{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T20:43:43Z","timestamp":1785357823639,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Natural and Science","award":["No. 7202148"],"award-info":[{"award-number":["No. 7202148"]}]},{"name":"Beijing Science and Technology","award":["No. 1916315ZD00900101"],"award-info":[{"award-number":["No. 1916315ZD00900101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Uncontrolled hemorrhage from trauma or surgery can lead to death. In this study, chitosan\/kaolin (CSK) and chitosan\/montmorillonite (CSMMT) composites were prepared from chitosan (CS), kaolin (K), and montmorillonite (MMT) as raw materials to control bleeding. The physiochemical properties and surface morphology of CSK and CSMMT composites were analyzed by Fourier transform infrared spectrometry (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), zeta potentials, and X-ray fluorescence (XRF). The hemostatic mechanism was measured in vitro by activated partial thromboplastin time (APTT), prothrombin time (PT), in vitro clotting time, erythrocyte aggregation, and thromboelastogram (TEG). The hemostasis ability was further verified by using tail amputation and arteriovenous injury models in rats. The biocompatibility of CSK and CSMMT was evaluated by in vitro hemolysis, cytotoxicity assays, as well as acute toxicity test and skin irritation tests. The results show that CSK and CSMMT are promising composite materials with excellent biocompatibility and hemostatic properties that can effectively control bleeding.<\/jats:p>","DOI":"10.3390\/molecules27082571","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T01:03:01Z","timestamp":1650330181000},"page":"2571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Preparation of Chitosan\/Clay Composites for Safe and Effective Hemorrhage Control"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhiyuan","family":"Yang","sequence":"first","affiliation":[{"name":"College of pharmacy, Henan University, Kaifeng 475000, China"},{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Ye","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Ma","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifang","family":"Dou","sequence":"additional","affiliation":[{"name":"College of pharmacy, Henan University, Kaifeng 475000, China"},{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gan","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuona","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolan","family":"Gu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyun","family":"Meng","sequence":"additional","affiliation":[{"name":"College of pharmacy, Henan University, Kaifeng 475000, China"},{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/j.1553-2712.2011.01036.x","article-title":"Comparison of Celox-A, ChitoFlex, WoundStat, and combat gauze hemostatic agents versus standard gauze dressing in control of hemorrhage in a swine model of penetrating trauma","volume":"18","author":"Littlejohn","year":"2011","journal-title":"Acad. Emerg. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1016\/j.biomaterials.2009.10.023","article-title":"The performance of a fly-larva shell-derived chitosan sponge as an absorbable surgical hemostatic agent","volume":"31","author":"Gu","year":"2010","journal-title":"Biomaterials"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1046\/j.1538-7836.2003.00062.x","article-title":"Hemostasis and irreducible complexity","volume":"1","author":"Aird","year":"2003","journal-title":"J. Thromb. Haemost."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.ejvs.2006.10.011","article-title":"Various local hemostatic agents with different modes of action; an in vivo comparative randomized vascular surgical experimental study","volume":"33","author":"Holst","year":"2007","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.1007\/s00586-004-0727-z","article-title":"The use of local agents: Bone wax, gelatin, collagen, oxidized cellulose","volume":"13","author":"Schonauer","year":"2004","journal-title":"Eur. Spine. J."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pomini, K.T., Buchaim, D.V., Andreo, J.C., Rosso, M.P.O., Della Coletta, B.B., German, \u00cd.J.S., Biguetti, A.C.C., Shinohara, A.L., Rosa J\u00fanior, G.M., and Cosin Shindo, J.V.T. (2019). Fibrin Sealant Derived from Human Plasma as a Scaffold for Bone Grafts Associated with Photobiomodulation Therapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071761"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1160\/TH03-08-0526","article-title":"Fibrin glue for wound repair: Facts and fancy","volume":"90","author":"Clark","year":"2003","journal-title":"Thromb. Haemost."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.bcmd.2005.12.016","article-title":"Collagen-induced platelet activation","volume":"36","author":"Farndale","year":"2006","journal-title":"Blood. Cells Mol. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/j.1538-7836.2004.00665.x","article-title":"The role of collagen in thrombosis and hemostasis","volume":"2","author":"Farndale","year":"2004","journal-title":"J. Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.carbpol.2017.06.112","article-title":"Preparation and evaluation of chitosan\/alginate porous microspheres\/Bletilla striata polysaccharide composite hemostatic sponges","volume":"174","author":"Wang","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1097\/01.TA.0000105916.30158.06","article-title":"Thermal injury resulting from application of a granular mineral hemostatic agent","volume":"57","author":"Wright","year":"2004","journal-title":"J. Trauma"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.amsu.2014.03.001","article-title":"The effects of QuikClot Combat Gauze on hemorrhage control in the presence of hemodilution and hypothermia","volume":"3","author":"Johnson","year":"2014","journal-title":"Ann. Med. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1166\/jnn.2016.10923","article-title":"Glutaraldehyde Cross-Linked Chitosan Nanofibers: Preparation, Characterization and Application in Adsorption of Cu (II)","volume":"16","author":"Cao","year":"2016","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Matica, M.A., Aachmann, F.L., T\u00f8ndervik, A., Sletta, H., and Ostafe, V. (2019). Chitosan as a Wound Dressing Starting Material: Antimicrobial Properties and Mode of Action. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235889"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jss.2014.06.019","article-title":"Hydrophobically-modified chitosan foam: Description and hemostatic efficacy","volume":"193","author":"Dowling","year":"2015","journal-title":"J. Surg. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1016\/j.biomaterials.2008.07.034","article-title":"Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties","volume":"29","author":"Ong","year":"2008","journal-title":"Biomaterials"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"497","DOI":"10.7205\/MILMED-D-13-00199","article-title":"Review of new topical hemostatic dressings for combat casualty care","volume":"179","author":"Bennett","year":"2014","journal-title":"Mil Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ijbiomac.2009.03.010","article-title":"Chitosan topical gel formulation in the management of burn wounds","volume":"45","author":"Alsarra","year":"2009","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hu, Z., Lu, S., Cheng, Y., Kong, S., Li, S., Li, C., and Yang, L. (2018). Investigation of the Effects of Molecular Parameters on the Hemostatic Properties of Chitosan. Molecules, 23.","DOI":"10.3390\/molecules23123147"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.biotechadv.2011.01.005","article-title":"Biomaterials based on chitin and chitosan in wound dressing applications","volume":"29","author":"Jayakumar","year":"2011","journal-title":"Biotechnol. Adv."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Aguilar, A., Zein, N., Harmouch, E., Hafdi, B., Bornert, F., Offner, D., Clauss, F., Fioretti, F., Huck, O., and Benkirane-Jessel, N. (2019). Application of Chitosan in Bone and Dental Engineering. Molecules, 24.","DOI":"10.3390\/molecules24163009"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1002\/tcr.201700072","article-title":"Functional Kaolinite","volume":"18","author":"Detellier","year":"2018","journal-title":"Chem. Rec."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.ijbiomac.2020.05.140","article-title":"Efficient antibacterial dextran-montmorillonite composite sponge for rapid hemostasis with wound healing","volume":"160","author":"Liu","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"110649","DOI":"10.1016\/j.msec.2020.110649","article-title":"Tough polyacrylamide-tannic acid-kaolin adhesive hydrogels for quick hemostatic application","volume":"109","author":"Fan","year":"2020","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gan, C., Hu, H., Meng, Z., Zhu, X., Gu, R., Wu, Z., Wang, H., Wang, D., Gan, H., and Wang, J. (2019). Characterization and Hemostatic Potential of Two Kaolins from Southern China. Molecules, 24.","DOI":"10.3390\/molecules24173160"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.thorsurg.2011.08.002","article-title":"Advances in the management of esophageal perforation","volume":"21","author":"Carrott","year":"2011","journal-title":"Thorac. Surg. Clin."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1346\/CCMN.1986.0340109","article-title":"Lysis of Erythrocytes by Silicate Minerals","volume":"34","author":"Oscarson","year":"1986","journal-title":"Clays. Clay. Miner."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ijbiomac.2018.11.045","article-title":"A review on recent advances in chitosan based composite for hemostatic dressings","volume":"124","author":"Khan","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hu, Z., Zhang, D.Y., Lu, S.T., Li, P.W., and Li, S.D. (2018). Chitosan-Based Composite Materials for Prospective Hemostatic Applications. Mar. Drugs, 16.","DOI":"10.3390\/md16080273"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Elsabahy, M., and Hamad, M.A. (2021). Design and Preclinical Evaluation of Chitosan\/Kaolin Nanocomposites with Enhanced Hemostatic Efficiency. Mar. Drugs, 19.","DOI":"10.3390\/md19020050"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.carbpol.2017.08.131","article-title":"Chitosan\/kaolin composite porous microspheres with high hemostatic