Preparation And Biomedical Research Of Injectable Polysaccharide Hydrogel

Injectable hydrogel is a kind of materials which could be injected by solution state and then formed gel state after a phase transition. When employed as wound dressing,injectable hydrogels could form in situ by physical or chemical crosslinking methods, and closely contact with the wound sites, and keep humid environment needed during the period of wound healing. In addition, the porous structure of hydrogels benefits gas exchange and nutrients transport between the wound sites and the outside, absorption of exudate, and promtes cell migration and skin regeneration. Injectable hydrogels loading drug coule be applied for local treatment, which have the advantage in maintaining long-term exposure between the medicine and administration site, improving the bioavailability, controlling drug release. Therefore, they have attracted much attention in the field of drug carrier. The natural polysaccharide are used as initial material in this paper.The polysaccharide injectable hydrogels was prepared by schiff base reaction, and the toxic crosslinkers needn’t to be introduceed. Moreover, the hydrogel could form under physiological conditions. We focus on studying the application of the polysaccharide hydrogel in burn treatment and preventing postoperative infection. The main content of the paper and conclusions are as follows:(1) The study of the polysaccharide hydrogel scaffold as burn healing: water-soluble carboxymethyl chitosan(CMC) were prepared by the free radical reaction. The oxidized dextran were successfully prepared by the oxidation of sodium periodate. When fixed polysaccharide concentrations, we have researched the effect of CMC/Odex content ratio with on the gelation time.The results suggested that the gelation time is in favour to animal experiment when the 3% CMC/Odex content ratio kept at 2/1. Rheological results showed higer the storage modulus of the hydrogel. Scanning electron microscopy(SEM) were applied to observe the morphology of hydrogels. The porous structure was found, which benefits retainning moisture and promoting burn wound healing. In vitro degradation of hydrogels exhibited slow mass loss and about 50% of the hydrogel degradated in a month.The results of MTT method preliminary showed that the hydrogels have no obvious cytotoxicity.Besides, the LIVE/DEAD assay further confirmed that the hydrogels possess excellent cytocompatibility. Moreover, the adhesion experiment showed that the hydrogels with CMC/Odex certain content ratio(2/1) is conducive to cell adhesion. Subssequently,the deep second degree burn model was established and treated, followed by the H&E and Masson staining. The macroscopic evaluation and histological analysis displayed that the polysaccharide hydrogels have promoted burn healing.(2) The study of the polysaccharide hybrid hydrogel as drug carrier in the application of preventing postoperative infection: Based on the previous research, we successful prepared the carboxymethyl chitosan and oxidized dextran, which were formed into hydrogel crosslinked by schiff’s base reaction. The higher the concentration of polymer concentration and carboxymethyl chitosan component content, the shorter gelation time.Additionally, rheological results revealed that the storage modulus was strengthed when increased the polymer concentration. Morover, the content ratio have little influence on the storage modulus of the hydrogel when kept a certain concentration. We selected 3%CMC/Odex(v/v = 1:1) hydrogel as drug carrier for the study in vivo. Scanning electron microscopy(SEM) were applied to observe morphology of hydrogels, a kind of porous structure. In addition, the polysaccharide hydrogels degradated slowly in vitro. In vitro drug release were conducted and displayed slow-release of ceftriaxone after loaded in the hydrogels. The drug loaded hydrogel were used in vitro antibacterial test. And the obvious bacteriostatic ring appeared surrounding the drug loded hydrogels while no bacteriostatic ring formed in the control group, suggesting the remarkable aitibacterial property. The results of MTT test and LIVE/DEAD assay have proved that the materials and hydrogels have no significant cytotoxicity. Furthermore, we succeed in establishing subcutaneous infection infection model and cecal ligation and puncture(CLP) model, the macroscopic observation and histological analysis showed drug loaded hydrogels have a significant therapeutic effect for preventing postoperative infection.