Investigation of The Wound Healing Effects of Chitosan on FGFR3 and VEGF Immunlocalization in Experimentally Diabetic Rats
International Journal of Biomedical Materials Research
Volume 1, Issue 1, June 2013, Pages: 1-8
Received: Apr. 17, 2013;
Published: May 20, 2013
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Z. Deniz Sahın Inan, Department of Histology and Embryology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey
Serpil Unver Saraydın, Department of Histology and Embryology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey
Chitosan is a naturally occurring substance that stimulates correct deposition, assembly and orientation of collagen fibres in extracellular matrix components in wounds and promotes migration of inflammatory cells. Fibroblast growth factor (FGF) is one of the most important growth factors playing crucial roles in angiogenesis and wound healing. Biologically, it acts via binding to the cellular surface receptors. FGFR3 is one of the most important receptors. Therefore the aim of the present study was to investigate, histologically and histochemically, the effect of chitosan on wound healing in experimentally diabetic rats divided into four groups. When compared to the diabetic and the control groups, chitosan group had more inflammatory cells, endothelial cells, newly formed blood vessels and reticular – collagen fibres in the wound healing area from the third day of operation.Moreover, in Chitosan Group, stronger VEGF and FGFR3 immunolo-calizations were evident and all steps of wound healing process were more regular. FGFR3 antibody used in this study had been tested only on diabetic wound healing. In conclusion, we have concluded that application of chitosan was essential to accelarate wound healing process in diabetic patients
Z. Deniz Sahın Inan,
Serpil Unver Saraydın,
Investigation of The Wound Healing Effects of Chitosan on FGFR3 and VEGF Immunlocalization in Experimentally Diabetic Rats, International Journal of Biomedical Materials Research.
Vol. 1, No. 1,
2013, pp. 1-8.
Komesu MC, Tanga MB, Buttros KR, et al (2004)Effects of acute diabetes on rat cutaneous wound healing. Pathophysi-ology 11:63–67.
Van Belle TL, Coppieters KT, Von Herrath MG (2011) Type 1 diabetes: etiology, immunology and therapeutic strategies. Physiol Rev. 91(1):79-118.
Brem H, Tomic-Canic M (2007) Cellular and molecular basis of wound healing in diabetes. The Journal of Clinical Invest.117 (5):1219–1222.
Pavlovic MD, Milenkovic T, Dinic M, et al (2007) The prevalence of cutaneous manifestations in young patients with IDDM. Diabetes Care 30(8):1964–1967.
Blakytny R, Jude EB, Martin G, et al (2000) Lack of insulin-like growth factor 1 (IGF1) in the basal keratinocyte layer of diabetic skin and diabetic foot ulcers. Journal of Pathology 190(5):589–59.
Jude EB, Blakytny R, Bulmer J, et al (2002) Transforming growth factor-beta 1, 2, 3 and receptor type I and II in dia-beticfoot ulcers. Diabetic Medicine 19(6):440–447.
Blakytny R, Jude E (2006) The molecular biology of chronic wounds and delayed healing in diabete. Diabetic Medicine 23(6):594-608.
Szkudelski T (2001) The mechanism of alloxan and strepto-zotocin action in B cells of the rat pancreas. Physiol Res. 50:536–46.
Baum CL,Arpey J (2005) Normal cutaneous wound healing: clinical Correlation with Cellular and Molecular Events. Dermatolologic Surgery 31(6):674-686.
Cupp CL, Bloom DC ( 2002)Gene therapy, electroporation, and the future of wound-healing therapies. Facial Plast Surg 18:53-7.
Man LX, Park JC, Terry MJ et al (2005) Lentiviral gene therapy with platelet-derived growth factor B sustains ac-celerated healing of diabetic wounds over time. Ann Plast Surg 55:81.
Nagai MK, Embil JM (2003) Becaplermin: Recombinant platelet derived growth factor, a new treatment for healing diabetic foot ulcers. Expert Opin Biol Ther 2:2-11.
Saraydin D, Koptagel E, Unver-Saraydin S, Karadag E, Guven O (2001). In vivo biocompatibility of radiation in-duced acrylamide and acrylamide/maleic acid hydrogels. Journal of Materials Science 36(10):2473-2481.
Saraydin D, Unver-Saraydin S, Karadag E, Koptagel E,Guven O (2004). In vivo biocompatibility of radiation crosslinked acrylamide copolymers. Nuclear Instruments and Methods 217:281-292.
Unver-Saraydin S, Bulut HE, Ozüm Ü, nan Sahin ZD, Polat ZA, Yalman Y, Saraydin D (2011). Evaluation of the cytotoxic effects of various monomers in vitro also their ef-fects apoptosis and GFAP immunolocalization in rat spinal cord in vivo. HealthMED 5(1):17-28.
Unver-Saraydin S, Saraydin D (2011). Histopathological effect characteristics of various biomaterials and monomers used in polymeric biomaterial production in biomaterials. Physics and Chemistry, edited by: Rosario Pignatell In Tech.
Illum L (1998). Chitosan and its use as a pharmaceutical excipient. Pharm Res 15:326-1331.
Ravikumar MNV (2000) A review of chitin and chitosan applications. Reactive and Functional Polymers 46:1–27.
Shigemasa Y, Minami S (1995) Applications of chitin and chitosan for biomaterials. Biotechnology and Genetic Engi-neering Reviews 13:383-420.
Singla AK, Chawla M (2001)Chitosan: some pharmaceutical and biological aspects-an update J. Pharm. Pharmacol 53:1047-1067.
Ueno H, Mori T, Fujinaga T (2001) Topical formulations and wound healing applications of chitosan Adv. Drug. Del. Rev 52:105–115.
