Skip to main content

Advertisement

Log in

Regeneration of extrahepatic bile ducts by tissue engineering with a bioabsorbable polymer

  • Minireview
  • Published:
Journal of Artificial Organs Aims and scope Submit manuscript

Abstract

With the widespread adoption of laparoscopic cholecystectomy and living-donor liver transplantation in recent years, complications involving the biliary system, stenosis in particular, are increasing. Various invasive and non-invasive techniques are now available for the treatment of biliary stenosis, but all are compromised by a high risk of recurrence and other problems. As a potential solution, our group has developed a bioabsorbable polymer (BAP) tube for implantation as a bypass graft. In the study reported here, we implanted this BAP tube and confirmed bile duct regeneration at the graft site after the tube had been degraded and absorbed into the body. We briefly describe our findings on extrahepatic biliary tissue regeneration, focusing on the possibility of its clinical application. This artificial bile duct may promote the development of novel treatments for biliary disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ammori BJ, Joseph S, Attia M, Lodge JP. Biliary strictures complicating pancreaticoduodenectomy. Int J Pancreatol. 2000;28:15.

    Article  PubMed  CAS  Google Scholar 

  2. Egawa H, Inomata Y, Uemoto S, Asonuma K, Kiuchi T, Fujita S, Hayashi M, Matamoros MA, Itou K, Tanaka K. Biliary anastomotic complications in 400 living related liver transplantations. World J Surg. 2001;25:1300.

    Article  PubMed  CAS  Google Scholar 

  3. Wojcicki M, Milkiewicz P, Silva M. Biliary tract complications after liver transplantation: a review. Dig Surg. 2008;25:245–57.

    Article  PubMed  Google Scholar 

  4. Maheshwari A, Maley W, Li Z, Thuluvath PJ. Biliary complications and outcomes of liver transplantation from donors after cardiac death. Liver Transpl. 2007;13:1645–53.

    Article  PubMed  Google Scholar 

  5. Nishida S, Nakamura N, Kadono J, Komokata T, Sakata R, Madariaga JR, Tzakis AG. Intrahepatic biliary strictures after liver transplantation. J Hepatobiliary Pancreat Surg. 2006;13:511–6.

    Article  PubMed  Google Scholar 

  6. Sugawara Y, Makuuchi M, Takayama T, Imamura H, Dowaki S, Mizuta K, Kawarasaki H, Hashizume K. Small-for-size grafts in living-related liver transplantation. J Am Coll Surg. 2001;192:510.

    Article  PubMed  CAS  Google Scholar 

  7. Halme L, Hockerstedt K, Lautenschlager I. Cytomegalovirus infection and development of biliary complications after liver transplantation. Transplantation. 2003;75:1853.

    Article  PubMed  Google Scholar 

  8. Miyazawa M, Torii T, Toshimitsu Y, Okada K, Koyama I, Ikada Y. A tissue-engineered artificial bile duct grown to resemble the native bile duct. Am J Transplant. 2005;5:1541–7.

    Article  PubMed  Google Scholar 

  9. Shimono K, Nose Y. The need to develop artificial bile ducts. Artif Organs. 1995;19:115.

    Article  PubMed  CAS  Google Scholar 

  10. Xu J, Sun S, Zhang Q, Chen J, Wu L, Liu W, Guo G. Experiment for a polyurethane replacement of the common bile duct. Chin Med J (Engl). 1998;111:86.

    CAS  Google Scholar 

  11. Rosen M, Ponsky J, Petras R, Fanning A, Brody F, Duperier F. Small intestinal submucosa as a bioscaffold for biliary tract regeneration. Surgery. 2002;132:480.

    Article  PubMed  Google Scholar 

  12. Teebken OE, Haverich A. Tissue engineering of small diameter vascular grafts. Eur J Vasc Endovasc Surg. 2002;23:475.

    Article  PubMed  Google Scholar 

  13. Shin’oka T, Imai Y, Ikada Y. Transplantation of a tissue-engineered pulmonary artery. N Engl J Med. 2001;344:532.

    Article  PubMed  Google Scholar 

  14. Kaihara S, Kim S, Benvenuto M, Kim BS, Mooney DJ, Tanaka K, Vacanti JP. End-to-end anastomosis between tissue-engineered intestine and native small bowel. Tissue Eng. 1999;5:339.

