Hemostatic Materials Based On Quaternized Starch And Tannic Acid Complex

Uncontrollable massive bleeding is an important cause of casualties,but the commonly used hemostatic materials are limited by their inadequate performance.Therefore,it is of great improtance to develop high-peformance and safe hemostatic materials.Starch and other polysaccharides possess the advantages of wide material sources and high safety.As a natural polyphenol,tannic acid(TA)has several favorable features for biomedical applications,such as antioxidative and antibacterial funtions.Both of them have been widely used in the field of biomedical materials/medical devices.Based on above,this paper intends to prepare medical(procoagulant)coatings/hemostatic sponges(based on cationic modified starch/TA complex)and investigate their hemostatic applications.Procoagulant coatings can improve the performance of hemostatic materials/devices to meet the increasing needs in clinical therapy,which normally donnot chang their application scenarios.In Chapter 2,quaternized starch(QS)was firstly prepared by grafting epoxy quaternary ammonium salt on amylopectin.Then,QS was mixed/assembled with TA in aqueous solution to prepare the stock solution of QS/TA(complex)coating.Five QS/TA-coated gauze(G-QTs)were prepared by soaking medical gauze(G)in stock solutions with different QS/TA feed ratios.In vitro results showed that only G-QT-9/1with optimal coating structure(QS/TA ratio of 9:1)possessed better hemostatic property than G.The underlying mechanism was revealed that the optimal coating improved the platelet adhesion ability of G-QT-9/1 and did not disturb the corresponding internal/external coagulation pathway.The rat femoral-artery-injury model further confirmed the better hemostatic performance of G-QT-9/1 than G.Meanwhile,five G-QTs displayed negligible hemolysis rate and their leachates showed no procoagulant effect,which demonstrated the high safety of QS/TA coatings.Finally,QS/TA coating was applied to the surface modification of starch microsphere & medical polyvinyl alcohol sponge,which indicated that QS/TA coating can act as a universal procoagulant coating for polymeric substrate/medical devices.Although the hemostatic performance of G was improved by based on QS/TA coating,there still exist some shortcomings,i.e.,nondegradable G restricts the favorable degradability of such coating and therefore G-QS/TA is not suitable for local packing/long-term implantation to achieve hemostasis.In Chapter 3,hydroxypropyl cellulose(HPC)was introduced into QS/TA solutions of three ratios and further freeze-dried to prepare ternary composite sponges(HQTs).The optimial HQT10(QS/TA ratio of 10:1)possessed better hemostatic property than the other two HQTs,which was also better than the binary composite sponges prepared by QS/TA solution.Two rat-hemorrhage models(femoral-artery-injury and partial resection of brain tissue)further demonstrated the better hemostatic performance of HQT10 than medical gelatin sponge and Surgicel dressing,whilst HQT10 also showed good in vivo degradation and histocompatibility after the implantation at brain-defect sites.The procoagulant mechanism of HQT10 was revealed that the procoagulant effect does not depend on the normal coagulation pathway,which is a "forced gelation" process mediated by the high concetration/content of QS/TA(differed from the low-content coating in Charpter 2).Further,the femoral-artery-injury experiment of heparinized anticoagulant rats also verified this "forced gelation" procoagulant effect.Finally,ternary composite gels were prepared by mixing different concentrations of QS/TA solution(the fixed ratios of 10:1)and thermosensitive polymer(F127),in order to further verify the procoagulant mechanism of QS/TA complex in the full range from low to high content.In conclusion,the functional complex of quaternized starch and tannic acid has been constructed to explore/optimize the the construction of hemostatic coatings and sponges.The hemostatic performance and procoagulant mechanism of such two hemostatic materials were invstigated in details by in vitro & in vivo experiments.This research work not only develops new hemostatic materials with promisng clinical applications,but also provides new research approaches in the field of hemostatic materials.