| Chitosan is partially deacetylated from chitin and it has many fascinating biological properties such as hemostatic, anti-bacterial, and wound healing ability and good biocompatibility. Chitosan has been used widely in the tissue engineering field such as vascular stents reapir and wound repair. Chitosan-based hemostatic material achieved a great successand its excellent procoagulant effect has been proved in both military and civilian situations. However, the existing chitosan-based hemostatic materials have got FDA approval of applications only for external use, and are not recommended as absorbable hemostatic for long-term implantation. Studies showed that existing chitosan-based hemostatic materials have disadvantages:(1) Because of their acidic characteristic, they caused acute inflammation and chronic inflammation after in vivo implantation and hindered the wound healing process;(2) Slow degradation of them resulted in tissue adhesions, cystic fibrosis and other side effects, and formed a serious scar tissue. These shortcomings of chitosan should be overcome before it can be used as an absorbable hemostatic.(1) Chitosans with low molecular weight ranging from36537to529652were fabricated through oxydative degradation both in homogeneous and heterogeneous solution. And chitosans with low D.D (from39.6%to59.6%, acid base titration) were fabricated through deacetylation of chitin and acetylation of chitosan. Results of in vitro degradation by lysozyme showed that the chitosan with degree of deacetylation of40.07%was degraded fastest, even faster than the gelatin sponge.(2) By mimicing papermaking method, porous chitosan films and sponges were fabricated form chitosan hydrogel suspension after heating or freeze-drying. Hydrogel were crosslinked by capillary force and the formation of hydrogen bonds between the chitosan hydrogel particles. The resultant chitosan porous films are regular in shape, flexible and compliable to tissue surface; chitosan sponges have a high porosity and surface roughness in micrometer which will contribute to hemostatsis.(3) In vitro dynamic blood clotting test was carried out to study effect of o degree of deacetylation on procoagulant performance of chitosans. M0D3(DD=48.07%, acid base titration) showed maximum procoagulant effect on blood clotting among all chitosans. Besides, chitosan was found to activate the adhesion of platelet, red blood cells and white blood cell. Chitosan did not affect the blood parameters such as APTT and TT.(4) Chitosans sponges with degree of deacetylation of39.6%,48.07%and93.6%(acid base titration) achieved hemostasis in a rat liver trauma model.All chitosan sponge resulted in less total blood loss than gelatin sponges,and chitosan with degree of deacetylation of48.07%chitosan showed the best hemostatic effect.(5) Chitosan sponges with degree of deacetylation of39.6%,48.07%and93.6%and gelatin sponge were implanted in rat liver defects.1week,4weeks,8weeks and24weeks later, rats were sacrificed and implantation with surrounding liver tissues were collected and stained with H&E, Masson’s trichrome staining and immunohistochemical staining (TGF-β1and IL-1β). The absorption rate, inflammatory response and wound healing effects of various materials were compared. The results showed that chitosan with D.D of39.6%were completely absorbed after eight weeks of implantation; it took more than eight weeks for gelatin sponge to be completely absorbed and after24weeks of implantation, gelatin sponges were completely absorbed; chitosans with D.D of48.07%and93.6%lasted for24weeks. Biopsy and IL-1βstaining results showed that chitosan with D.D of39.6%showed weakest inflammatory response. Chitosan (D.D=39.6%) resulted in low level of of TGF-β1, moderate collagen depositon, and scarless wound healing. Moreover, chitosan(D.D=39.6%) reduced the chance of the adhesion to other organizations. |
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