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Application of hydrogels as submucosal fluid cushions for endoscopic mucosal resection and submucosal dissection

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  • Biomaterials
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Abstract

Numerous new techniques have recently been reported and described for the endoscopic mucosal resection (EMR) of large superficial lesions of the gastrointestinal tract, using various natural, synthetic, and semi-synthetic materials such as chitin/chitosan and their derivatives. Although saline-assisted EMR is an established minimally invasive therapy, en bloc resection and histopathological analyses are required to determine its curative potential. In addition, complete resection of lesions of >2 cm in diameter remains difficult, despite improved EMR techniques. The development of endoscopic submucosal dissection (ESD) has increased dissection rates for en bloc resection of large lesions, but perforation occurs more frequently during ESD than during EMR. Submucosal injections of those biomaterials which have high viscosity and hydrogelatinization ability as submucosal fluid cushions (SFC) may facilitate ESD as well as EMR for the treatment of superficial tumors of the alimentary tract. In this review, we describe the application of biomaterials such as chitosan derivatives, sodium hyaluronate, and 50 % glucose as a SFC for ESD, focusing photocrosslinked chitosan hydrogels (PCH) which we have originally developed.

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References

  1. Nagpal K, Singh SK, Mishra DN. Chiotsan nanoparticles: a promising system in novel drug delivery. Chem Pharm Bull. 2010;58:1423–30.

    Article  CAS  PubMed  Google Scholar 

  2. Xu YM, Du YM. Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles. Int J Pharm. 2003;250:215–26.

    Article  CAS  PubMed  Google Scholar 

  3. Kizilel S, Garfinkel M, Opara E. The bioartificial pancreas: progress and challenges. Diabetes Technol Ther. 2005;7:968–85.

    Article  CAS  PubMed  Google Scholar 

  4. Horio T, Ishihara M, Fujita M, Kishimoto S, Kanatani Y, Ishizuka T, Nogami Y, Nakamura S, Tanaka Y, Maehara T. Hemostatic effects of photocrosslinkable chitosan hydrogel-mixed photocrosslinked chitosan sponges (PCM-S) on hepatic bleeding in rats. Artif Org. 2010;34:342–7.

    Article  CAS  Google Scholar 

  5. Hattori H, Amano Y, Nogami Y, Kawakami M, Yura H, Ishihara M. Development of a novel emergency hemostatic kit for severe hemorrhage. Artif Org. 2013;37:478–81.

    Article  Google Scholar 

  6. Obara K, Ishihara M, Fujita M, Kanatani Y, Hattori H, Matsui T, Takase B, Maehara T. Acceleration of wound healing in healing-impaired db/db mice with photocrosslinkable chitosan hydrogel containing fibroblast growth factor-2. Wound Repair Regen. 2005;13:390–7.

    Article  PubMed  Google Scholar 

  7. Ishihara M, Ono K, Sato M, Nakanishi K, Saito Y, Yura H, Matsui T, Hattori H, Kikuchi M, Kurita A. Acceleration of wound contraction and healing with photocrosslinkable chitosan hydrogel. Wound Rep Regen. 2001;9:513–21.

    Article  CAS  Google Scholar 

  8. Shi C, Zhu Y, Ran Wang M, Yongping S, Cheng T. Therapeutic potential of chitosan and its derivatives in regenerative medicine. J Surg Res. 2006;133:185–92.

    Article  CAS  PubMed  Google Scholar 

  9. Mi FL, Tan YC, Liang HF, Sung HW. In vivo biocompatibility and degradability of a novel injectable-chitosan-based implant. Biomaterials. 2002;23:181–91.

    Article  CAS  PubMed  Google Scholar 

  10. Onuki Y, Bhardwaj U, Papadimitrakopoulos F, Burgess DJ. A review of the biocompatibility of implantable devices: Current challenges to overcome foreign body response. J Diabetes Sci Tech. 2008;2:1003–15.

    Article  Google Scholar 

  11. VandeVord PJ, Matthew HWT, DeSilva SP, Mayton L, Wu B, Wooley PH. Evaluation of the biocompatibility of a chitosan scaffold in mice. J Biomed Mater Res. 2001;59:585–90.

    Article  Google Scholar 

  12. Ishihara M, Fujita M, Kishimoto S, Hattori H, Kanatani Y. Biological, chemical, and physical compatibility of chitosan and biopharmaceuticals. In: Samento B, Neves JD, editors. Chitosan-based systems for biopharmaceuticals. Wiley, West Sussex; 2012. pp 93–107.

  13. No HK, Meyers SP. Chitosan for treatment of wastewaters. Rev Environ Contam Toxicol. 2000;163:1–27.

    CAS  PubMed  Google Scholar 

  14. Ishihara M, Obara K, Nakamura S, Fujita M, Masuoka K, Kanatani Y, Takase B, Hattori H, Morimoto Y, Ishihara M, Maehara T, Kikuchi M. Chitosan hydrogel as a drug delivery carrier to control angiogenesis. J Artif Org. 2006;9:8–16.

