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Endoscopic application of EGF-chitosan hydrogel for precipitated healing of GI peptic ulcers and mucosectomy-induced ulcers

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Abstract

The gastrointestinal (GI) endoscopy has become a standard diagnostic tool for GI ulcers and cancer. In this study we studied endoscopic application of epidermal growth factor-containing chitosan hydrogel (EGF-CS gel) for treatment of GI ulcer. We hypothesized that directional ulcer-coating using EGF-CS gel via endoscope would precipitate ulcer-healing. EGF-CS gel was directly introduced to the ulcer-region after ulceration in acetic acid-induced gastric ulcer (AAU) and mucosal resection-induced gastric ulcer (MRU) rabbit and pig models. The ulcer dimensions and mucosal thicknesses were estimated and compared with those in the control group. Healing efficacy was more closely evaluated by microscopic observation of the ulcer after histological assays. In the AAU model, the normalized ulcer size of the gel-treated group was 2.3 times smaller than that in the non-treated control group on day 3 after ulceration (P < 0.01). In the MRU model, the normalized ulcer size of the gel-treated group was 5.4 times smaller compared to that in the non-treated control group on day 1 after ulceration (P < 0.05). Histological analysis supported the ability of EGF-CS gel to heal ulcers. The present study suggests that EGF-CS gel is a promising candidate for treating gastric bleeding and ulcers.

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References

  1. Shaheen NJ, Hansen RA, Morgan DR, Gangarosa LM, Ringel Y, Thiny MT, et al. The burden of gastrointestinal and liver diseases. Am J Gastroenterol. 2006;101(9):2128–38.

    Article  Google Scholar 

  2. Chai J, Baatar D, Tarnawski A. Serum response factor promotes re-epithelialization and muscular structure restoration during gastric ulcer healing. Gastroenterology. 2004;126(7):1809–18.

    Article  Google Scholar 

  3. Lockrey G, Lim L. Peptic ulcer disease in older people. J Pharm Pract Res. 2011;41(1):58–61.

    Google Scholar 

  4. Boers M, Tangelder MJ, van Ingen H, Fort JG, Goldstein JL. The rate of NSAID-induced endoscopic ulcers increases linearly but not exponentially with age: a pooled analysis of 12 randomised trials. Ann Rheum Dis. 2007;66(3):417–8.

    Article  Google Scholar 

  5. Holster IL, Kuipers EJ. Update on the endoscopic management of peptic ulcer bleeding. Curr Gastroenterol Rep. 2011;13(6):525–31.

    Article  Google Scholar 

  6. Gotoda T. Endoscopic resection of early gastric cancer. Gastric Cancer. 2007;10(1):1–11.

    Article  Google Scholar 

  7. Hayashi T, Matsuyama T, Hanada K, Nakanishi K, Uenoyama M, Fujita M, et al. Usefulness of photocrosslinkable chitosan for endoscopic cancer treatment in alimentary tract. J Biomed Mater Res B Appl Biomater. 2004;71(2):367–72.

    Article  Google Scholar 

  8. Kumano I, Ishihara M, Nakamura S, Kishimoto S, Fujita M, Hattori H, et al. Endoscopic submucosal dissection for pig esophagus by using photocrosslinkable chitosan hydrogel as submucosal fluid cushion. Gastrointest Endosc. 2012;75(4):841–8.

    Article  Google Scholar 

  9. Hattori H, Amano Y, Nogami Y, Takase B, Ishihara M. Hemostasis for severe hemorrhage with photocrosslinkable chitosan hydrogel and calcium alginate. Ann Biomed Eng. 2010;38(12):3724–32.

    Article  Google Scholar 

  10. Ishizuka T, Ishihara M, Aiko S, Nogami Y, Nakamura S, Kanatani Y, et al. Experimental evaluation of photocrosslinkable chitosan hydrogel as injection solution for endoscopic resection. Endoscopy. 2009;41(1):25–8.

    Article  Google Scholar 

  11. Saito Y, Uraoka T, Matsuda T, Emura F, Ikehara H, Mashimo Y, et al. Endoscopic treatment of large superficial colorectal tumors: a case series of 200 endoscopic submucosal dissections (with video). Gastrointest Endosc. 2007;66(5):966–73.

    Article  Google Scholar 

  12. Tsuda Y, Ishihara M, Amako M, Arino H, Hattori H, Kanatani Y, et al. Photocrosslinkable chitosan hydrogel can prevent bone formation in both rat skull and fibula bone defects. Artif Organs. 2009;33(1):74–7.

    Article  Google Scholar 

  13. Tsuda Y, Hattori H, Tanaka Y, Ishihara M, Kishimoto S, Amako M, et al. Ultraviolet light-irradiated photocrosslinkable chitosan hydrogel to prevent bone formation in both rat skull and fibula bone defects. J Tissue Eng Regen Med. 2013;7(9):720–8.

    Article  Google Scholar 

  14. Ueno H, Yamada H, Tanaka I, Kaba N, Matsuura M, Okumura M, et al. Accelerating effects of chitosan for healing at early phase of experimental open wound in dogs. Biomaterials. 1999;20(15):1407–14.