    Article  PubMed  CAS  Google Scholar 

  15. Perez A, Grikscheit TC, Blumberg RS, Ashley SW, Vacanti JP. Tissue-engineered small intestine: ontogeny of the immune system. Transplantation. 2002;74:619.

    Article  PubMed  CAS  Google Scholar 

  16. Ishizaki Y, Bandai Y, Shimomura K, Idezuki Y, Makuuchi M. Healing process of sutureless choledochojejunostomy in an experimental model. Br J Surg. 1995;82:1118–21.

    Article  PubMed  CAS  Google Scholar 

  17. Watanabe M, Shin’oka T, Tohyama S, Hibino N, Konuma T, Matsumura G, Kosaka Y, Ishida T, Imai Y, Yamakawa M, Ikada Y, Morita S. Tissue-engineered vascular autograft: inferior vena cava replacement in a dog model. Tissue Eng. 2001;7:429–39.

    Article  PubMed  CAS  Google Scholar 

  18. Noishiki Y, Tomizawa Y, Yamane Y, Matsumoto A. Autocrine angiogenic vascular prosthesis with bone marrow transplantation. Nat Med. 1996;2:90–3.

    Article  PubMed  CAS  Google Scholar 

  19. Bhattacharya V, McSweeney PA, Shi Q, Bruno B, Ishida A, Nash R, Storb RF, Sauvage LR, Hammond WP, Wu MH. Enhanced endothelialization and microvessel formation in polyester grafts seeded with CD34(+) bone marrow cells. Blood. 2000;95:581–5.

    PubMed  CAS  Google Scholar 

  20. Dalakas E, Newsome PN, Boyle S, Brown R, Pryde A, McCall S, Hayes PC, Bickmore WA, Harrison DJ, Plevris JN. Bone marrow stem cells contribute to alcohol liver fibrosis in humans. Stem Cells Dev. 2010;19:1417–25.

    Article  PubMed  CAS  Google Scholar 

  21. Jang YY, Collector MI, Baylin SB, Diehl AM, Sharkis SJ. Hematopoietic stem cells convert into liver cells within days without fusion. Nat Cell Biol. 2004;6:532–9.

    Google Scholar 

  22. Oh SH, Witek RP, Bae SH, Zheng D, Jung Y, Piscaglia AC, Petersen BE. Bone marrow-derived hepatic oval cells differentiate into hepatocytes in 2-acetylaminofluorene/partial hepatectomy-induced liver regeneration. Gastroenterology. 2007;132:1077–87.

    Article  PubMed  CAS  Google Scholar 

  23. Tabibian JH, Asham EH, Han S, Saab S, Tong MJ, Goldstein L, Busuttil RW, Durazo FA. Endoscopic treatment of postorthotopic liver transplantation anastomotic biliary strictures with maximal stent therapy (with video). Gastrointest Endosc. 2010;71:505–12.

    Article  PubMed  Google Scholar 

  24. Pottakkat B, Vijayahari R, Prakash A, Singh RK, Behari A, Kumar A, Kapoor VK, Saxena R. Factors predicting failure following high bilio-enteric anastomosis for post-cholecystectomy benign biliary strictures. J Gastrointest Surg. 2010;14:1389–94.

    Article  PubMed  Google Scholar 

  25. Cantwell CP, Pena CS, Gervais DA, Hahn PF, Dawson SL, Mueller PR. Thirty years’ experience with balloon dilation of benign postoperative biliary strictures: long-term outcomes. Radiology. 2008;249:1050–7.

    Article  PubMed  Google Scholar 

  26. Sikora SS, Srikanth G, Agrawal V, Gupta RK, Kumar A, Saxena R, Kapoor VK. Liver histology in benign biliary stricture: fibrosis to cirrhosis… and reversal? J Gastroenterol Hepatol. 2008;23:1879–84.