    Article  CAS  Google Scholar 

  15. Hirao M, Masuda K, Asanuma T, Naka H, Noda K, Matsuura K, Yamaguchi O, Ueda N. Endoscopic resection of early gastric cancer and other tumors with local injection of hypertonic saline-epinephrine. Gastrointest Endosc. 1988;34:264–9.

    Article  CAS  PubMed  Google Scholar 

  16. Tada M, Inoue H, Yabata E, Okabe S, Endo M. Colonic mucosal resection using a transparent cap-fitted endoscope. Gastroentest Endosc. 1996;44:63–5.

    Article  CAS  Google Scholar 

  17. Inoue H, Kawano T, Tani M, Takeshita K, Iwai T. Endoscopic mucosal resection using a cap: techniques for use and preventing perforation. Can J Gastroenterol. 1999;13:477–80.

    CAS  PubMed  Google Scholar 

  18. Suzuki H. Endoscopic mucosal resection using ligating device for early gastric cancer. Gastrointest Endosc Clin N Am. 2001;11:511–8.

    CAS  PubMed  Google Scholar 

  19. Fujishiro M, Yahagi N, Kashimura K, Matsuura T, Nakamura M, Kakushima N, Kodashima S, Ono S, Kobayashi K, Hashimoto T, Yamamichi N, Takeishi A, Shimozu Y, Oka M, Ichinose M, Omata M. Tissue damage of different submucosal injection solutions for EMR. Gastrointest Endosc. 2005;62:933–42.

    Article  PubMed  Google Scholar 

  20. Feitoza AB, Gostout CJ, Burgart LJ, Burkert A, Herman LJ, Rajan E. Hydroxypropyl methylcellulose: a better submucosal fluid cushion for endoscopic mucosal resection. Gastrointest Endosc. 2003;57:41–7.

    Article  PubMed  Google Scholar 

  21. Yamamoto H, Yube T, Isoda N, Sato Y, Sekine Y, Higashizawa T, Ido K, Kimura K, Kanai N. A novel method of endoscopic mucosal resection using sodium hyaluronate. Gastrointest Endosc. 1999;50:251–6.

    Article  CAS  PubMed  Google Scholar 

  22. Katsinelos P, Kountouras J, Paroutoglou G, Chatzimavroudis G, Zavos C, Pilpilidis I, Gelas G, Paikos D, Karakousis K. A comparative study of 50% dextrose and normal saline solution on their ability to create sbmucosal fluid cushions for endoscopic resection of sessile rectosigmoid polyps. Gastrointest Endosc. 2008;68:692–8.

    Article  PubMed  Google Scholar 

  23. Ono K, Saito Y, Yura H, Ishikawa K, Kurita A, Ishihara M. Photocrosslinkable chitosan as a biological adhesive. J Biomed Mater Res. 2000;49:289–95.

    Article  CAS  PubMed  Google Scholar 

  24. Ono K, Ishihara M, Ozeki Y, Deguchi H, Sato M, Saito Y, Yura H, Sato M, Kikuchi M, Kurita A, Maehara T. Experimental evaluation of photocrosslinkable chitosan as a biological adhesive with surgical application. Surgery. 2001;130:844–50.

    Article  CAS  PubMed  Google Scholar 

  25. Ishizuka T, Hayashi T, Ishihara M, Yoshizumi Y, Aiko S, Nakamura S, Yura H, Kanatani Y, Nogami Y, Maehara T. Submucosal injection, for endoscopic mucosal resection, of photocrosslinkable chitosan hydrogel in DMEM/F12 medium. Endoscopy. 2007;39:428–33.

    Article  CAS  PubMed  Google Scholar 

  26. Hayashi T, Matsuyama T, Hanada K, Nakanishi K, Uenoyama M, Fujita M, Ishihara M, Kikuchi M, Ikeda T, Tajiri H. Usefulness of photocrosslinkable chitosan for endoscopic cancer treatment in alimentary tract. J Biomed Mater Res, Part B. 2004;71B:367–72.

    Article  CAS  Google Scholar 

  27. Ishizuka T, Ishihara M, Aiko S, Nogami Y, Nakamura S, Kanatani Y, Kishimoto S, Hattori H, Horio T, Tanaka Y, Maehara T. Experimental evaluation of photocrosslinkable chitosan hydrogel as injection solution for endoscopic resection. Endoscopy. 2009;41:25–8.

    Article  CAS  PubMed  Google Scholar 

  28. Kumano I, Ishihara M, Nakamura S, Kishimoto S, Fujita M, Hattori H, Horio T, Tanaka Y, Hase K, Maehara T. Endoscopic submucosal dissection for pig esophagus by using photocrosslinkable chitosan hydrogel as submucosal fluid cushion. Gastrointest Endosc. 2012;75:841–88.

