方法。