Preparation Of Bacterial Cellulose-chitosan Composite Hydrogels And Its Application In Antibacterial Dressings And Drug Release

From a global perspective,with the development of economy and society as well as the continuous improvement of people’s living standards,people’s demands for biomedical materials are increasing sharply.Medical antibacterial dressings and drug carriers are the two major types of the materials that have attracted much attention.Although traditional dressings typical as cotton and medical gauze are cheap,easy to obtain and they can protect the wound surface and absorb exudate,however,they also have obvious disadvantages such as inability to wet the wound surface,easy penetration of bacteria,easy adhesion to the wound surface,and secondary trauma when changing the dressing.Therefore,the preparation of new dressings with antibacterial,wettability and biodegradability is an important direction for the development of this field.For chitin and chitosan drug sustained/controlled release carrier materials,their applications are limited to some extent due to inherent defects such as poor solubility,low mechanical strength of the materials and slow drug release rate.How to overcome its inherent shortcomings to develop a slow/controlled release system that meets the requirements of drug release and provides stable blood drug concentration is an urgent problem in this field.Bacterial cellulose（BC）has good water retention capacity,high purity,high crystallinity,excellent mechanical strength in wet state and good biocompatibility,which is considered to be one of the ideal raw materials for preparing medical polymer materials.Chitosan（CS）has many excellent properties,such as air permeability,water vapor permeability,biocompatibility,antibacterial properties and hemostatic properties,which has been received extensive attention in the field of dressings and drug release.Such natural polymers have always been favored in the field of biomedical materials.The new type of application-oriented medical polymer material can be created by compounding or blending,which can give full play to the advantages of a variety of biomass.However,simple physical blending can easily degrade the performance of composite materials due to phase separation.Therefore,the bacterial cellulose and chitosan are used as raw materials to prepare bacterial cellulose-chitosan composite hydrogels by in-situ chemical cross-linking in this thesis,and preliminarily explores its use in medical skin dressings and drug delivery through in vitro experiments.Applications.The research content of this article are as follows:（1）The BC was oxidized into dialdehyde-based bacterial cellulose（OBC）using different concentrations of Na IO₄ solution.Then OBC was placed in chitosan solutions of different concentrations for in-situ cross-linking to obtain bacterial cellulose-chitosan composite hydrogel（BCCS）.The thermodynamic properties,chemical structure,morphological characteristics and mechanical properties of the hydrogel were analyzed by TGA,FTIR,SEM,elemental analysis and rheological testing methods.The results of elemental analysis showed that when the concentration of Na IO₄ was 0.4%（w/v）,the content of aldehyde groups in OBC was as high as 14.29mg/g.When the amount of CS is 2.0%（w/v）,the combined amount of CS in the corresponding BCCS hydrogel is 19.33%.FTIR characterization showed that the stretching vibration peak signal of C=N structure appeared near 1550cm^-1,indicating that the aldehyde group of OBC and the amino group of CS were cross-linked through Schiff base reaction.Characterized by a rotational rheometer,the frequency range was 0.1 rad/s-100 rad/s,and the results showed that the storage modulus（5KPa-9KPa）was much greater than the loss modulus（1KPa-2KPa）.This indicated that the prepared hydrogel was a good elastomer and had good mechanical strength.This conclusion provided the basis for the work of the following two parts.（2）The antibacterial properties of the aforementioned composite hydrogels are slightly insufficient due to the partial consumption of the amino groups in CS due to the crosslinking reaction.The diameter of the inhibition zone was only 12mm and the inhibition rate of the OD value test did not exceed 30%.Therefore,the original chemical deposition method is used to load nano-Zn O in the hydrogel.After testing,the inhibition zone of the gel can reach more than20mm and the inhibition rate exceeds 70%.The morphology,mechanics,chemical and physical properties of the hydrogel were studied by various characterization techniques,such as thermogravimetric analysis,infrared spectroscopy and field emission scanning electron microscope,etc.The results show that Zn O@BCCS hydrogel has good compressibility and thermal stability.The antibacterial and mechanical properties of the hydrogels were improved by adjusting the zinc oxide content.The results showed that the compressive strength of the zinc oxide hydrogels can reach up to 440KPa,which was 15 times that of BC.In the antibacterial test,the inhibitory rates of 0.05MZn O@BCCS hydrogel on Escherichia coli and Staphylococcus aureus were 78.9%and 77.6%,respectively.In vitro toxicity experiments show that the hydrogel has no cytotoxicity.Based on the above results,it could be seen that the hydrogel had good mechanical properties and excellent antibacterial properties,so it was expected to be a new type of biodegradable antibacterial dressing to replace traditional dressings.（3）In addition,BC and CS were used as the hydrogel matrix.Under the action of the initiator,acrylic acid was grafted into the side chains of BC and CS through redox polymerization to prepare p H-responsive hydrogels.TGA,FTIR,SEM and material testing machines were used to study the thermodynamic properties,chemical structure,morphological characteristics and mechanical properties of the hydrogels.The SEM results showed that all hydrogels showed a porous structure and with the increase of the addition of bacterial cellulose,the pores of the hydrogels gradually collapsed and the regularity of the pores gradually deteriorated.FTIR showed that covalent bonds were formed between the various monomers.The maximum compressive strength of the hydrogel can reach 330.9 KPa,and the maximum tensile strength can reach 21.3 KPa.The swelling behavior of hydrogels in buffer solutions with different p H values showed that the swelling of hydrogels was p H-dependent.The minimum equilibrium swelling rate of the series of gels obtained with different BC/CS ratios all appeared at p H3.5-p H5 and the equilibrium swelling rate increased significantly at lower or higher p H values.The results of in vitro simulation experiments showed that the cumulative release of the loaded drug-naproxen in simulated gastric juice was less than that in simulated intestinal juice.It could achieve directional release in the intestinal tract and the sustained release time exceeded24 hours.It had great potential in the sustained release of intestinal drugs.