    Article  Google Scholar 

  15. Peluso G, Petillo O, Ranieri M, Santin M, Ambrosio L, Calabro D, et al. Chitosan-mediated stimulation of macrophage function. Biomaterials. 1994;15(15):1215–20.

    Article  Google Scholar 

  16. Muzzarelli R, Tarsi R, Filippini O, Giovanetti E, Biagini G, Varaldo PE. Antimicrobial properties of N-carboxybutyl chitosan. Antimicrob Agents Chemother. 1990;34(10):2019–23.

    Article  Google Scholar 

  17. Rask F, Dallabrida SM, Ismail NS, Amoozgar Z, Yeo Y, Rupnick MA, et al. Photocrosslinkable chitosan modified with angiopoietin-1 peptide, QHREDGS, promotes survival of neonatal rat heart cells. J Biomed Mater Res A. 2010;95(1):105–17.

    Article  Google Scholar 

  18. Ono K, Saito Y, Yura H, Ishikawa K, Kurita A, Akaike T, et al. Photocrosslinkable chitosan as a biological adhesive. J Biomed Mater Res. 2000;49(2):289–95.

    Article  Google Scholar 

  19. Ono K, Ishihara M, Ozeki Y, Deguchi H, Sato M, Saito Y, et al. Experimental evaluation of photocrosslinkable chitosan as a biologic adhesive with surgical applications. Surgery. 2001;130(5):844–50.

    Article  Google Scholar 

  20. Ong SY, Wu J, Moochhala SM, Tan MH, Lu J. Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties. Biomaterials. 2008;29(32):4323–32.

    Article  Google Scholar 

  21. Carpenter G, Cohen S. Epidermal growth factor. J Biol Chem. 1990;265(14):7709–12.

    Google Scholar 

  22. Brown GL, Curtsinger LJ, White M, Mitchell RO, Pietsch J, Nordquist R, et al. Acceleration of tensile strength of incisions treated with EGF and TGF-beta. Ann Surg. 1988;208(6):788–94.

    Article  Google Scholar 

  23. Celebi N, Erden N, Gonul B, Koz M. Effects of epidermal growth factor dosage forms on dermal wound strength in mice. J Pharm Pharmacol. 1994;46(5):386–7.

    Article  Google Scholar 

  24. Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys. 2004;59(2 Suppl):21–6.

    Article  Google Scholar 

  25. Celebi N, Turkyilmaz A, Gonul B, Ozogul C. Effects of epidermal growth factor microemulsion formulation on the healing of stress-induced gastric ulcers in rats. J Control Release. 2002;83(2):197–210.

    Article  Google Scholar 

  26. Alemdaroglu C, Degim Z, Celebi N, Zor F, Ozturk S, Erdogan D. An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth factor. Burns. 2006;32(3):319–27.

    Article  Google Scholar 

  27. Takahashi M, Ota S, Shimada T, Hamada E, Kawabe T, Okudaira T, et al. Hepatocyte growth factor is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture. J Clin Invest. 1995;95(5):1994–2003.

    Article  Google Scholar 

  28. de Carpani Kaski M, Rentsch R, Levi S, Hodgson HJ. Corticosteroids reduce regenerative repair of epithelium in experimental gastric ulcers. Gut. 1995;37(5):613–6.

    Article  Google Scholar 

  29. Kitajima T, Okuhira M, Tani K, Nakano T, Hiramatsu A, Mizuno T, et al. Cell proliferation kinetics in acetic acid-induced gastric ulcer evaluated by immunohistochemical staining of proliferating cell nuclear antigen. J Clin Gastroenterol. 1993;17(Suppl 1):S116–20.

    Article  Google Scholar 

  30. Sairam K, Priyambada S, Aryya NC, Goel RK. Gastroduodenal ulcer protective activity of Asparagus racemosus: an experimental, biochemical and histological study. J Ethnopharmacol. 2003;86(1):1–10.

    Article  Google Scholar 

  31. Relan NK, Fligiel SE, Dutta S, Tureaud J, Chauhan DP, Majumdar AP. Induction of EGF-receptor tyrosine kinase during early reparative phase of gastric mucosa and effects of aging. Lab Invest. 1995;73(5):717–26.

    Google Scholar 

  32. Wong WM, Playford RJ, Wright NA. Peptide gene expression in gastrointestinal mucosal ulceration: ordered sequence or redundancy? Gut. 2000;46(2):286–92.

    Article  Google Scholar 

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Acknowledgments

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A111060). The large animal study was supported by the National Center of Efficacy Evaluation for the Development of Health Products Targeting Digestive Disorders (NCEED).

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Correspondence to Don Haeng Lee or Su-Geun Yang.

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Jin Hee Maeng and Byoung Wook Bang contributed equally to this study.

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Maeng, J.H., Bang, B.W., Lee, E. et al. Endoscopic application of EGF-chitosan hydrogel for precipitated healing of GI peptic ulcers and mucosectomy-induced ulcers. J Mater Sci: Mater Med 25, 573–582 (2014). https://doi.org/10.1007/s10856-013-5088-x

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  • DOI: https://doi.org/10.1007/s10856-013-5088-x

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