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止血材料
MOLECULES · 2022 ·Vol. 27 ·期 8 ·2571 · IF 4.927

Preparation of Chitosan/Clay Composites for Safe and Effective Hemorrhage Control

Zhiyuan Yang,Tong Ye,Fei Ma,Xinhong Zhao,Lei Yang,Guifang Dou,Hui Gan,Zhuona Wu,Xiaoxia Zhu,Ruolan Gu,Zhiyun Meng

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.Keywords:chitosan;kaolin;montmorillonite;hemostatic material;hemorrhage control

CAS / MDL: 9012-76-4
研究领域: 材料科学 · 生物医学工程 · 止血
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Scientific Reports · 2017 ·Vol. 7 ·期 1 ·1-10 · IF 4.259

Minimally Invasive Hemostatic Materials: Tackling a Dilemma of Fluidity and Adhesion by Photopolymerization in situ

Zhang Yun,Song Dandan,Huang Hong,Liang Zhiling,Liu Houhe,Huang Yugang,Zhong Cheng,Ye Guodong

Hemostasis in vivo is a key to success in minimally invasive surgery (MIS). However, solid hemostatic materials cannot pass through the sheath tube of the MIS apparatus, while liquid ones are restricted by their low adhesion, which leads to them peeling off of tissue. To tackle the dilemma of fluidity and adhesion, a formulation containing a multifunctional sucrose allyl ether (SAE) monomer and an alpha-hydroxyketone liquid photoinitiator (HMPP) was applied as a lead hemostatic material for MIS. Real-time infrared results showed that SAE initiated by HMPP can rapidly polymerize into a transparent crosslinking membrane. Quantum chemistry showed that this occurs via a free radical addition reaction mechanism. Thermodynamic properties, such as reaction driving force and enthalpy change, were similar to those for a corresponding small molecular analogue, allyl methyl ether (AME), but the addition rate was lower than that for AME. The CC50 values of SAE and HMPP were also obtained by cell experiments. A hemostasis experiment in vivo was performed by comparing the formulation with chitosan and a traditional Chinese medicine (Yunnan Baiyao powder). The result showed that the formulation had a competitive advantage for use in MIS.

研究领域: 生物医学工程 · 外科手术
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CARBOHYDRATE POLYMERS · 2017 · IF 4.811

Preparation and evaluation of chitosan/alginate porous microspheres/Bletilla striata polysaccharide composite hemostatic sponges

Chao Wang,Wenfeng Luo,Puwang Li,Sidong Li,Ziming Yang,Zhang Hu,Yangyang Liu,Ningjian Ao

We prepared a novel hemostatic material using chitosan (CS), alginate , and Bletilla striata , which showed good biocompatibility and hemostatic properties. Alginate-calcium porous microspheres (Alg) were prepared by emulsification/cross-linking methods, and Bletilla striata polysaccharide (Bsp) was extracted from the tubers by water extraction and alcohol precipitation. To improve the water absorption and accelerate the blood coagulation, Alg and Bsp were mixed with chitosan solution to form CS/Alg and CS/Alg/Bsp composite sponges by lyophilization. Based on SEM images, the microspheres exhibited good spherical shape, possessed many pores on the surface, and were well dispersed in the CS/Alg5 and CS/Alg10 composite sponges. The CS/Alg10 composite sponges showed higher water absorption and porosity. In addition, the cytotoxicity assay and hemostatic property of the CS/Alg and CS/Alg/Bsp composite sponges were tested by CCK-8 assay, in vitro blood clotting, red blood cell (RBC) adhesion, and rabbit ear artery bleeding. These ternary composite sponges could be used as potential novel hemostatic materials in surgical treatment.

CAS / MDL: 9012-76-4
研究领域: 生物材料学 · 医学工程 · 药剂学
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ACS Applied Bio Materials · 2021 · IF 0

Thrombin-Loaded TA-CaCO3 Microspheres as a Budget, Adaptable, and Highly Efficient Hemostatic

Pengzhong Shi,Daozhen Zhou,Yaxin Zhu,Bo Peng,Nannan Shao,Xingjie Zan

Fast hemostasis, biosecurity, and adaptation of different bleeding sites are the major challenges for hemostatic materials. In this work, an easy-to-make, rapid hemostatic, tannic acid doped calcium carbonate microsphere with a low concentration of thrombin (Thr@TA-CaCO3) was developed. In an in vitro blood clotting assay, the hemostatic effect of Thr@TA-CaCO3 varied with the change of thrombin amount. Furthermore, the average hemostatic time can be reduced from 205 to 20 s as the thrombin levels are elevated. When applied in different hemorrhage models, the Thr@TA-CaCO3-treated group had a lower blood loss than the tannic acid modified CaCO3 (TA-CaCO3) groups. Especially in the rabbit artery injury model, the total bleeding amount in the Thr@TA-CaCO3-treated group was only 11.97% of that in the TA-CaCO3 groups, proving that Thr@TA-CaCO3 had an excellent hemostatic effect even in the case of rapidly flowing blood. Based on the above, Thr@TA-CaCO3 is a promising hemostatic agent and can be applied in more extensive clinical applications.

