Preparation of water-soluble chitosan/heparin complex and its application as wound healing accelerator.

To make effective wound healing accelerator, water-soluble chitosan (WSC)/heparin (CH) complex was prepared using WSC with wound healing ability and heparin with ability to attract or bind growth factor related to wound healing process. Water-soluble CH complex was prepared by the reaction between WSC and heparin, and then, by adding distilled water to it, ointment type with high viscosity was made. To evaluate the wound healing effect, full thickness skin excision was performed on the backs of the rat and then WSC and water-soluble CH complex ointments were applied in the wounds, respectively. After 15 days, gross and histologic examination was performed. Grossly, untreated control group revealed that the wound had well defined margin and was covered by crust. The second group treated with WSC ointment revealed small wound size with less amount of covering crust and ill-defined margin, which appeared to regenerate from margin. The third group treated with water-soluble CH complex ointment appeared to be nearly completely healed. Histology of each group was well correlated to gross findings. The third group shows nearly complete regeneration of appendage structure similar to normal in the dermis in contrast to control and second group with absence and less number of skin appendages, respectively.

[1]  D. Barritault,et al.  Heparan mimetic regulates collagen expression and TGF‐β1 distribution in gamma‐irradiated human intestinal smooth muscle cells , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  K. Rex,et al.  The effects of repeated doses of keratinocyte growth factor on cell proliferation in the cellular hierarchy of the crypts of the murine small intestine. , 2001, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[3]  R. Jirtle,et al.  EGF receptors of hepatocytes from rats treated with phenobarbital are sensitized to down-regulation by phenobarbital in culture. , 2000, Toxicology and applied pharmacology.

[4]  A. W. Nelson,et al.  Effect of chitin on nonwoven fabric implant in tendon healing , 1997 .

[5]  D. Kweon Preparation and characteristics of chitosan-g-PDMS copolymer , 1998 .

[6]  R. Thompson,et al.  Effects of heparin on wound healing. , 1972, Surgery, gynecology & obstetrics.

[7]  L. Nanney,et al.  Enhancement of wound healing by topical treatment with epidermal growth factor. , 1989, The New England journal of medicine.

[8]  M. Ruggiero,et al.  Antiproliferative effects of heparin on normal and transformed NIH/3T3 fibroblasts. , 1993, Cell biology international.

[9]  D. Rifkin,et al.  Interaction of heparin with human basic fibroblast growth factor: Protection of the angiogenic protein from proteolytic degradation by a glycosaminoglycan , 1989, Journal of cellular physiology.

[10]  E J Wood,et al.  The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro. , 2001, Biomaterials.

[11]  G. Evans,et al.  Heparin stimulates the proliferation of intestinal epithelial cells in primary culture. , 1994, Journal of cell science.

[12]  D. Gospodarowicz,et al.  Heparin protects basic and acidic FGF from inactivation , 1986, Journal of cellular physiology.

[13]  K. Kifune Clinical Application of Chitin Artificial Skin (Beschitin W) , 1992 .

[14]  G. Hansson,et al.  Human arterial smooth muscle cells in culture. Effects of platelet-derived growth factor and heparin on growth in vitro. , 1988, Experimental cell research.

[15]  A. Lane Human Fetal Skin Development , 1986, Pediatric dermatology.

[16]  I. Gouda,et al.  Heparin-chitosan complexes stimulate wound healing in human skin. , 1997, Scandinavian journal of plastic and reconstructive surgery and hand surgery.

[17]  P. Argenta,et al.  Scarless human fetal skin repair is intrinsic to the fetal fibroblast and occurs in the absence of an inflammatory response , 1994, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[18]  M. Tsukada,et al.  Physico-chemical properties of silk fibroin membrane as a biomaterial. , 1990, Biomaterials.

[19]  Z. Han,et al.  Glycosaminoglycans enhance human leukemic cell growth in vitro. , 1994, Leukemia research.

[20]  Yoshiharu Okamoto,et al.  Application of Chitin and Chitosan in Small Animals , 1992 .

[21]  J. McPherson,et al.  The influence of heparin on the wound healing response to collagen implants in vivo. , 1988, Collagen and related research.

[22]  Shiro Kobayashi,et al.  Determination of the degree of acetylation of chitin/chitosan by pyrolysis-gas chromatography in the presence of oxalic Acid. , 1998, Analytical chemistry.

[23]  B. Zederfeldt,et al.  The effect of high viscous dextran and heparin on wound healing. , 1968, Acta chirurgica Scandinavica.

[24]  Y. Okamoto,et al.  Chitin induces type IV collagen and elastic fiber in implanted non-woven fabric of polyester , 1996 .

[25]  J. Fang,et al.  Chitosan hydrogel as a base for transdermal delivery of berberine and its evaluation in rat skin. , 1999, Biological & pharmaceutical bulletin.

[26]  B. Casu,et al.  Structure and biological activity of heparin. , 1985, Advances in carbohydrate chemistry and biochemistry.

[27]  K. Kurita Chemistry and application of chitin and chitosan , 1998 .

[28]  S. Lim,et al.  Preparation and characteristics of a water‐soluble chitosan–heparin complex , 2003 .

[29]  Y. Okamoto,et al.  Evaluation of chitin and chitosan on open would healing in dogs. , 1995, The Journal of veterinary medical science.