Study On Preparation And Performance Of GelMA-BSP Hydrogel For Promoting Wound Healing

Diabetes mellitus is a common chronic metabolic disease.Due to the influence of environmental and genetic factors,the prevalence of diabetes mellitus is increasing rapidly in the world,which has a serious impact on thousands of people worldwide.Diabetes can cause a series of complications that pose a threat to the health of the patient.Diabetic foot ulcers,in particular,are chronic wounds caused by poor wound healing.Diabetic wound is chronically over-inflamed,susceptible to recurrent bacterial infections and impaired vascularization,which leads to the wound is difficult to heal.New dressings with added antibiotics,anti-inflammatory drugs and growth factors are currently used for diabetic wounds with certain therapeutic effects,but some of them have disadvantages such as easy inactivation,resistance and toxic side effects.Therefore,the development of non-antibiotic dressings that inhibit wound infection and promote cell adhesion,proliferation and vascular regeneration is urgently needed for the treatment of diabetic wounds.The high water content of hydrogels is conducive to maintaining a moist wound healing environment and relieving wound discomfort.In addition,its structure is similar to natural extracellular matrix（ECM）,which can provide a suitable environment for cell proliferation.Therefore,it is a promising dosage form for wound dressings.Gelatin has excellent biocompatibility,cell adhesion and degradability,but gelatin-based gels have poor mechanical properties,the lack of hermal stability,and can not be formed at normal physiological temperature,which limits their use in the field of biological materials.Modified gelatin（GelMA）retains the good cellular correspondence of gelatin and has properties of bonding and cross-linking which can be prepared to obtain thermally stable hydrogels,but the mechanical properties are poor.Generally,the mechanical properties can be enhanced by adding nano particles or blending with other materials.Bletilla striata polysaccharide（BSP）is a natural viscous polysaccharide,which is the main active ingredient of traditional Chinese medicine Bletilla striata,with the advantages of biocompatibility,cell proliferation,immune modulation and wound healing.Moreover,BSP contains a large number of hydroxyl groups that can easily form intermolecular hydrogen bonds with hydrophilic groups such as-OH and-NH₂.In this study,BSP was added to the pure GelMA hydrogel（Gel）to enhance the mechanical properties of Gelby intermolecular hydrogen bonding and obtain semi-interpenetrating gel（GB）.However,GB hydrogel lacks antimicrobial activity,by adding tannic acid and iron ion(TA-Fe³⁺)complexes as near-infrared（NIR）photothermal converters to obtain the material of non-antibiotic,broad-spectrum photothermal antibacterial activity,which is beneficial to the gel application in chronic wounds prone to infection.Therefore,in this study,gelatin was modified with methacrylic anhydride（MA）to obtain GelMA with medium degree of substitution,BSP was prepared by aqueous extraction and alcoholic precipitation,and pure GelMA hydrogels（Gel）,semi-interpenetrating gels（GB）with the addition of BSP,and a series of composite hydrogels（GBTF）with the introduction of TA-Fe³⁺NIR trigger materials were prepared by free radical polymerization.The morphological structure,mechanical properties,swelling properties,NIR photothermal effect,rheological behavior,antioxidant activity,antibacterial properties,cytotoxicity,cell proliferation and in vivo promotion of diabetic wound healing effects of the different component hydrogels were investigated.The results showed that all the hydrogels have a three-dimensional porous structure and good swelling properties,which could absorb wound exudate and facilitate gas exchange at the wound.Compared with Gel,GB hydrogel has a smaller pore size and a slightly lower swelling property.Due to BSP can enhance the mechanical properties of the Gelhydrogel.The NIR photothermal effect in the composite hydrogel GBTF system was enhanced with the increasing concentration of TA-Fe³⁺complex.When the concentration of TA,Fe³⁺was 1000,500μg/mL respectively,the hydrogel GBTF（10）has good photothermal effect,antibacterial and antioxidant activities.And MTT assay and live/dead cell staining showed that the hydrogel is non-cytotoxic and can promote cell proliferation.In diabetic rats with full-thickness skin damage model,hydrogel GBTF（10）can promote wound healing under NIR irradiation.In conclusion,the prepared composite hydrogel GBTF（10）has good mechanical properties,swelling ability,antioxidant property,cytocompatibility,and can promote diabetic wound healing through photothermal antibacterial,which confers non-antibiotic to the dressing,and provides new ideas and new strategies for clinical treatment of diabetic wounds.