Fabrication And Properties Investigation Of Hemostatic Calcium Alginate Microsphere Dressings For Antibacterial And Wound Healing

Wound dressings have proven to be effective in treating tissue bleeding,breakage,and infection.Powdered dressings in microsphere formulations offer a versatile solution,as they are not limited by wound size,shape,or location,making them suitable for emergency treatment of irregular or deep wounds.By utilizing the natural polysaccharide polymer sodium alginate,microsphere dressings with excellent hemostatic properties can be created using reverse emulsion and Ca²⁺cross-linking methods.These calcium alginate microspheres（CA）have the ability to rapidly absorb water from the blood and release Ca²⁺,thereby promoting blood clotting and achieving hemostasis efficiently.While CA powder dressings are effective for managing simple bleeding wounds,they may not fully address the complexities of more severe injuries.In order to meet the requirements of wound healing,a dressing with hemostatic functionality alone is insufficient.Therefore,the aim of this research is to develop multifunctional CA wound dressings capable of addressing a range of wound types,including rapid wound hemostasis,bacterial inhibition,inflammation elimination,and wound healing.This study focuses on four main aspects:Investigating methods to optimize the hemostatic properties of CA dressings,ensuring they can effectively control bleeding in various wound scenarios;Exploring techniques to incorporate antibacterial agents into CA dressings,enabling them to prevent or combat wound infections;Developing strategies to incorporate anti-inflammatory components into CA dressings,facilitating the reduction of inflammation in wounds;Researching approaches to enhance the wound healing process by incorporating materials or factors that can stimulate tissue regeneration and accelerate the formation of new skin.By addressing these four aspects,the goal is to create advanced CA wound dressings that possess the necessary attributes to address a wide range of wounds effectively.The study mainly includes the following aspects:（1）The hemostatic properties and the ability to promote wound healing of calcium alginate/silk fibroin peptide（SP）composite microspheres（CA/SP）prepared by reverse emulsion and ionic cross-linking after immobilization of thrombin（Th）were studied.The results demonstrate that the addition of SP has several beneficial effects on the microspheres.Firstly,it enhances the swelling performance and porosity of the microspheres by reducing the density of calcium alginate.This improved swelling capacity allows for better absorption of wound exudate.Additionally,the incorporation of SP improves the stability of thrombin through hydrogen bonding interactions,thus preserving its enzymatic activity.Furthermore,the inclusion of SP was found to have a positive impact on fibroblast viability,which plays a crucial role in wound healing.These suggest that CA/SP@Th has the potential to be a multifunctional dressing for wound hemostasis and healing.（2）Multi-pathway composite coagulation microsphere（m CSB,calcium alginate/silk fibroin peptide/Bletilla striata polysaccharide）was prepared by reverse emulsion and ionic crosslinking,and its coagulation mechanism was studied.These microspheres have platelet agglutination function and can achieve synergistic hemostasis of multiple coagulation pathways,including platelet activation,blood cell agglutination,and release of Ca²⁺.Among them,platelet aggregation attributable to the stimulation of Bletilla striata polysaccharide（BSP）.Furthermore,the microspheres have shown good loading and slow releasing properties of the water-soluble drug tannic acid（TA）.The m CSB@TA exhibits long-lasting antibacterial effects and can also inhibit wound inflammation,which accelerates wound healing.In summary,the microspheres-m CSB have potential in achieving synergistic hemostasis and delivering water-soluble drugs for antibacterial and anti-inflammatory effects,ultimately improving wound healing.（3）Self-assembly and in-situ coordination methods were utilized to create CA/SP@TA/Fe（tannic acid/Fe）microspheres,which possess photothermal antibacterial characteristics.The hemostatic mechanism and antibacterial properties of these microspheres were also investigated.The study demonstrated that CA/SP@TA/Fe could effectively inhibit the growth of S.aureus and P.aeruginosa by more than 99%when exposed to NIR light.Further investigation revealed that the hemostatic mechanism of CA/SP@TA/Fe was due to the electrolyte effect of TA/Fe,which facilitated the agglomeration and sinking of blood in a colloidal state,thereby enhancing blood coagulation.In addition,CA/SP@TA/Fe was found to inhibit wound inflammation and promote fibroblast proliferation under NIR light,which in turn enhanced the wound healing rate.Overall,these findings suggest that CA/SP@TA/Fe has promising potential as a multi-purpose wound dressing.（4）Microspheres designated as CA/SP@Ag Ns（Ag nano particles,Ag Ns）were produced using an in-situ reduction technique,enabling them to have an Ag⁺slow-release capacity.The impacts of the structure of microspheres on wound hemostasis,bacterial inhibition,and healing properties were investigated.The migration studies of Ag Ns demonstrated that TA/Fe had good immobilization ability for Ag Ns.The release kinetics of Ag⁺from CA/SP@Ag Ns was studied,and it was found that the mechanism of Ag⁺release involved solution diffusion and spheroid dissolution.Based on the strong antibacterial properties of Ag⁺,low doses of CA/SP@Ag Ns were able to completely inhibit the growth and reproduction of S.aureus and P.aeruginosa.The in vitro and in vivo biocompatibility studies showed that the microsphere dressing with the function of slow releasing Ag⁺could significantly reduce the toxicity of heavy metal ions to organisms,making it a safe and effective bacteriostatic dressing.In summary,this study presents a comprehensive approach involving the construction of composite microspheres,the incorporation of active ingredients,and the exploration of advanced strategies for wound treatment.The findings not only demonstrate the potential of the developed dressing but also lay the groundwork for further advancements in the field of wound healing.