Journal of Materials Science: Materials in Medicine

, Volume 24, Issue 11, pp 2549–2559 | Cite as

Influence of the carboxymethyl chitosan anti-adhesion solution on the TGF-β1 in a postoperative peritoneal adhesion rat

  • Zengjuan Zheng
  • Weifen Zhang
  • Weiqing Sun
  • Xiaojian Li
  • Jinghua Duan
  • Juanjuan Cui
  • Zhanqin Feng
  • Heidi M. Mansour


The aim of this paper was to investigate the effect of carboxymethyl chitosan anti-adhesion solution on prevention of postsurgical adhesion. Forty adult male Wistar rats were randomly divided into three groups: 0.9 % normal saline solution (group A), hyaluronic acid gels (group B) and carboxymethyl chitosan anti-adhesion solution (group C). The animals were treated with normal saline, hyaluronic acid gels or carboxymethyl chitosan anti-adhesion solution at the time of surgery. After 2 or 3 weeks, the degree of adhesions and histological effects were determined. The adhesions in groups B and C were significantly decreased, and the levels of TGF-β1 and hydroxyproline in group C were significantly lower than that in group A (P < 0.05). The histopathology in group C showed fewer inflammatory cells and fibroblasts. Carboxymethyl chitosan anti-adhesion solution can effectively prevent postoperative adhesion which is a promising drug delivery system in the context of postsurgical anti-adhesion.


