materials Review Progress and Current Limitations of Materials for Artiﬁcial Bile Duct Engineering Qiqi Sun 1,† , Zefeng Shen 2,† , Xiao Liang 2 , Yingxu He 3 , Deling Kong 1 , Adam C. Midgley 1, * and Kai Wang 1, *   Citation: Sun, Q.; Shen, Z.; Liang, X.; He, Y.; Kong, D.; Midgley, A.C.; Wang, K. Progress and Current Limitations of Materials for Artiﬁcial Bile Duct Engineering. Materials 2021, 14, 7468. https://doi.org/10.3390/ma14237468 Academic Editors: Parvez Alam and Alessandro Pegoretti Received: 30 August 2021 Accepted: 25 October 2021 Published: 6 December 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional afﬁl- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China; sunqiqi971018@163.com (Q.S.); kongdeling@nankai.edu.cn (D.K.) 2 Department of General Surgery, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; srrshszf@zju.edu.cn (Z.S.); srrshlx@zju.edu.cn (X.L.) 3 School of Computing, National University of Singapore, Singapore 119077, Singapore; yingxu.he1998@gmail.com * Correspondence: midgleyac@nankai.edu.cn (A.C.M.); 013053@nankai.edu.cn (K.W.) † Authors contributed equally to this work. 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 gastroin- testinal 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 bio- materials 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 con- struction: 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. Keywords: artiﬁcial bile duct; tissue engineering; biomimetic materials; tissue regeneration 1. Introduction Bile duct injury (BDI) is regarded as a substantial clinical challenge in hepatobiliary surgery due to its serious complications [1]. Dependent on the cause of injury, BDI can be divided into iatrogenic BDI (approximately 90–95% of cases) or traumatic BDI [2]. Hepatobiliary, pancreatic surgery, and gastrointestinal surgery can result in iatrogenic BDI, wherein the damage caused by cholecystectomy accounts for approximately 80% of all iatrogenic BDI incidence. Laparoscopic cholecystectomy is the leading choice for cholecystectomy due to the low occurrence of postoperative complications. However, a retrospective study involving 10,123 patients highlighted that laparoscopic cholecystec- tomy may not signiﬁcantly reduce the incidence of iatrogenic BDI, compared to open cholecystectomy. Only a third of iatrogenic BDI are identiﬁable during open surgery and thus receive timely, effective repair and reconstruction [3]. The majority of iatrogenic BDI are diagnosable by insensitive methods such as clinical manifestation, laboratory-based testing, and invasive imaging examination [4]. Stenosis after BDI is associated with the excessive proliferation of ﬁbroblasts, collagen deposition, Materials 2021, 14, 7468. https://doi.org/10.3390/ma14237468 https://www.mdpi.com/journal/materials