    Article  PubMed  Google Scholar 

  29. Otani Y, Tabata Y, Ikada Y. A new biological glue from gelatin and poly (l-glutamic acid). J Biomed Mater Res. 1996;31:158–66.

    Article  CAS  PubMed  Google Scholar 

  30. Tseng YC, Hyon SH, Ikada Y. Modification of synthesis and investigation of properties for 2-cyanoacrylates. Biomaterials. 1990;11:73–9.

    Article  CAS  PubMed  Google Scholar 

  31. Vanholder R, Misotten A, Roels H, Matton G. Cyanoacrylate tissue adhesive for closing skin wounds: a double blind randomized comparison with suture. Biomaterials. 1993;14:737–42.

    Article  CAS  PubMed  Google Scholar 

  32. Pederson TB, Hongel JL, Pilegaard HK, Hasenkam JM. Comparative study of lung sealants in porcine ex vivo model. Ann Thorac Surg. 2012;94:234–40.

    Article  Google Scholar 

  33. Moy OJ, Peimer CA, Koniuchi MP, Hoeard C, Zielezny M, Katikaneni PR. Fibrin seal adhesive versus nonadsorbable microsuture in peripheral nerve repair. J Hand Surg. 1988;13:273–8.

    Article  CAS  Google Scholar 

  34. Escott GM, Adams DJ. Chitinase activity in human serum and leukocytes. Infect Immun. 1995;63:4770–3.

    PubMed Central  CAS  PubMed  Google Scholar 

  35. Frank S, Hubner G, Breier G, Longaker MT, Greenhalgh DG, Werner S. Regulation of vascular endothelial growth factor expression in cultured keratinocytes. Implications for normal and impaired wound healing. J Biol Chem. 1995;270:12607–13.

    Article  CAS  PubMed  Google Scholar 

  36. Chavakis T, Cines DB, Rhee JS, Liang OD, Schubert U, Hammes HP, Higazi AA, Nawroth PP, Preissner KT, Bdeir K. Regulation of neovascularization by human neutrophil peptides (alpha-defensins): a link between inflammation and angiogenesis. FASEB J. 2004;18:1306–8.

    CAS  PubMed  Google Scholar 

  37. Masuoka K, Ishihara M, Asazuma T, Hattori H, Matsui T, Takase B, Kanatani Y, Fujita M, Saito Y, Yura H, Fujikawa K, Nemoto N. Interaction of chitosan with fibroblast growth factor-2 and its protection from inactivation. Biomaterials. 2005;26:3277–84.

    Article  CAS  PubMed  Google Scholar 

  38. Kiyozumi T, Kanatani Y, Ishihara M, Saitoh D, Shimizu J, Yura H, Suzuki S, Okada Y, Kikuchi M. The effect of chitosan hydrogel containing DMEM/F12 medium on full-thickness skin defects after deep dermal burn. Burns. 2007;33:642–8.

    Article  PubMed  Google Scholar 

  39. Vesselov LM, Whittington W, Lilge L. Performance evaluation of cylindrical fiber optic light diffusers for biomedical applications. Laser Surg Med. 2004;34:348–51.

    Article  Google Scholar 

  40. Kaehler GF, Sold MG, Fischer K, Post S, Enderle M. Selective fluid cusion in the submucosal layer by water jet: advantage for endoscopic mucosal resection. Eur Surg Res. 2007;39:93–7.

    Article  CAS  PubMed  Google Scholar 

  41. Walker KJ, Madihally SV. Anisotropic temperature sensitive chitosan-based injectable hydrogels mimicking cartilage matrix. J Biomed Mater Res B Appl Biomater. 2014. doi:10.1002/jbm.b.33293.

    Google Scholar 

  42. Park MH, Moon HJ, Park JH, Shinde UP, Ko DY, Jeong B. PEG-poly (l-alanine) thermogel as a 3D scaffold of bone-marrow-derived mesenchymal stem cells. Macromol Biosci. 2014. doi:10.1002/mabi.201400426.

    Google Scholar 

  43. Ryu JH, Lee Y, Kong WH, Kim TG, Park TG, Lee H. Catechol-functionalized chitosan/puronic hydrogels for tissue adhesives and hemostatic materials. Biomacromolecules. 2011;12:2653–9.

    Article  CAS  PubMed  Google Scholar 

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Biomedical Engineering Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Masayuki Ishihara, Hidemi Hattori & Shingo Nakamura

  2. Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Isao Kumano

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  1. Masayuki Ishihara
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  4. Shingo Nakamura
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Correspondence to Masayuki Ishihara.

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Ishihara, M., Kumano, I., Hattori, H. et al. Application of hydrogels as submucosal fluid cushions for endoscopic mucosal resection and submucosal dissection. J Artif Organs 18, 191–198 (2015). https://doi.org/10.1007/s10047-015-0843-z

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  • DOI: https://doi.org/10.1007/s10047-015-0843-z

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