Preparation And Characterization Of Degradable Mesoporous Silica Xerogels For Hemorrhage Control And Bone Repair

Combat trauma care is always the top priority of the development of military medical sciences, especially for the modern warfare and major emergencies. High-performance biomaterials and products therefore become very important for the treatment of large-scale trauma and war injuries. Blood loss and bone damage are not only the major causes in war injuries, but the problems in emergency and essential surgical care. In modern battlefield, with the increasing injuries caused by burn and explosion, the wounds are more and more different to heal owning to the serve uncontrolled blood loss and infection. So the safe, rapid and effective approatch for bleeding control and wound healing are very important to the reduction of rate of death and infection. It is essential to develop novel hemostatic materials with properties of good biocompatibility and biodegradability used for both civilian and military. Although a wide variety of artificial biomaterials for bone defect have been widely developed currently, their bioactivity, biocompatibility, biodegradability and mechanical properties are still less than optimal, which limits their applications. It is therefore imperative to develop new biomaterials for bone regeneration.Mesoporous materials, with well ordered mesopores, large surface areas and porosity, tunable skeletal structure and inner surface, have exhibited wild applications in many fields since the past decades. The current study, based on the silica-based mesoporous materials with porous architecture as well as procoagulation factors, aimed to develop safe and effective local haemostatic materials. Meanwhile, we also fabricated a bioactive and biodegradable bone graft substitute combined with osteogenic factors and investigated the mechanism of their bone regeneration and degradation.We prepared large surface areas and well ordered mesoporous silicas doped with calcium and silver (AgCaMSS) by using TEOS as precursor via modified sol-gel and ionic exchange methods. In vitro study demonstrated that the materials possess good degradable property with a peak value of silver ions concentration at 24h. The coagulation assay in vitro showed that the materials could achieve effective hemostasis through initiating the intrinsic pathway of coagulation and thus shorten the aPTT value; the agent could significantly promote the platelet adhesion and stimulate the platelet spreading on the surface of materials. The animal model indicated that the AgCaMSS agent produce rapid and effective hemorrhage control in the injuries of rabbit ear vein, liver and femoral artery; they also provided high efficacy of bleeding control in severe femoral artery injury on large mammals with low heat effect. The antibacterial tests showed that the materials had great antibacterial properties against gram-positive and gram-negative bacteria with sustained effects. The materials were non-cytotoxic and biocompatible. The complete degradation occurred at 3 months although the implantation may cause limited inflammatory response in early period.We prepared a composite hemostatic agent (CSSX) by using mesoporous silicas as core and chitosan with hemostatic activity as shell, via phase inverse and molecular imprinting technique. The coagulation assay in vitro showed that the CSSX agents could significantly shorten the aPTT value; and achieve effective hemostasis through electrostatic effect of surface negative charge and positive charge on the silica core and macroporous chitosan shell, respectively, which is a mutil-mechanism. The in vivo test demonstrated that the CSSX agent produce rapid and effective hemorrhage control in the injuries of rabbit ear vein, liver, spleen and femoral artery. The agents were safe to the surrounding tissue without any necrosis and infection. They also promoted tissue growth and shorten the healing period without scars. The materials had no effects on the cell morphology, growth and proliferation and had good biocompatibility without hemolysis, skin irritation and sensitization.By using different surfactant and hydrothermal treatment, we developed a serial of mesoporous calcium/magnesium containing silicas with different pore sizes. Then we obtained a complex rhBMP-2/CMMS materials with osteogenic properties by loading recombinant human bone morphogenetic protein-2 (rhBMP-2). The assay showed that the materials degraded well in vitro with excellent rhBMP-2 protein release profiles. They were proved to be bioactive and had no effects on cell proliferation and differentiation and alkaline phosphatase activity. Ectopic bone formation assay indicated that the materials had significant ability to induce bone formation. The in vivo experiments showed that the new bone formation and material degradation in defect sites increased with time, suggesting that the materials can significantly promote the process of bone regeneration and are supposed to be promising biomaterials for bone repair.