Preparation And Properties Of Multifunctional Composite Hydrogel-based Wound Dressings

The skin plays a vital role in protecting the body from external stimuli,but it is vulnerable to outside exposure.After being subjected to injury,the skin will lose its protective functions,ultimately leading to the formation of wounds.At this time,a medical dressing is usually required to cover the wound to speed up the healing process.Due to the low price and easy access,dry sterile gauze is currently the most commonly used wound dressing.However,it will adhere to the wound after absorbing wound exudate,causing damage to the wound when changing the dressing.Since the concept of wet healing was proposed by George Winter in the 1970s,the theory of wet wound healing has been accepted and attracted many people's attention.Nowadays,many wet wound dressings have been developed,such as alginate,electrospinning membranes,hydrocolloids,transparent dressings and hydrogels,etc.Among them,hydrogels have attracted the interest of many researchers due to their good hydrophilicity,biocompatibility,and 3D porous structure like extracellular matrix.However,simple hydrogel dressings can only play the role of physical isolation and create a moist environment,which cannot meet the increasing clinical requirements for wound dressings.With the improvement of basic research,developing multifunctional materials to meet various needs of wound repair has become the mainstream trend in the design of wound dressings,and hydrogel-based wound dressings are no exception.In addition,according to different skin wound conditions,targeted wound repair materials should be used to better promote wound healing.Therefore,in order to meet the clinical needs and in response to the possible existence of skin wounds,in this dissertation,multifunctional composite hydrogel-based wound dressings were designed and prepared to promote wound repair.The main research contents are as follows:1.In the first research part of the dissertation,an electrospinning fiber membrane-hydrogel bi-layered composite surgical dressing imitating skin structure was biomimetic designed and prepared for clean wounds with large area.The upper layer was an electrospinning fiber membrane with ideal tensile mechanical properties and dense structure.It can avoid microbial permeability,prevent infection,and prevent external stimuli through covering the wound.The lower layer was a porous hydrogel,which has sufficient porosity,wettability and biological properties to support cell adhesion,migration and proliferation.The bi-layered structure is similar to the epidermis and dermis of natural skin,which can weaken bacterial infiltration while avoiding wound dehydration and exudate accumulation,and has a good application prospect in promoting wound healing.The results showed that the diameter of the upper membrane fibers was similar to that of the extracellular matrix fibers,which is beneficial to the adhesion and proliferation of keratinocytes in the epidermis.The pore size of the lower hydrogel was greater than 100?m,which is also favored for the proliferation and migration of fibroblasts in the dermis.At the same time,relying on the hydrogel,the bi-layered composite surgical dressing also possessed good swelling properties(which are closely related to the ability of absorbing wound exudate),good adhesion(which can help the material to seal the wound from external stimuli),and better hemostatic ability than the commercial hemostatic sponge.In vitro cell co-culture experiments demonstrated that Ha Ca T and ESF could grow well in the membrane and hydrogel of the material.In the in vivo wound healing test,the wounds treated with the bi-layered composite surgical dressing showed faster healing rate than other groups.2.In the second research part of the dissertation,from the perspective of effective coverage of irregular wounds and anti-infection,an injectable double-effect antibacterial composite hydrogel doped with polydopamine modified silver nanoparticles was designed and prepared for the irregular infected wounds.Polydopamine modified silver nanoparticles in the hydrogel not only paly a role of traditional antibacterial agent,but also a photothermal antibacterial agent.It can help hydrogel to kill most bacteria through photothermal therapy assisted by near-infrared light in the short term,and inhibit bacterial reproduction through sustaining release of silver nanoparticles in the long term,thus antibacterial activity of hydrogel surgical dressings improved.The base materials of the hydrogel continued using gelatin and sodium alginate,inspired by mussels,the catechol groups were grafted onto the gelatin.Then the double dynamic bond-crosslinked hydrogel was fabricated through catechol-Fe coordinate bond and Schiff base(between aldehyde groups on alginate di-aldehyde and amino groups on catechol-modified gelatin).And polydopamine-modified silver nanoparticles were also incorporated into the hydrogel.Double dynamic bonds endowed the hydrogel with injectability;the addition of catechol groups improved the adhesive strength of the hydrogel;the addition of the antibacterial agent polydopamine-modified silver nanoparticles not only endowed the hydrogel with traditional antibacterial activity,but also introduced the performance of photothermal sterilization.In addition,the hydrogel also had good biocompatibility and better in vivo hemostatic property than the commercial hemostatic sponge.In the in vivo infected wound healing experiment,with the assistance of near-infrared light,this hydrogel treated wound showed better healing effect,and the wound tissue had more new blood vessels and hair follicles.3.In the third research part of the dissertation,from the perspective of further improving the mechanical properties of hydrogel surgical dressings,an adhesive hemostatic antibacterial composite hydrogel was designed and prepared for the joint infected wounds.The preparation process of hydrogel can be divided into two steps:enzymic catalysis crosslinking and soaking in tannic acid.Enzyme catalyzed crosslinking avoids the introduction of other crosslinking agents.After soaking in tannic acid,the mechanical properties,adhesiveness and hemostatic performance of the hydrogel greatly improved,avoiding the multiple preparation steps that may be needed to enhance the multifunctional properties of hydrogel wound dressings.Tyramine-grafted carboxymethyl cellulose(CMC-Ty)was first mixed with two-dimensional few-layer MXene(Ti₃C₂T_x)which was prepared by acid etching.And a hydrogel named as CMC-Ty/MXene was obtained through enzymatic crosslinking.Then CMC-Ty/MXene was soaked in tannic acid aqueous solution for 12 h,the obtained hydrogel was named CMC-Ty/MXene+TA.Tannic acid is a natural plant-derived polyphenolic compound with a large number of catechol/triphenol groups.And it also possesses a variety of binding abilities which help it to be able to crosslink with macromolecules through various interactions such as ionic bonds,hydrogen bonds and hydrophobic interactions.The results showed that the tensile strength of CMC-Ty/MXene+TA reached 250 k Pa,the elongation at break was also more than 250%,and the adhesive strength was above25 k Pa,which were better than the results of the above two prepared wound dressings.When the CMC-Ty/MXene+TA hydrogel was attached to the human elbow,the experimenter can bend the arm freely,the hydrogel was adhered to the arm tightly without falling or breakage,indicating that CMC-Ty/MXene+TA hydrogel has the potential to be used as a joint wound dressing.And CMC-Ty/MXene+TA hydrogel also has good in vitro and in vivo hemostatic properties.In addition,the hydrogel also showed good bactericidal effect against E.coli and S.aureus,which is not only due to the photothermal sterilization properties of MXene,but also related to the antibacterial activity of tannic acid.Finally,in the S.aureus infected skin wound healing test,with the assistance of near-infrared light,CMC-Ty/MXene+TA hydrogel can kill bacteria,promote epidermal regeneration,down-regulate the expression of tumor necrosis factor-?and accelerate angiogenesis,showing good wound treatment effect.To sum up,in this dissertation,an electrospinning fiber membrane-hydrogel bi-layered composite surgical dressing was biomimetic designed to simulate the skin tissue structure for clean wounds with large area;an injectable antibacterial composite hydrogel doped with polydopamine-modified silver nanoparticles was designed and prepared for irregularly shaped infected wounds;a photothermal antibacterial hydrogel doped with 2D sheet MXene was designed,and the mechanical properties and adhesion of the hydrogel was improved by soaking in tannic acid.The physicochemical properties,in vitro and in vivo biocompatibility and the ability of promoting wound healing of the materials were evaluated,in order to provide new ideas for the development and application of multifunctional composite hydrogel-based wound dressings.