Progress and Current Limitations of Materials for Artificial Bile Duct Engineering

Abstract

Bile duct injury (BDI) and bile tract diseases are regarded as prominent challenges in hepatobiliary surgery due to the risk of severe complications. Hepatobiliary, pancreatic, and gastrointestinal surgery can inadvertently cause iatrogenic BDI. The commonly utilized clinical treatment of BDI is biliary-enteric anastomosis. However, removal of the Oddi sphincter, which serves as a valve control over the unidirectional flow of bile to the intestine, can result in complications such as reflux cholangitis, restenosis of the bile duct, and cholangiocarcinoma. Tissue engineering and biomaterials offer alternative approaches for BDI treatment. Reconstruction of mechanically functional and biomimetic structures to replace bile ducts aims to promote the ingrowth of bile duct cells and realize tissue regeneration of bile ducts. Current research on artificial bile ducts has remained within preclinical animal model experiments. As more research shows artificial bile duct replacements achieving effective mechanical and functional prevention of biliary peritonitis caused by bile leakage or obstructive jaundice after bile duct reconstruction, clinical translation of tissue-engineered bile ducts has become a theoretical possibility. This literature review provides a comprehensive collection of published works in relation to three tissue engineering approaches for biomimetic bile duct construction: mechanical support from scaffold materials, cell seeding methods, and the incorporation of biologically active factors to identify the advancements and current limitations of materials and methods for the development of effective artificial bile ducts that promote tissue regeneration.

Cellular Homeostasis and Repair in the Biliary Tree

“…Finally, inadequate vascularization is still the main obstacle to the long-term survival of bioengineered bile ducts. 152,153 If these limitations can be overcome, the clinical translation of bioengineered bile ducts will become feasible in the future.…”

Angiogenic Modification of Microfibrous Polycaprolactone by pCMV-VEGF165 Plasmid Promotes Local Vascular Growth after Implantation in Rats

“…The timing of stimulation of vascular growth is crucial for successful outcomes after graft implantation. Stimulation of angiogenesis has been shown to be especially important in the early period after scaffold implantation [ 13 , 14 , 15 , 16 ]. Previously, it was shown that the use of protein growth factors (fibroblast growth factors, epidermal growth factor, vascular endothelial growth factor (VEGF), platelet-derived growth factor, and other pro-angiogenic biomolecules) and gene therapy drugs, when applied locally, deposited on the surface of the material or embedded in the volume, promoted vascular growth in an implant [ 17 , 18 , 19 ].…”

Biomechanical Behaviors and Degradation Properties of Multilayered Polymer Scaffolds: The Phase Space Method for Bile Duct Design and Bioengineering

“…Recovery of bile flow in the case of bile duct damage and biliodigestive anastomosis stricture still remains among the key challenges in modern medicine [ 1 , 2 , 3 ]. The use of balloon dilatation and plastic stent installation is not efficient enough because of their frequent migration from the bile duct lumen, the need for re-intervention every three months due to stent lumen obturation by the bile salts, and potential complications that may occur during their repeated placement [ 4 , 5 ].…”

“…The interest in the use of biocompatible and biodegradable materials for biliary stent construction is motivated by their degradability in natural conditions and incorporation into the lumen wall. Hence, biocompatible and biodegradable materials can be used for the formation of tissue-engineered grafts that may represent an alternative to stents and help to avoid the risk of stent migration [ 3 , 6 , 7 ].…”