efficacy","volume":"177","author":"Sun","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24908","DOI":"10.1039\/C5CP04395F","article-title":"New organophilic kaolin clays based on single-point grafted 3-aminopropyl dimethylethoxysilane","volume":"17","author":"Zaharia","year":"2015","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jcis.2018.02.004","article-title":"Effect of intercalated chitosan\/clay nanostructures on concentrated pluronic F127 solution: A FTIR-ATR, DSC and rheological study","volume":"517","author":"Branca","year":"2018","journal-title":"J. Colloid Interface Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.ijbiomac.2019.02.078","article-title":"Chitosan intercalated bentonite as natural adsorbent matrix for water-soluble sappanwood dye","volume":"129","author":"Jimtaisong","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jcis.2004.08.019","article-title":"Competitive sorption of protons and metal cations onto kaolinite: Experiments and modeling","volume":"282","author":"Heidmann","year":"2005","journal-title":"J. Colloid Interface Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.jcis.2017.06.071","article-title":"Spectral induced polarization of Na-montmorillonite dispersions","volume":"505","author":"Leroy","year":"2017","journal-title":"J. Colloid Interface Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.jcis.2018.08.100","article-title":"Enhanced selectivity and performance of heterogeneous cation exchange membranes through addition of sulfonated and protonated Montmorillonite","volume":"533","author":"Radmanesh","year":"2019","journal-title":"J. Colloid Interface Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1213\/ANE.0000000000003457","article-title":"Mixing Studies in Patients with Prolonged Activated Partial Thromboplastin Time or Prothrombin Time","volume":"128","author":"Benzon","year":"2019","journal-title":"Anesth. Analg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1365-2257.2005.00681.x","article-title":"Thrombelastography\/thromboelastometry","volume":"27","author":"Luddington","year":"2005","journal-title":"Clin. Lab. Haematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1704452","DOI":"10.1002\/adfm.201704452","article-title":"Emerging Nanoclay Composite for Effective Hemostasis","volume":"28","author":"Long","year":"2017","journal-title":"Adv. Funct. Mater."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.colsurfb.2015.10.039","article-title":"Chitosan\/gelatin composite sponge is an absorbable surgical hemostatic agent","volume":"136","author":"Lan","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1021\/acs.biomac.7b01492","article-title":"Exploration of Blood Coagulation of N-Alkyl Chitosan Nanofiber Membrane in Vitro","volume":"19","author":"Wang","year":"2018","journal-title":"Biomacromolecules"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4952","DOI":"10.1039\/D0BM02116D","article-title":"Thrombin immobilized polydopamine-diatom biosilica for effective hemorrhage control","volume":"9","author":"Mu","year":"2021","journal-title":"Biomater. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"116051","DOI":"10.1016\/j.carbpol.2020.116051","article-title":"Hydroxybutyl chitosan\/diatom-biosilica composite sponge for hemorrhage control","volume":"236","author":"Zhang","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1089\/ten.tea.2020.0174","article-title":"Fabrication of Hydroxypropyl Chitosan\/Soy Protein Isolate Hydrogel for Effective Hemorrhage Control","volume":"27","author":"Zhao","year":"2021","journal-title":"Tissue Eng. Part A"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"117634","DOI":"10.1016\/j.carbpol.2021.117634","article-title":"Vasoconstrictor and coagulation activator entrapped chitosan based composite hydrogel for rapid bleeding control","volume":"258","author":"Sundaram","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5096","DOI":"10.1039\/C9TB01019J","article-title":"Emerging chitin nanogels\/rectorite nanocomposites for safe and effective hemorrhage control","volume":"7","author":"Zhang","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0300-9572(95)00829-I","article-title":"Uncontrolled hemorrhagic shock outcome model in rats","volume":"29","author":"Capone","year":"1995","journal-title":"Resuscitation"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.biomaterials.2019.03.016","article-title":"A highly efficient, in situ wet-adhesive dextran derivative sponge for rapid hemostasis","volume":"205","author":"Liu","year":"2019","journal-title":"Biomaterials"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1177\/0885328219888626","article-title":"Safety evaluation of a low-heat producing zeolite granular hemostatic dressing in a rabbit femoral artery hemorrhage model","volume":"34","author":"Chen","year":"2020","journal-title":"J. Biomater. Appl."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"118307","DOI":"10.1016\/j.carbpol.2021.118307","article-title":"Hemocompatibility, biodegradability and acute toxicity of acetylated cellulose nanocrystals of different types in comparison","volume":"269","author":"Torlopov","year":"2021","journal-title":"Carbohydr. 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