  1. 1.
    Yang B, Gong CY, Zhou ST, Li Z, Qi X, Zhong Q, Luo F, Qian Z. Preventing postoperative abdominal adhesions in a rat model with PEG-PCL-PEG hydrogel. Int J Nanomed. 2012;7:547–57.Google Scholar
  2. 2.
    Kutlay J, Ozer Y, Isik B, Kargici H. Comparative effectiveness of several agents for preventing postoperative adhesions. World J Surg. 2004;28:662–5.CrossRefGoogle Scholar
  3. 3.
    Mulier KE, Nguyen AH, Delaney JP, Marquez S. Comparison of Permacol™ and Strattice™ for the repair of abdominal wall defects. Hernia. 2011;15(3):315–9.CrossRefGoogle Scholar
  4. 4.
    Sahin M, Cakir M, Avsar FM, Tekin A, Kucukkartallar T, Akoz M. The effects of anti-adhesion materials in preventing postoperative adhesion in abdominal cavity (anti-adhesion materials for postoperative adhesions). Inflammation. 2007;6:244–9.CrossRefGoogle Scholar
  5. 5.
    Wei CZ, Hou CL, Gu QS, Jiang LX, Zhu B, Sheng AL. A thermosensitive chitosan-based hydrogel barrier for post-operative adhesions’ prevention. Biomaterials. 2009;30:5534–40.CrossRefGoogle Scholar
  6. 6.
    Na NH, Kim IK, Han JH, Lee JG, Ton TI, Han DK, Ito Y, Song KS, Jang EC. Synthesis of O-carboxylated low molecular chitosan with azido phenyl group: its application for adhesion prevention. Macromol Res. 2010;10:1001–7.CrossRefGoogle Scholar
  7. 7.
    Lauder CI, Garcea G, Strickland A, Maddern GJ. Use of a modified chitosan-dextran gel to prevent peritoneal adhesions in rat model. J Surg Res. 2011;171:877–82.CrossRefGoogle Scholar
  8. 8.
    Muzzarelli RAA, Muzzarelli C. Chitosan chemistry: relevance to the biomedical sciences. Adv Polym Sci. 2005;186:151–209.CrossRefGoogle Scholar
  9. 9.
    Francesko A, Tzanov T. Chitin, chitosan and derivatives for wound healing and tissue engineering. Adv Biochem Eng Biotechnol. 2011;125:1–27.Google Scholar
  10. 10.
    Park SH, Seo SY, Na NH, Kim KL, Lee JW, Woo HD, Lee JH, Seok HK, Lee JG, Chung SI, Chung KH, Han DK, Ito Y, Jang EC, Son TI. Preparation of a visible light-reactive low molecular-O-carboxymethyl chitosan (LM-O-CMCS) derivative and applicability as an anti-adhesion agent. Macromol Res. 2011;9:921–7.CrossRefGoogle Scholar
  11. 11.
    Jiang LY, Li YB, Xiong CD. A novel composite membrane of chitosan-carboxymethyl cellulose polyelectrolyte complex membrane filled with nano-hydroxyapatite. I. Preparation and properties. J Mater Sci Mater Med. 2009;20:1645–52.CrossRefGoogle Scholar
  12. 12.
    Zhang ZP, Zhou GW, Wu HP, Zhang DB, Shi RL, Pan YL. Experimental study on carboxymethyl chitosan in preventing peritoneal adhesion in rats. J Clin Res. 2010;27:101–4.Google Scholar
  13. 13.
    Daroz LRD, Lopes JB, Dallan LAO, Filho SPC, Moreira LFP, Stolf NAG. Prevention of postoperative pericardial adhesions using thermal sterile carboxymethyl chitosan. Rev Bras Cir Cardvasc. 2008;23(4):480–7.CrossRefGoogle Scholar
  14. 14.
    Kennedy R, Costain DJ, Mcalister VC, Lee TDG. Prevention of experiment postoperative peritoneal adhesions by N,O-carboxylmethyl chitosan. Surgery. 1996;120(5):866–70.CrossRefGoogle Scholar
  15. 15.
    Lou W, Zhang H, Ma J, Zhang D, Liu C, Wang S, Deng Z, Xu H, Liu J. In vivo evaluation of in situ polysaccharide based hydrogel for prevention of postoperative adhesion. Carbohydr Polym. 2012;90(2):1024–31.CrossRefGoogle Scholar
  16. 16.
    Zhou J, Elson C, Lee TD. Reduction in postoperative adhesion formation and re-formation after an abdominal operation with the use of N,O-carboxymethyl chitosan. Surgery. 2004;135(3):307–12.CrossRefGoogle Scholar
  17. 17.
    Wang D, Mo J, Pan S, Chen H, Zhen H. Prevention of postoperative peritoneal adhesions by O-carboxymethyl chitosan in a rat cecal abrasion model. Clin Invest Med. 2010;33(4):E254–60.Google Scholar
  18. 18.
    Harris ES, Morgan RF, Rodeheaver GT. Analysis of the kinetics of peritoneal adhesion formation in the rat and evaluation of potential antiadhesive agents. Surgery. 1995;117:663–9.CrossRefGoogle Scholar
  19. 19.
    Nair SK, Bhat IK, Aurora AL. Role of proteolytic enzyme in the prevention of postoperative intraperitoneal adhesions. Arch Surg. 1974;108:849–53.CrossRefGoogle Scholar
  20. 20.
    Dong W, Han B, Feng Y, Song F, Chang J, Jiang H, Tang Y, Liu W. Pharmacokinetics and biodegradation mechanisms of a versatile carboxymethyl derivative of chitosan in rats: in vivo and in vitro evaluation. Biomacromolecules. 2010;11(6):1527–33.CrossRefGoogle Scholar
  21. 21.
    Ryan CK, Sax HC. Evaluation of a carboxymethylcellulose sponge for prevention of postoperative adhesions. Am J Surg. 1995;169(1):154–9.CrossRefGoogle Scholar
  22. 22.
    Chang J, Thunder R, Most D, Longaker MT, Lineaweaver WC. Studies in flexor tendon wound healing: neutralizing antibody to TGF-beta1 increases postoperative range of motion. Plast Reconstr Surg. 2000;105(1):148–55.CrossRefGoogle Scholar
  23. 23.
    Lopes JB, Dallan LA, Moreira LF, Campana Filho SP, Gutierrez PS, Lisboa LA, de Oliveira SA, Stolf NA. Synergism between keratinocyte growth factor and carboxymethyl chitosan reduces pericardial adhesions. Ann Thorac Surg. 2010;90(2):566–72.CrossRefGoogle Scholar
  24. 24.
    Trowbridge JM, Rudisill JA, Ron D, Gallo RL. Dermatan sulfate binds and potentiates activity of keratinocyte growth factor (FGF-7). J Biol Chem. 2002;277(45):42815–20.CrossRefGoogle Scholar
  25. 25.
    Jiang D, Xu C, Li Z, Zhang Y, Han F, Jiang Z. Protective action of hepatocyte growth factor on transforming growth factor beta-1-induced alpha-smooth muscle actin and extracellular matrix in cultured human peritoneal fibroblasts. Med Sci Monit. 2010;16(8):BR250–4.Google Scholar
  26. 26.
    Hong X, Shen BY, Han BS. Study on the effect of carboxymethyl-chitosan in the prevention of postoperative abdominal adhesion and its mechanism of action. J Surg Concepts Pract. 2009;14:426–9.Google Scholar
  27. 27.
    Zhou J, Liwski RS, Elson C, Lee TD. Reduction in postsurgical adhesion formation after cardiac surgery in a rabbit model using N, O-carboxymethyl chitosan to block cell adherence. Thorac Cardiovasc Surg. 2008;135(4):777–83.CrossRefGoogle Scholar
  28. 28.
    Pan SR, Chen HF, Mo JC, Wang DJ, Zhang W, Zhang HL. Experimental Study on carboxymethyl chitosan used for prevention of postsurgical adhesions. Chin J Biomed Eng. 2006;25(3):277–82.Google Scholar
  29. 29.
    Filippo CD, Petronella P, Freda F, Scorzelli M, Ferretti M, Canonico S, Rossi F, D’Amico M. Involvement of the ubiquitin-proteasome system in the formation of experimental postsurgical peritoneal adhesions. Mediat Inflamm. 2012;2012:1–7.CrossRefGoogle Scholar
  30. 30.
    Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL. Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Dig Surg. 2001;18:260–73.CrossRefGoogle Scholar
  31. 31.
    Attard JA, MacLean AR. Adhesive small bowel obstruction: epidemiology, biology and prevention. Can J Surg. 2007;50:291–300.Google Scholar
  32. 32.
    Axel S, Joachim B, Kasper O, Weiß J, Schmidt W, Rolle U. Experimental study evaluating the effect of a barrier method on postoperative intraabdominal adhesions. Dig Dis Sci. 2006;51(3):566–70.CrossRefGoogle Scholar
  33. 33.
    Yang Z, Han BQ, Fu DW, Liu W. Acute toxicity of high dosage carboxymethyl chitosan and its effect on the blood parameters in rats. J Mater Sci Mater Med. 2012;23:457–62.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Zengjuan Zheng
    • 1
  • Weifen Zhang
    • 1
  • Weiqing Sun
    • 2
  • Xiaojian Li
    • 3
  • Jinghua Duan
    • 3
  • Juanjuan Cui
    • 1
  • Zhanqin Feng
    • 1
  • Heidi M. Mansour
    • 3
  1. 1.College of Pharmacy and Biological Science, Weifang Medical UniversityWeifangPeople’s Republic of China
  2. 2.Hangzhou Singclean Medical Products Co., Ltd.HangzhouPeople’s Republic of China
  3. 3.Drug Development Division, Department of Pharmaceutical SciencesCollege of Pharmacy, University of KentuckyLexingtonUSA

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