研究领域: 生物医学工程 · 材料科学 · 血液学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Photoresponsive protamine ionic complex towards a smart hemostatic biomaterial

Yun Liu,Guoqiang Zhang,Jia Chen,Ziying Zhang,Quanxin Wu,Lei Zhang,Shanhui Zhu,Qikai Liang,Zhongtao Wu,Xiliang Luo,Zhen Wang,Weishen Zeng

Protamine (PA) is the only licensed antidote for reversing heparin anticoagulation by electrostatically binding with heparin. Efforts have been made on designing various heparin-scavengers, while, it remains a great challenge for gaining the external-stimuli responsive PA-release material. In this study, a generic strategy is developed for fabricating photoresponsive protein materials with the designed azobenzene-containing surfactant. For the first time, based on the isomerization of azobenzene, both cationic and anionic proteins could be phase change biomaterials which are capable of transiting to isotropic state under UV irradiation at room temperature. The formation of isotropic state could set the proteins free from the binding state, activating their intrinsic biological functions. Employing this mechanism, one smart PA material for inhibiting heparin is developed, which could effectively photo-modulate the heparin concentration by turning on-and-off the free state of PA from the binding state. With good biocompatibility, the PA material addresses photoresponsive hemostatic activity in biological studies, confirming its great potential clinical values. This work provides a new designing strategy for gaining photocontrollable hemostasis materials, also opening new opportunities for developing photoresponsive protein drugs and biomedical materials.

研究领域: 生物医学工程 · 材料科学 · 药物开发
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Mechanically enhanced chitosan hydrogels based on micellar cross-linking for wound hemostasis

Yanhao Liu,Shubin Li,Jiang Zhu,Lili Fan,Lu Wang

Excessive blood loss caused by severe trauma is often life-threatening, so a kind of hemostatic material with superior performance is urgently needed to achieve rapid hemostasis of wounds. Here, we prepared CDCS/PF/PVA/Agar hydrogels by blending chitosan modified by catechol groups, PF127-NH 2 micelles, PVA and agarose. The hydrogel showed adjustable swelling and degradation properties. The CDCS/PF/PVA/Agar hydrogel exhibited exceptional mechanical properties with an elastic modulus of 351.4 kPa after four freeze-thaw cycles, surpassing traditional polysaccharide hydrogels by 7–20 fold. Its tissue adhesion strength reached 16.24 kPa in air and 11.23 kPa under wet conditions, enabled by catechol-mediated covalent bonding and amino group interactions. In vivo experiments demonstrated rapid hemostasis within 170 s in mouse liver injury models, reducing blood loss by 75.4 % compared to untreated controls. This study provides a robust strategy for designing polysaccharide hydrogels integrating mechanical resilience, rapid hemostasis, antibacterial activity, and biosafety, offering significant potential for clinical wound management.

研究领域: 生物医学工程 · 材料科学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Epidermal growth factor-incorporated hydrogen bond crosslinked hemostatic microparticles capable of timely response to accidental bleeding for prehospital rescue

Wenguang Dou,Xiaojun Zeng,Chenyang Zhang,Xue Wang,Ye Zhu,Shuzhuang Zhu,Chan Liu,Weijun Ji,Qingmei Fan,Yonglin Gao,Kongyin Zhao,Jin Zhao,Xin Hou,Xubo Yuan,Hongliang Liu,Yansheng Li,Sidi Li

Prehospital rescue of accidental massive bleeding is crucial for saving lives. However, currently available hemostatic materials are still in infancy in treating accidental bleeding due to the challenges in fully satisfying the complex outdoor hemostatic requirements. Herein, we designed an epidermal growth factor (EGF)- incorporated, microparticle-formed, high-strength, dynamic environment-stable hemostatic gel system for prehospital rescue. Carboxyl and dimethylamide were employed as the hydrogen bond (H-bond) groups and were carefully engineered into the microparticles (DHMs). We demonstrated that the unique H-bond crosslinked micronized structure enabled the DHM-based gelling system to adequately meet the outdoor hemostatic requirements. The stable H-bond groups allow the DHMs to be stored at room temperature and be easily carried around. The small sizes (150–250 μm) of the DHMs enabled the filling of irregular defects, and upon encountering water, these DHMs integrated into hydrogels (DHMs-gels) with high mechanical strength (1.61 MPa), strong tissue adhesiveness (66.5 kPa) and stable performance under dynamic environments. In vivo results showed that the EGF-incorporated DHMs-gels (DHMs-EGF gel) achieved a 100 % survival rate in a simulated rescue process and promoted wound healing. Simultaneously possessing multiple prehospital rescue-required properties, the hemostatic DHMs-EGF may become an effective tool for emergency rescue.