    Article  PubMed  Google Scholar 

  27. Corvera CU, Blumgart LH, Darvishian F, Klimstra DS, DeMatteo R, Fong Y, D’Angelica M, Jarnagin WR. Clinical and pathologic features of proximal biliary strictures masquerading as hilar cholangiocarcinoma. J Am Coll Surg. 2005;201:862–9.

    Article  PubMed  Google Scholar 

  28. Lillemoe KD, Melton GB, Cameron JL, Pitt HA, Campbell KA, Talamini MA, Sauter PA, Coleman J, Yeo CJ. Postoperative bile duct strictures: management and outcome in the 1990 s. Ann Surg. 2000;232:430–41.

    Article  PubMed  CAS  Google Scholar 

  29. Shah SA, Grant DR, McGilvray ID, Greig PD, Selzner M, Lilly LB, Girgrah N, Levy GA, Cattral MS. Biliary strictures in 130 consecutive right lobe living donor liver transplant recipients: results of a Western center. Am J Transplant. 2007;7:161–7.

    Article  PubMed  CAS  Google Scholar 

  30. Judah JR, Draganov PV. Endoscopic therapy of benign biliary strictures. World J Gastroenterol. 2007;13:3531–9.

    PubMed  Google Scholar 

  31. Lillemoe KD, Pitt HA, Cameron JL. Current management of benign bile duct strictures. Adv Surg. 1992;25:119–74.

    PubMed  CAS  Google Scholar 

  32. Aikawa M, Miyazawa M, Okamoto K, Toshimitsu Y, Torii T, Okada K, Akimoto N, Ohtani Y, Koyama I, Yoshito I. A novel treatment for bile duct injury with a tissue-engineered bioabsorbable polymer patch. Surgery. 2010;147:575–80.

    Article  PubMed  Google Scholar 

  33. Tocchi A, Mazzoni G, Liotta G, Lepre L, Cassini D, Miccini M. Late development of bile duct cancer in patients who had biliary-enteric drainage for benign disease: a follow-up study of more than 1, 000 patients. Ann Surg. 2001;234:210–4.

    Article  PubMed  CAS  Google Scholar 

  34. Bettschart V, Clayton RA, Parks RW, Garden OJ, Bellamy CO. Cholangiocarcinoma arising after biliary-enteric drainage procedures for benign disease. Gut. 2002;51:128–9.

    Article  PubMed  CAS  Google Scholar 

  35. Herba MJ, Casola G, Bret PM, Lough J, Hampson LG. Cholangiocarcinoma as a late complication of choledochoenteric anastomoses. AJR Am J Roentgenol. 1986;147:513–5.

    PubMed  CAS  Google Scholar 

  36. Gouma DJ, Konsten J, Soeters PB, Von Meyenfeldt M, Obertop H. Long-term follow-up after choledochojejunostomy for bile duct stones with complex clearance of the bile duct. Br J Surg. 1989;76:451–3.

    Article  PubMed  CAS  Google Scholar 

  37. Maeda A, Yokoi S, Kunou T, Saeki S, Niinomi N, Uesaka K. Bile duct cancer developing 21 years after choledochoduodenostomy. Dig Surg. 2003;20:331–4.

    Article  PubMed  Google Scholar 

  38. Aikawa M, Miyazawa M, Okada K, Toshimitsu Y, Okamoto K, Akimoto N, Koyama I, Ikada Y. Development of a novel reflux-free bilioenteric anastomosis procedure by using a bioabsorbable polymer tube. J Hepatobiliary Pancreat Sci. 2010;17:284–90.

    Article  PubMed  Google Scholar 

  39. Sakai Y, Tsuyuguchi T, Ishihara T, Yukisawa S, Sugiyama H, Miyakawa K, Kuroda Y, Yamaguchi T, Ozawa S, Yokosuka O. Long-term prognosis of patients with endoscopically treated postoperative bile duct stricture and bile duct stricture due to chronic pancreatitis. J Gastroenterol Hepatol. 2009;24:1191–7.

    Article  PubMed  Google Scholar 

  40. Roumilhac D, Poyet G, Sergent G, Declerck N, Karoui M, Mathurin P, Ernst O, Paris JC, Gambiez L, Pruvot FR. Long-term results of percutaneous management for anastomotic biliary stricture after orthotopic liver transplantation. Liver Transpl. 2003;9:394–400.

