Recent research progresses of bioengineered biliary stents

Abstract

Bile duct lesion, including benign (eg. occlusion, cholelithiasis, dilatation, malformation) and malignant (cholangiocarcinoma) diseases, is a frequently encountered challenge in hepatobiliary diseases, which can be repaired by interventional or surgical procedures. A viable cure for bile duct lesions is implantation with biliary stents. Despite the placement achieved by current clinical biliary stents, the creation of functional and readily transplantable biliary stents remains a formidable obstacle. Excellent biocompatibility, stable mechanics, and absorbability are just a few benefits of using bioengineered biliary stents, which can also support and repair damaged bile ducts that drain bile. Additionally, cell sources & organoids derived from the biliary system that are loaded onto scaffolds can encourage bile duct regeneration. Therefore, the implantation of bioengineered biliary stent is considered as an ideal treatment for bile duct lesion, holding a broad potential for clinical applications in future. In this review, we look back on the development of conventional biliary stents, biodegradable biliary stents, and bioengineered biliary stents, highlighting the crucial elements of bioengineered biliary stents in promoting bile duct regeneration. After providing an overview of the various types of cell sources & organoids and fabrication methods utilized for the bioengineering process, we present the in vitro and in vivo applications of bioengineered biliary ducts, along with the latest advances in this exciting field. Finally, we also emphasize the ongoing challenges and future development of bioengineered biliary stents.

Keywords: 3D bio-printing; Biliary cell sources; Biodegradable stents; Bioengineering materials; Stent fabrication.

Graphical abstract

Fig. 1

Cell sources & organoids, fabrication methods and applications of bioengineered biliary stents. Created with BioRender.com. iPSCs, Induced Pluripotent Stem Cells.

Fig. 2

Biliary stents with different materials, shapes, biodegradability and functions. (A) A 10 mm diameter Fully Covered Self-Expandable Metal Stent corresponds to seven 10 Fr plastic stents [32]. Copyright © 2019, Andrea Tringali et al. (B) A biodegradable biliary stent with the helicoidal shape that allows for bile flow from the inside channel and along the outer stent surface [49]. Copyright © 2020 by the American Society for Gastrointestinal Endoscopy. (C) The biodegradation time of biodegradable polymer biliary stents and conventional biliary stents [50]. Copyright © 2020 Japan Gastroenterological Endoscopy Society. (D) A tri-layered film for biliary stents with antibiotic coatings and antitumour coatings [51]. Copyright © 2021 Elsevier B.V. (E) A polymer biodegradable biliary stent with nanoengineered surfaces that prevents hyperplasia and bacterial responses [52]. Copyright © 2024, KeAi Communications Co. Ltd.

Fig. 3

Bioengineering materials. (A) Decellularization in liver and construction of functional ductal organoids [65]. Copyright © 2023, KeAi Communications Co. Ltd. (B) The swelling behaviour of hydrogel stent [74]. Reproduced from Ref. 47 with permission from the Royal Society of Chemistry. (C) A synthesized norbornene-functionalized neutral soluble collagen (NorCol) enabled for temperature-based, ion-based, and photo-based bio-printing [90]. Copyright © 2021, American Chemical Society.

Fig. 4

Fabrication processes of tissue engineering tubular scaffolds. (A) Scheme of PMSC collagen seeded stent [130]. Copyright © 2019 Licensee MDPI. (B) Scheme of induced-MSC-laden dual-layer tubular scaffold [91]. Copyright © 2021 Elsevier Ltd. (C) Automated fabrication strategy of patterned tubular architectures [134]. Copyright © 2015 IOP Publishing Ltd. (D) Fabrication strategy of dip coating through 3D printed template [135]. Copyright © 2017 American Chemical Society. (E) Scheme of DLP stereolithography-based biliary stent [136]. Copyright © 2021 Elsa Mazari-Arrighi et al. Published by Elsevier Ltd. (F) Scheme of the 4D biofabrication of self-folding hydrogel-based (cell-laden) tubes [137]. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fig. 5

Implantation techniques of bioengineered biliary stents. (A) Anastomosis of CBD and the descending duodenumat with a biliary stent [162]. Copyright © 2005 American Society of Transplantation & American Society of Transplant Surgeons. (B) Anastomosis of biliary stent and CBD via laparotomy [91]. Copyright © 2021 Elsevier Ltd. (C) The procedure of bioengineered biliary stent implanting under light microscopy [135]. Copyright © 2017 American Chemistry Society. (D) Process for placing an advanced stent into the rabbit common bile duct through a modified central venous catheterization. Ⅰ, the guide wire and plastic jacket tube inserted into CBD; Ⅱ, the stent sutured to the inner wall of CBD [165]. Copyright © 2013, Spandidos Publications. (E) The procedure of bioengineered biliary stent implanting and releasing via balloon catheter under fluoroscopy [52]. Copyright © 2024, KeAi Communications Co. Ltd.