Homogeneous Synthesis,Properties Of Hydroxybutyl Chitosans And Their Applications In Wound Healing

Nowadays,the ocean as a treasure trove of human development has attracted widespread attention from scientists.Chitin is the most abundant biomass resource in the ocean,and it is also the natural polymer second only to cellulose in nature.Its deacetylated product-chitosan(CS)is not only easy to be physically and chemically modified,but also can be processed into various forms.It has excellent biocompatibility,biodegradability,antibacterial property,tissue adhesion and other biological activities.Derivatization is often used to improve the properties of CS and endow it new structures and functions.In this work,CS was used as raw material to homogeneous synthesis of hydroxybutyl chitosan(HBCS)under mild conditions in alkali/urea aqueous solutions.The structures,solution properties and biological activities of the products were investigated.Moreover,its application for wound dressings was also studied.The novel creations of this work are as follows: 1)A series of HBCS were homogeneously synthesized in the alkali/urea aqueous solutions for the first time.The structures,solution properties and phase transition behavior were studied in depth;2)The biological activities of HBCS such as antioxidative and antibacterial activities,biocompatibility,hemocompatibility were investigated.And the wound dressing of HBCS was proved to promote wound healing.The main contents and conclusions in this thesis are divided into the following parts.HBCSs with a degree of substitution(DS)ranging from 0.38 to 1.54 were homogeneously synthesized in KOH/LiOH/urea aqueous solutions under ambient conditions.The amino group at C2 and the hydroxyl groups at C3 and C6 of CS all participated in the reaction,while substitution mainly occurred at the hydroxyl groups at the C6 position.The aqueous solution of HBCS with a DS above 1.25 had unique thermosensitivity,which exhibited a sol-precipitation behavior when heated to a critical temperature.While the HBCS obtained in a heterogeneous system underwent a sol-gel transition.In vitro cytotoxicity assay demonstrated that HBCSs were not-cytotoxic and could even promote the proliferation of normal cells.Antibacterial assessments revealed that HBCSs partially retained the antibacterial activity of CS,and its antibacterial ability decreased with increasing DS.Antioxidation experiments showed that HBCSs have certain antioxidative activities.The results indicated that homogeneously-synthesized HBCS possess potential applications in the fields of food,medicine and biomedical industrials.High-molecular-weight CS was used as raw material to prepare HBCS with DS of 0.41~1.38 in KOH/LiOH/urea aqueous solutions.The introduction of hydroxybutyl groups allowed the self-assembly of HBCS to form micelles in water,and the particle size of the micelles decreased with increasing DS.Three-dimensional porous sponges were fabricated by vacuum freeze-drying of HBCS aqueous solutions.The HBCS dressings displayed enhance cell proliferation and viability in NHDF cells in vitro and a certain antibacterial ability.Hemolysis and coagulation experiments demonstrated that HBCS with a higher DS exhibited better blood compatibility and lower BCI values than the other sponges.In vivo wound-healing evaluations in rats showed that HBCS sponges with a higher DS could promote the proliferation of fibroblasts and reduce wound infection,which can significantly shorten the time of wound healing.Therefore,HBCS sponges have potential clinical applications for promoting wound healing.The basic research results mentioned above proved that the alkali/urea aqueous solution was a suitable and stable solvent and reaction medium for the homogeneous synthesis of HBCSs,which provides a new method for the preparation of CS derivatives.Meanwhile,this work clarifies the relationships among the structures,properties and applications of HBCSs,providing important scientific evidences for the construction of novel CS-based functional materials.