Preparation Of Chitosan-based Composite Hydrogel As Wound Dressing For Skin Healing

The problem of skin damage has been plaguing humans.Skin damage can cause pathological changes,such as metabolic disorders,immune system and electrolyte imbalance,and even life-threatening.To accelerate the healing of the wound and reduce the incidence of lesions,the skin wound dressing is covered as a temporary substitute for the skin to protect the wound site and accelerate wound repair.However,traditional dressings represented by gauze,cotton balls,cotton pads,etc.have many defects,such as passive protection,slow repair rate and easy secondary trauma,so the demand for novel efficient dressings is increasing.Recently,research on hydrogel dressings for wound repair has received extensive attention.Hydrogel dressings can impart a moist environment to the wound and have the function of highly effective drug retention and sustained release drugs,which are beneficial for wound healing.In addition,hydrogel dressings can be imparted with specific functional properties,which make hydrogel dressings more targeted for different types of wounds.For example,the properties of pH sensitive,glucose responsive,antimicrobial,and high adhesion can be imparted to the hydrogel dressings.In this paper,functional hydrogel dressings were prepared on the basis of chitosan to achieve targeted repair of different types of wounds.The specific research is divided into three parts as follows:1.Here,a rapidly gelled pH-responsive hydrogel was prepared through the Schiff's base byusing oxidized hyaluronic acid(OHA)and succinyl chitosan(SCS).Glucose stimuli-responsive microspheres were self-assembled by poly(ethylene glycol)-b-poly[3-acrylamidophenylboronic acid-co-styrene](PEG-b-P(PBA-co-St),constructed by PEG2000,3-acrylamidophenylboronic acid and styrene.Insulin-loaded microspheres(ILM)and epidermal growth factor(EGF)can be embedded in hydrogels during the in-situ cross-linking of SCS and OHA to obtain composite hydrogel dressings for skin damage repair in hyperglycemic people.The gel time of the hydrogels were judged by detecting the change in viscosity and modulus during the formation of the hydrogel;the cytotoxicity of the hydrogel dressings were evaluated by detecting the cell viability of the hydrogel and the feasibility as a cell carrier and cell scaffold;The composite hydrogel dressing was used to repair the trauma of diabetic SD rats to evaluate the feasibility of biological experiments.The granulation tissue formation and repair situation at the wound was observed by hematoxylin-eosin(H&E)staining of the skin slices at the wound site.The experimental results show that the composite hydrogel not only promotes wound repair in SD rat with hyperglycemia,but also stabilizes blood glucose concentration.2.A zinc-doped bioactive glass(ZBG)/succinyl chitosan(SCS)/oxidized alginic acid(OAL)composite hydrogel dressing with pH sensitivity and injectability was prepared by Schiff's base reaction.The alino groups from SCS and Zn2+ ions released from ZBG made the excellent antibacterial properties to composite hydrogels that confirmed by the antibacterial tests in vitro.The Si and Ca2+ions can stimulate the fibroblast cells to develop essential growth factors(EGFs)for angiogenesis and wound closure processes.In addition,the epidermal growth factors embedded into the hydrogels can significantly improve the cell proliferation and tissue remodeling in the wound bed.The antibacterial performance and antibacterial efficiency of the composite hydrogel were evaluated by bacteriostatic characterization.The composite hydrogel dressing was used to repair the skin wound on the back of SD rats,then,the wound sections were stained by H&E and MT staining to analyze the proliferation of fibroblasts,the formation of granulation tissue,the formation of blood vessels and glands,and the deposition of collagen and myofibril.The inflammatory response of SD rats was detected by labeling the interleukin(IL-6)content at the wound,and the angiogenesis of SD rats was detected by CD-31 and ?-SMA staining methods.The experimental results show that the composite hydrogel dressing has excellent antibacterial properties,can accelerate the healing of wounds,reduce the formation of inflammatory reaction,and promote the regeneration of granulation tissue and blood vessels and glands.3.Regenerated silk fibroin(RSF)was obtained by degumming silkworm cocoons,followed by the operation of dissoluting,dialysis and lyophilization.In addition,?-polylysine-modified chitosan(PCS)with excellent antibacterial property was prepared by grafting ?-polylysine onto chitosan through amidation reaction.RSFs were physically complexed by Ca2+ ions and chemically crosslinked with PCSs to form antibacterial composite hydrogels with excellent adhesion property.The antibacterial performance and antibacterial efficiency of the hydrogel were evaluated by bacteriostatic characterization against E.coli and S.aureus.To evaluate the adhesion of hydrogels,the adherent stress of the hydrogel was characterized for different materials.The results showed that the hydrogel has excellent adhesion properties to ceramics,glass,wood,plastics,iron and porcine skin.The adhesion property of hydrogel is depended on its moisture content.The shear adhesive strength of the hydrogel-bonded skin exceeds 75 kPa when the swelling ratio of hydrogel is 100 wt%,which makes the hydrogel potentially useful as a suture adhesive.The composite hydrogel dressings with EGF were used as the application of wound healing on SD rats in vivo.Because of their excellent adherent properties and antibacterial abilities,the as-prepared composite hydrogels exhibited a excellent wound healing properties in comparison with control groups.These results indicated that the adherent hydrogel can fully adhere,fix and heal the wound by in vivo experiments.Researches and tests have shown that the composite hydrogel dressings have the potential to adhere and repair wounds,and also have a potential value in the field of wound adhesive.