    Article  PubMed  Google Scholar 

  41. Miyazawa M, Aikawa M, Okada K, Torii T, Otani Y, Koyama I. Development of bioabsorbable biliary tract stens for treatment of benign biliary stenosis. Jpn J Gastroenterol Surg. 2007;40:1548.

    Google Scholar 

  42. Kasuya K, Shimazu M, Abe Y, Kikuchi S, Itoi T, Ikada Y, Aoki T, Tsuchida A. A newly developed degradable stent for pancreaticojejunostomy after pancreatoduodenectomy. Int Surg. 2010;95:247–56.

    PubMed  Google Scholar 

  43. Bandura WP, Arbulu A. Experimental replacement of the common bile duct with teflon graft. Am Surg. 1961;27:518–24.

    PubMed  CAS  Google Scholar 

  44. Gomez NA, Alvarez LR, Mite A, Andrade JP, Alvarez JR, Vargas PE, Tomala NE, Vivas AF, Zapatier JA. Repair of bile duct injuries with Gore-Tex vascular grafts: experimental study in dogs. J Gastrointest Surg. 2002;6:116–20.

    Article  PubMed  Google Scholar 

  45. Christensen M, Laursen HB, Rokkjaer M, Jensen PF, Yasuda Y, Mortensen FV. Reconstruction of the common bile duct by a vascular prosthetic graft: an experimental study in pigs. J Hepatobiliary Pancreat Surg. 2005;12:231–4.

    Article  PubMed  Google Scholar 

  46. Mendelowitz DS, Beal JM. Expanded polytetrafluoroethylene in reconstruction of the canine biliary system. Am J Surg. 1982;143:221–4.

    Article  PubMed  CAS  Google Scholar 

  47. Bottger T, Mann B, Pickel B, Weber W, Sorger K, Junginger T. Animal experiment studies of pedicled small intestine transplantation as partial extrahepatic bile duct replacement. Langenbecks Arch Chir. 1991;376:77–84.

    Article  PubMed  CAS  Google Scholar 

  48. Belzer FO, Watts JM, Ross HB, Dunphy JE. Auto-reconstruction of the common bile duct after venous patch graft. Ann Surg. 1965;162:346–55.

    Article  PubMed  CAS  Google Scholar 

  49. Aydin M, Bakir B, Kosem M, Kisli E, Genccelep M. Biliary tract reconstruction with autologous rectus sheath graft—an experimental study. Hepatogastroenterology. 2005;52:1019–22.

    PubMed  Google Scholar 

  50. Sedgwick CE. Reconstruction of the common bile duct with a free ureteral graft; an experimental study. Surg Gynecol Obstet. 1951;92:571–3.

    PubMed  CAS  Google Scholar 

  51. Gomez NA, Zapatier JA, Vargas PE. Re: “Small intestinal submucosa as a bioscaffold for biliary tract regeneration”. Surgery. 2004;135:460.

    Article  PubMed  Google Scholar 

  52. El-Assmy A, Hafez AT, El-Sherbiny MT, El-Hamid MA, Mohsen T, Nour EM, Bazeed M. Use of single layer small intestinal submucosa for long segment ureteral replacement: a pilot study. J Urol. 2004;171:1939–42.

    Article  PubMed  Google Scholar 

  53. Paradis K, Langford G, Long Z, Heneine W, Sandstrom P, Switzer WM, Chapman LE, Lockey C, Onions D, Otto E. Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group. Science. 1999;285:1236–41.

    Article  PubMed  CAS  Google Scholar 

  54. Fishman JA, Patience C. Xenotransplantation: infectious risk revisited. Am J Transplant. 2004;4:1383–90.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Mitsuo Miyazawa or Masayasu Aikawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miyazawa, M., Aikawa, M., Okada, K. et al. Regeneration of extrahepatic bile ducts by tissue engineering with a bioabsorbable polymer. J Artif Organs 15, 26–31 (2012). https://doi.org/10.1007/s10047-011-0590-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10047-011-0590-8

Keywords

Navigation