CAS / MDL: 79-41-4
研究领域: 生物医学工程 · 创伤急救 · 组织修复
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 36 ·8282-8293 · IF 5.344

A novel injectable starch-based tissue adhesive for hemostasis

Ruihua Cui,Fangping Chen,Yujiao Zhao,Wenjie Huang,Changsheng Liu

Hemorrhage remains one of the direct causes of high mortality. The development of ideal hemostatic materials with sound ability to deal with severe wound is urgent needed. Although starch-based hemostatic powder has been widely used, hydrous physiological environments severely hamper its binding to the target tissue, thereby limiting the effectiveness in hemostasis. Herein, inspired by mussel adhesive protein, a novel injectable tissue-adhesive hydrogel (St-Dopa hydrogel) composed of starch, succinic anhydride and dopamine was developed in situ by enzymatic crosslinking. The results show that St-Dopa hydrogels were intimately integrated with biological tissue and formed robust barriers to reduce blood loss. St-Dopa hydrogels exhibited superior capacity for in vitro and in vivo hemostasis as compared with chitin hydrogels. In addition to the ease of operation, St-Dopa hydrogels exhibited rapid sol–gel transition, porous microscopic morphology, good swelling ratio and biodegradability, tissue-like elastomeric mechanical properties and excellent cyto/hemo-compatibility. These results suggest that this newly developed St-Dopa hydrogel is a promising biological adhesive and hemostatic material.

研究领域: 生物医学工程 · 材料科学 · 创伤修复
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Nature Communications · 2021 ·Vol. 12 ·期 1 ·1-11 · IF 14.919

Robust hemostatic bandages based on nanoclay electrospun membranes

Cui Yan,Huang Zongwang,Lei Li,Li Qinglin,Jiang Jinlong,Zeng Qinghai,Tang Aidong,Yang Huaming,Zhang Yi

Death from acute hemorrhage is a major problem in military conflicts, traffic accidents, and surgical procedures, et al. Achieving rapid effective hemostasis for pre-hospital care is essential to save lives in massive bleeding. An ideal hemostasis material should have those features such as safe, efficient, convenient, economical, which remains challenging and most of them cannot be achieved at the same time. In this work, we report a rapid effective nanoclay-based hemostatic membranes with nanoclay particles incorporate into polyvinylpyrrolidone (PVP) electrospun fibers. The nanoclay electrospun membrane (NEM) with 60 wt% kaolinite (KEM1.5) shows better and faster hemostatic performance in vitro and in vivo with good biocompatibility compared with most other NEMs and clay-based hemostats, benefiting from its enriched hemostatic functional sites, robust fluffy framework, and hydrophilic surface. The robust hemostatic bandages based on nanoclay electrospun membrane is an effective candidate hemostat in practical application.

研究领域: 医学 · 材料科学 · 生物工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Selectively oxidized chitin as a degradable and biocompatible hemostat for uncontrolled bleeding and wound healing

Ruochen Ding,Zhan Shu,Jian Yang,Ren Chen

Chitin (CT), one of the most abundant biopolymers, is insoluble in both dilute aqueous solutions and common organic solvents. In traditional hemostatic applications, chitin must be either converted into acid-soluble chitosan by removing acetyl groups or dissolved in an alkaline aqueous solution at −20 °C. However, acetyl groups are more advantageous than amino groups in promoting hemostasis, biocompatibility, biodegradability, and wound healing. A significant challenge remains in retaining acetyl groups while directly preparing a hemostatic agent from chitin without requiring its dissociation. In this study, we have successfully applied oxidized chitin (OCT) as a hemostatic material, which is directly derived from chitin through a TEMPO-mediated selective oxidation of C6 primary hydroxyl groups to carboxyl groups. Due to its significantly higher hydrophilicity compared to chitin, OCT rapidly forms a gel upon contact with blood, efficiently sealing broken blood vessels and facilitating wound healing. Among OCTs with varying carboxylate contents and the commercial chitosan hemostat Celox™, OCT-24 demonstrated not only the best hemostatic performance in some injury models but also excellent biocompatibility and biodegradability, effectively preventing tissue adhesion and promoting wound healing. The selective oxidation offers a straightforward method for developing a highly effective hemostatic material from chitin to address uncontrolled massive bleeding.

