Contents lists available at ScienceDirectMaterials Science & Engineering Cjournal homepage: www.elsevier.com/locate/msecHemostatic porous sponges of cross-linked hyaluronic acid/cationizeddextran by one self-foaming processJia-Ying Liu a,b,1 , Yang Li a,1 , Yang Hu a,? , Gang Cheng c , Enyi Ye d , Chuanan Shen b,? , Fu-Jian Xu a,?aState Key Laboratory of Chemical Resource Engineering, Key Laboratory of Carbon Fiber and Functional Polymers (Ministry of Education), Beijing Laboratory ofBiomedical Materials, Beijing University of Chemical Technology, Beijing 100029, ChinabDepartment of Burn& Plastic Surgery, The First Af f i liated Hospital of General Hospital of PLA, Beijing 100048, ChinacDepartment of Chemical Engineering, University of Illinois at Chicago, Chicago, IL 60607, United StatesdInstitute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Innovis, #08-03, Singapore 138634,SingaporeA R T I C L E I N F OKeywords:HemostaticSpongeSelf-foamingPolysaccharideCationicA B S T R A C TEf f ective hemostatic materials are very important for treating trauma cases. Natural polysaccharides have beenparticularly appealing in the development of new hemostatic materials due to their unique functions in humanbodies. In this work, dif f erent polysaccharide-based hemostatic porous sponges (SHDP or SHDQ) of cross-linkedhyaluronic acid (HA)/cationized dextran were readily prepared by the self-foaming process of HA and poly((2-dimethyl amino)-ethyl methacrylate)-grafted dextran (Dex-PDM) or partially-quaternized Dex-PDM in the pre-sence of sodium trimetaphosphate crosslinkers. SHDP and SHDQ sponges were investigated in terms of liquid-absorption ability, hemolysis, whole-blood clotting and hemostatic activity in hemorrhaging-liver models.Compared with HA/Dex-PDM sponges (HDP) without chemical cross-linking, SHDP and SHDQ sponges dis-played higher porosity (> 70.0% vs. 48.9%) and swelling ratios (> 1000% vs. 520%). Meanwhile, hemolysisassay revealed the good blood compatibility of SHDP and SHDQ with low hemolysis ratio (below 0.5%).Furthermore, in vitro and in vivo hemostatic assay showed that SHDQ possessed better hemostatic properties thanSHDP, owing to the higher cationic charges of partially-quaternized Dex-QPDM than Dex-PDM. The presentstudy demonstrated that the self-foaming process of HA/Dex-PDM under a ‘green’ condition is an ef f ective meansto produce new hemostatic materials.1. IntroductionBleeding stop is a crucial step of the emergency treatment, espe-cially in cases of uncontrolled trauma in major traf f i c accidents, naturaldisasters and battle f i elds [1–3]. Hemorrhage (massive blood loss)normally cannot be controlled by the human body's natural hemostaticmechanism [4]. As a major supplement to traditional surgical techni-ques, a series of hemostatic materials have been explored for thetreatment of hemorrhage in preclinical research and clinical trials[5–7]. In comparison with synthetic polymers and inorganic materialssuch as cyanoacrylates and zeolite, natural materials including f i bringlue, gelatin, and chitosan have been particularly appealing in the de-velopment of hemostatic materials due to their bioactive and uniquebiochemical functions in animal and human bodies [8–11].Among natural materials, cationic chitosan has been recognized asthe optimal one to construct hemostatic materials [11–14]. Aminogroups of chitosan have the ability to interact with the negativelycharged membranes of blood cells and thereby induce platelet ag-gregation, thus endowing chitosan with excellent hemostatic property[13]. However, the application of chitosan is limited by its poor water-solubility in physiological condition. Acetic acid is usually used as theprocessing solvent of chitosan, but it leads to a trace acidulous odor inthe f i nal hemostatic product [14]. Recently, cationic molecules andpolycations had been introduced onto nonionic polysaccharides toconstruct cationized polysaccharides [15–18]. They could realize theinteraction with negatively charged nucleic acids/cell membranes.Moreover, water-solubility of cationized polysaccharides is better thanchitosan in physiological condition. Hence, it is very useful to explorethe feasibility of cationized polysaccharides for ef f ective hemostaticmaterials.Hydrogels and sponges are the common product forms of hemo-static materials [12,19–21] Hydrogels are recognized as ideal injectablehttp://dx.doi.org/10.1016/j.msec.2017.10.007Received 3 October 2017; Accepted 25 October 2017? Correspondence authors.1 Both authors contributed equally to this work.E-mail addresses: huyang@mail.buct.edu.cn (Y. Hu), shenchuanan@126.com (C. Shen), xufj@mail.buct.edu.cn (F.-J. Xu).Materials Science & Engineering C xxx (xxxx) xxx–xxx0928-4931/ © 2017 Elsevier B.V. All rights reserved.Please cite this article as: Liu, J.-Y., Materials Science & Engineering C (2017), http://dx.doi.org/10.1016/j.msec.2017.10.007
