可吸收壳聚糖材料止血性能及其生物相容性研究
[Abstract]:Chitosan is a product of chitin partial deacetylation. It has many advantages, such as hemostasis, antibacterial, wound healing and good biocompatibility. It is widely used in the tissue engineering fields such as vascular scaffold and wound repair. At present, chitosan based hemostat has been a great success, and its excellent coagulation effect is verified in military and civil fields. However, FD The application of the existing chitosan based hemostat approved by A is only external and can not be implanted in the body for a long time as an absorbable hemostat. Research shows that the existing chitosan based hemostat has two problems: (1) most of them are acidic, and they can lead to acute inflammatory reaction and chronic inflammation after implantation in animals and affect the trauma. Healing; (2) slow degradation, resulting in tissue adhesions, fibrous cysts and other side effects, and forming severe scar tissue. To make the chitosan material as an absorbable hemostatic material to be implanted in the body, these two existing defects must be solved.
(1) by systematic study of the regulation of chitosan molecular weight and deacetylation degree on the degradation rate of chitosan, a series of small molecular weight chitosan with a heavy average molecular weight of 36537-529652 was prepared by means of homogeneous oxidation degradation and heterogeneous oxidation degradation. The deacetylation degree of chitosan was prepared by chitin deacetylation and chitosan acetylation. A series of low deacetylation degree chitosan (acid-base titration) from 39.6% to 59.6%. The results of in vitro lysozyme degradation of chitosan showed that the degradation rate of chitosan was 39.6% faster than that of gelatin sponge.
(2) an innovative handmade papermaking process was proposed. Starting from the chitosan hydrogel suspension, using the capillary action and the hydrogen bond between the chitosan hydrogel particles, the chitosan porous membrane and the porous sponge were prepared by high temperature drying or one freeze drying. The chitosan porous membrane was formed in shape and soft. The chitosan porous sponge has high porosity and high surface roughness. This high porosity and high surface roughness can help to promote blood coagulation.
(3) the procoagulant properties of pure chitosan with different deacetylation degree were measured by dynamic coagulation in vitro, in which the effect of M0D3 (D.D=48.07%, IR) was the best. The coagulation mechanism of chitosan was preliminarily studied by means of platelet adsorption, red cell adsorption, APTT and TT test. Chitosan was mainly used to promote the adsorption of platelets and red blood cells. Blood coagulation;
(4) a new chitosan sponge with a degree of deacetylation of 39.6%, 48.07% and 93.6% was carried out in the rat liver trauma test. The results showed that the self-made chitosan sponge had hemostatic effect in the animal body. All chitosan sponges had better hemostatic effect than gelatin sponge. The total amount of bleeding was less than that of Gelfoam group, and the degree of deacetylation of the chitosan sponge was 48.3%. The hemostatic effect of chitosan is the best.
(5) the deacetylation degree was 39.6%, 48.07% and 93.6% (acid-base titration), the new chitosan sponge and gelatin sponge were implanted in the rat liver trauma site. The liver tissue specimens of rats were collected at 1 weeks, 4 weeks, 8 weeks and 24 weeks respectively. HE.Masson's staining and immunohistochemical staining (TGF- beta 1 and IL-1p) were used to examine the absorption and inflammation of various materials. The results showed that the chitosan was completely absorbed at eighth weeks when the degree of deacetylation was 39.6%; the total absorption time of the gelatin sponge was more than 8 weeks and completely absorbed at 24 weeks. The chitosan with deacetylation of 48.07% and 93.6% was not completely absorbed at 24 weeks. Pathological section and IL-1 beta staining showed that the degree of deacetylation was 39.6% of the shell. The inflammatory reaction was the weakest in the body, and the degree of deacetylation of chitosan TGF- beta 1 was low, the amount of collagen production was moderate, and no scar healing was formed; and the degree of deacetylation of chitosan was 39.6%, reducing the risk of adhesion of other tissues.
【学位授予单位】:浙江大学
【学位级别】:博士
【学位授予年份】:2013
【分类号】:O636.1;R318.08
【共引文献】
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