| Uncontrollable hemorrhage is one of the main causes of military and civilian trauma deaths.It is particularly important for saving the wounded and lives to achieve rapid and effective pre hospital hemostasis.Due to large specific surface area,high porosity and rich alcohol hydroxyl structure,Mesoporous silica has good coagulation effect.However,mesoporous silica also has some problems,such as weak tissue adhesion,poor sealing and no antibacterial,which is difficult to stimulate multiple coagulation factors of complex coagulation pathways simultaneously.In this study,to achieve multi-channel hemostasis from intrinsic and extrinsic pathways,synergistic effect of hydrophilicity and hydrophobicity,and anisotropic hemostatic and antibacterial effect,a series of organic-inorganic composite hemostatic dressings were prepared by compounding mesoporous silica with natural products with tissue adhesion and hydrophobic plugging effects,supplemented by amino and silver nanoparticles.Its physicochemical properties,hemostatic performance,antibacterial activity and biosafety were characterized,and its hemostatic and antibacterial mechanism was systematically discussed.The main research contents and conclusions are as follows:（1）MSN@CS-HCA were prepared by chitosan and hydrocaffeic acid surface modification of mesoporous silica nanoparticles,to improve its tissue adhesion.MSN@CS-HCA with core-shell structure had good monodispersity,rich pore structure,large specific surface area,high negative charge and good thermal stability.In the hemostatic model of SD rat’s liver and femoral artery,the hemostatic time of MSN@CS-HCA was shortened by approximately 43%and 60%compared with MSN,and was about 23%and 16%shorter than that of MSN@CS.The good hemostatic ability of MSN@CS-HCA was mainly due to the synergistic effect of erythrocyte aggregation and adhesion,negative charge stimulation,and the formation of three-dimensional network structure.MSN@CS-HCA was non-cytotoxic and did not cause damage to the tissues around the wound.MSN@CS-HCA is expected to become a safe and rapid local hemostatic dressing.（2）The Janus particles（Ca-TA-MSN@Ag）with silver nanoparticles（Ag NPs）at one end,and MSN cross-linked and coated by calcium ions and tannic acid at the other end,were prepared to promote exogenous hemostasis.Ca-TA-MSN@Ag had negatively charged surface and high specific surface area(510.62 m2·g-1).Compared with MSN,the in vivo hemostatic time of Ca-TA-MSN@Ag was shortened by nearly 50%.Ca-TA-MSN@Ag could achieve rapid coagulation by the synergistic effect of multiple hemostatic mechanisms,including activating intrinsic and extrinsic pathways in the clotting cascade,aggregating erythrocytes,and tissue adhesion.The antibacterial rate of Ca-TA-MSN@Ag against E.coli and S.aureus reached nearly 99%,and it had good hemocompatibility and cytocompatibility.The good hemostatic and antibacterial performance of Ca-TA-MSN@Ag make it promising to be an efficient and safe hemostatic and antibacterial wound dressing.（3）In order to study the blood blocking effect of the interface-directed self-assembled hydrophobic layer,catechol structure with long alkane chain was introduced to prepare urushiol-functionalized mesoporous silica nanoparticles（MSN@U）hemostatic dressing.MSN@U possessed rich mesoporous structure,high negative charge（-40.85 mV）,and could orientately self-assemble to form hydrophilic/lipophilic Janus films at the water/air and water/oil interfaces.The porosity,sealing property of directional self-assembled films,the activation of negative charges,and the adhesion of the catechol structure enabled MSN@U to have rapid coagulation effect.In the hemostatic model of SD rat’s liver and femoral artery,MSN@U had the best hemostatic ability,and its hemostatic time was shortened from 54 s and 77 s of MSN to 22 s and 34 s,respectively.The good biosafety of MSN@U makes it promising to be used as an excellent hemostatic dressing in clinical practice.（4）In the anisotropic cardanol-coated MSN-silver（C-MSN@Ag）Janus hemostatic dressing,cardanol was not as sensitizing as urushiol.The click-cardanol-coated MSN reaction had the advantages of simple operation,no free radical initiator,mild reaction conditions,good selectivity,high product yield,and less side reactions.The hydrophobic alkyl and hydrophilic phenolic hydroxyl structures of cardanol endowed C-MSN@Ag with good hemostatic performance,and the hemostatic time of C-MSN@Ag was about 40%shorter than that of both MSN and MSN@Ag in SD rat’s liver trauma model.Besides,C-MSN@Ag could form the three-dimensional network structure with fibrin,which increased the mechanical strength of blood clots.In addition,C-MSN@Ag showed excellent antibacterial properties and good cytocompatibility.This anisotropic material can provide inspiration for the spatial structure design of multifunctional wound dressings,and supply theoretical and experimental references for Janus hemostatic materials with clinical application potential.（5）Inspired by the structure of skin,a chitosan（CS）/acacia gum（AG）/quaternized mesoporous bioglass（QMBG）injectable cryogel sponge（OCAQ）with hydrophilic/hydrophobic Janus structure was prepared by simple blending,chemical cross-linking,and surface modification.OCAQ possessed interconnected macroporous structure,stable mechanical properties,rapid water/blood-triggered shape recovery（～2 s）,high water absorption ratios（～5417%）,and large volumetric expansion ratios.The introduction of AG greatly improved the toughness and shortened shape recovery time of OCAQ with 78%shorter than CS sponge.Besides,the incorporation of QMBG significantly induced and promoted the adhesion and activation of red blood cells and platelets.More importantly,the asymmetric hydrophobic surface modification of octadecanal endowed OCAQ with outstanding antiblood and antibacterial permeability,effectively preventing blood outflow and the invasion of bacteria to the wound.These synergistic effects enabled OCAQ to have the best hemostatic effect.In SD rat’s liver injury model,the blood loss of OCAQ was reduced from 0.49 g of pure CS sponge to 0.14 g.Moreover,OCAQ exhibited favorable good biosafety and antibacterial activity.OCAQ Janus multifunctional dressing used in the deep and narrow non-compressible wounds combines the organic-inorganic and hydrophilic-hydrophobic structures and possesses the intrinsic-extrinsic hemostatic pathway and the hemostatic-antibacterial property.It is the most potential material for urgent and clinical application. |
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