研究领域: 生物医学工程 · 材料科学 · 血液学
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JOURNAL OF POLYMER SCIENCE · 2024 · IF 3.9

Preparation of fluorinated chitosan-based multifunctional materials with rapid hemostasis, anti-infection, and non-adhesive properties for wounds

Yufang Ren,Zeyuan Sun,Yong Huang,Xiaoyan An,Xiaona Bian,Zhenhao Cao,Yifan Liu,Kanwal Javed,Tetiana Derkach,Xue Li

Excessive bleeding can give rise to a range of pathologies, encompassing hypothermia, coagulation disorders, infection, and hemorrhagic shock. Uncontrolled massive blood loss stands as one of the foremost contributors to mortality. Consequently, higher requirements are put forward for the promptness and efficacy of hemostasis. At present, the hemostatic materials available on the market still have the problem that the hemostatic effect is not ideal, the antibacterial effect is poor, which is easy to cause wound infection, and the removal of hemostatic materials will cause secondary bleeding. The present study describes the development of a novel multifunctional hemostatic material based on carboxymethyl chitosan (CMC). First, the fluorinated CMC (CMC-FDA) is successfully synthesized via the Michael addition reaction utilizing 1H, 1H, 2H, 2H -fluorodecyl alcohol (FDA), followed by the preparation of CMC-FDA/PHMB materials through electrostatic interactions with polyhexamethylene biguanide (PHMB). The successful synthesis of CMC-FDA/PHMB was characterized by XPS, FT-IR, NMR, and so forth. The CMC-FDA/PHMB coating exhibits excellent hemostatic properties through in vivo liver hemostasis and in vitro caudation hemostasis experiments. The hemostatic effect of CMC-FDA/PHMB is highly pronounced, as evidenced by the results obtained for hemostasis time and blood loss. The experiment of simulating dynamic blood loss further confirmed that the gauze coated with CMC-FDA/PHMB has excellent hemostatic performance. Moreover, the synthesized CMC-FDA/PHMB coating demonstrates significant anti-adhesion and antibacterial properties of Staphylococcus aureus and Escherichia coli , which could prevent of wound infection. Furthermore, the CMC-FDA/PHMB coating exhibits non-wettability due to its low surface energy of FDA, which can prevent blood wetting and thus play a hemostatic effect, synergistically with CMC. Additionally, the CMC-FDA/PHMB coating demonstrates easy separation from the wound site attributed to it hydrophobic property. The results of the hemolysis and cytotoxicity tests verified the excellent biocompatibility of the CMC-FDA/PHMB coating. This CMC-FDA/PHMB material hold promising potential for rapid hemostasis and prevention of wound infection. Graphical

CAS / MDL: 83512-85-0
研究领域: 生物医学工程 · 材料科学 · 药学
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Bioactive Materials · 2021 · IF 14.593

Improved hemostatic effects by Fe3+ modified biomimetic PLLA cotton-like mat via sodium alginate grafted with dopamine

Caili Lv,Linlong Li,Zixue Jiao,Huanhuan Yan,Zongliang Wang,Zhenxu Wu,Min Guo,Yu Wang,Peibiao Zhang

The development of an excellent, bioabsorbable hemostatic material for deep wound remains a challenge. In this work, a biodegradable cotton-like biomimetic fibrous mat of poly ( l -lactic acid) (PLLA) was made by melt spinning. Subsequently, SD composite was prepared by cross-linking sodium alginate (SA) with dopamine (DA). It was immobilized on the fibre surface, which inspired by mussel byssus. Finally, Fe 3+ was loaded onto the 0.5SD/PLLA composite by chelation with the carboxyl of alginate and phenolic hydroxy of dopamine. The haemostasis experiment found that the hemostatic time 47 s in vitro. However, the bleeding volume was 0.097 g and hemostatic time was 23 s when 20Fe 3+ -0.5SD/PLLA was applied in the haemostasis of the rat liver. As a result of its robust hydrophilicity and bouffant cotton-like structure, it could absorb a large water from blood, which could concentrate the component of blood and reduce the clotting time. Furthermore, the addition of Fe 3+ in the 0.5SD/PLLA had a significant effect on improve hemostatic property. It also displayed excellent antibacterial property for Escherichia coli and Staphylococcus aureus . Notably, it possesses superior hemocompatibility, cytocompatibility and histocompatibility. Hence, 20Fe 3+ -0.5SD/PLLA has high potential application in haemostasis for clinical settings due to its outstanding properties.

研究领域: 生物医学工程 · 材料科学 · 血液学
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