Okamoto Y, Shibazaki K, Minami S et al (1995) Evaluation of chitin and chitosan on open wound healing in dogs. J. Vet. Med. Sci. 57:851–854.
Alemdaroglu C, Degim Z, Celebi N et al (2006) An investi-gation on burn wound healing in rats with chitosan geL formulation containing epidermal growth factor. Burns 32: 319-327.
Gavard J, Gutkind JS (2006)VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent en-docytosis of VE-cadherin. Nat Cell Biol. 8:1223-1228.
Barkovic A, Sirois MG (2007)Vascular permeability induced by VEGF family members in vivo: Role of endogenous PAF and NO synthesis. J Cell Biochem. 100:707-210.
Bao P, Kodra A,Tomic-Canic BAMet al (2008) The role of vascular endothelial growth factor in wound healingdoi: 10.1016/j. jss. 04. 023.
Jazwa A, Kucharzewska P,Leja J et al (2010) Combined vascular endothelial growth factor A and fibroblast growth factor gene transfer improves wound healing in diabetic mice. Genetic vaccines and Therapy 8(6): 2-16.
Falanga V (2005) Wound healing and its impairment in the diabetic foot. Lancet 366(9498):1736-1743
Doxey DL, Ng MC, Dill RE, Iacopino AM (1995) Platelet-derived growth factor levels in wounds of diabetic rats. Life Sci. 57(11):1111-1123
Turan M, Saraydin US, Bulut E et al (2004)Do vascular endothelial growth factor and basic fibroblast growth factor promote phenytoin’s wound healing effect in rat? An im-munohistochemical and histopathologic study. Dermatol Surg. 30:1303–1309.
Suhardja A, Hoffman H (2003) Role of growth factors and their reseptors in proliferation of microvascular endothelial cells. Microscopy Research and Technique 60:70-75.
Hughes SE (1997) Differantial expression of the fibroblast growth factor receptor (FGFR) multigene family in normal human adult tissues. J Histochem Cytochem.45(7):1005-1019.
Takenaka H, Yasuno H, Kishimoto S (2002) Immunolocali-zation of fibroblast growth factor receptors in normal and wounded human skin. Arch Dermatol Res. 294:331–338.
Karabay G, Zayapan R, Take G (2006) Streptozotosinle oluturulan diabetin sçan periferik sinirleri üzerine etkisinin elektron mikroskobik incelenmesi. Uluda Üniversitesi Tp Fakültesi Derg. 32(3):77-81.
Saeed MK, Deng Y, Dai R (2008) Attenuation ofibiochemi-cal parameters in streptozotocin-induced rats by oral ad-ministration of extracts and fractions of Cephalotaxus sinensis. J Clin Biochem Nutr. 42:21–32.
Chen XG, Liu CS, Liu CG et al (2006) Preparation and biocompatibility of chitosan microcarriers as biomaterial. Biochemical Engineering Journal27:269–274.
Atiba A, Ueno H (2010) The effect of Aloe Vera oral ad-ministration on cutaneous wound healing in type 2 diabetic rats. J Vet Med Sci. doi:10.1292/jvms.10-0438.
Brem H, Tomic-Canic M (2007) Cellular and molecular basis of wound healing in diabetes. The Journal of Clinical Invest. 117(5):1219–1222.
Pavlovic MD, Milenkovic T, Dinic M et al (2007)The prevalence of cutaneous manifestations in young patients with IDDM.Diabetes Care 30(8):1964–1967.
Nigalaye AG, Adusumuli P, Bolton S (1990) Investigation of prolonged drug release from matrix formulations of chi-tosan. Drug Dev Ind Pharm. 16:449-467.
Rao SB and Sharma CP (1997)Use of chitosan as a bioma-terial: Studies on its safety and hemostatic potential. J Biomed Mater Res. 34:21-28.
Acosta JB, Barco DG, Vera DC et al (2008) The proin-flammatory environment in recalcitrant diabetic foot wounds.International Wound Journal 5:530–630.
Sabine AE, Thomas K, JeffreyMD (2007)Inflammation in wound repair: Molecular and cellular mechanisms. Journal of Investigative Dermatology 127:514–525.
Martin P and Leibovich S J (2005)Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol. 15:599-607.
Olsson AK, Dimberg A, Kreugeret al (2006) VEGF receptor signalling–in control of vascular function. NatRev Mol Cell7:359-564.
Banks RE, Forbes MA, Kinsey SE et al (1998) Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: Significance for VEGF measure-ments and cancer biology. Br J Cancer 77:956–960.
Miyagami M, Katayama Y (2005) Angiogenesis of glioma: evaluation of ultrastructural characteristics of microvessels and tubular bodies (Weibel–Palade) in endothelial cells and immunohistochemical findings with VEGF and p53 protein. Med Mol Morphol. 38:36–42.
Nogam M, Hohi T, Kinoshita M et al (2007) Vascular endothelial growth factor expression in rat skin incision wound. Med Mol Morphol. 40:82–87.
Nissen NN, Polverini PJ, Koch AE et al (1998) Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol. 152:1445-1450.
Altavilla D, Saitta A, Cucinotta D et al (2001) Inhibition of lipid peroxidation restores impaired vascular endothelial growth factor expression and stimulates wound healing and angiogenesis. Diabetes 50:667–670.
Ueno H, Yamada H, Tanaka I et al (1999). Accelerating effects of chitosan for healing at early phase of experimental open wound in dogs. Biomaterials 20:1407–14.
Komi-Kuramochi A, Kawano M, Oda Y et al (2005) Ex-pression of fibroblast growth factors and their receptors dur-ing full-thickness skin wound healing in young and aged mice. Journal of Endocrinology 186:273–289.