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CARBOHYDRATE POLYMERS · 2021 · IF 9.381

Polysaccharides-modified chitosan as improved and rapid hemostasis foam sponges

Xiaohui Wei,Sheng Ding,Shisheng Liu,Kun Yang,Junjie Cai,Fan Li,Chunlai Wang,Song Lin,Feng Tian

Serial hemostatic sponges consisting of polysaccharides-modified chitosan foam sponges were prepared by Schiff base crosslinking reaction between the deacetylated chitosan and oxidized dialdehyde cellulose. Such composite foam sponges were characterized by scanning electron microscopy and Fourier-transform infrared spectroscopy to confirm their morphology and compositions. Then the coagulation process was evaluated in vitro by thrombus elasticity meters. Furthermore, the hemostasis experiments on mouse tail vein and rabbit femoral artery were also performed in vivo . The results strongly indicated that such synergistic cellulose-modified chitosan foam sponges showed comprehensively excellent water-absorbing quality, improved mechanical performance, low hemolysis rates, benign cytotoxicity, good resilience ability after repeated compression, and superior hemostasis capability both in vitro and in vivo . Furthermore, the hemostatic mechanism is via adhering/activating the red blood cell/platelet to form robust blood clots through the endogenous coagulation pathway, which serves as a good candidate for emergency trauma treatment in daily civilian and military hemostasis.

研究领域: 生物材料学 · 医学工程 · 血液学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Marine Drugs · 2025 ·Vol. 23 ·期 2 ·64 · IF 5.4

Structural Characterization and Anticoagulant Potential of Colochirus quadrangularis Fucosylated Glycosaminoglycan 5−12 Oligomers with Unusual Branches

Xuedong Zhang,Guangwei Yan,Xinming Liu,Jiewen Fu,Xiang Shi,Pei Cao,Yuqian Sun,Shengping Zhong,Jiale Nong,Peiqi Jiang,Yonghong Liu,Baoshun Zhang,Qingxia Yuan,Longyan Zhao

The depolymerized products and oligosaccharide fractions from sea cucumber fucosylated glycosaminoglycans (FGs) are promising anticoagulant candidates, and more novel FG-derived oligosaccharides from low-priced sea cucumbers are expected to be obtained. This study isolated 5−12 oligomers (OF1−OF3) with unusual branches from β-eliminative depolymerized products ofColochirus quadrangularisFG (CqFG). Detailed NMR analyses showed that OF1−OF3 consisted of a chondroitin 4,6-sulfates backbone and some sulfated fucosyl branches (FucS), including monosaccharides (α-l-Fuc2S4S, α-l-Fuc3S, α-l-Fuc4S, α-l-Fuc2S3S4S, and α-l-Fuc2S) and a disaccharide D-Gal3S4S-α1,3-l-Fuc2S4Swith the ratio of ~36:35:10:7:3:9, attached to the C-3 position of β-d-GlcA or its derivatives, such as α-l-Δ4,5GlcA and β-d-GlcA-ol. Unusually, α-l-Fuc3Swas the main FucS branch; no α-l-Fuc3S4Sbranch was found, and α-l-Fuc2S3S4Sand α-l-Fuc2Sbranches were also found in OF1–OF3. The OF2 and OF3 could strongly inhibit the intrinsic and common coagulation pathways. Intrinsic FXase is a target of OF2 and OF3 inhibiting the intrinsic coagulation pathways, and the unusual side chains may increase the intrinsic FXase inhibitory activity. OF2 and OF3 showed negligible bleeding risk, and less bleeding than heparin (HP), low-molecular-weight heparins (LMWHs), and CqFG. These findings support novel FG oligosaccharides with some unusual branches from low-priced sea cucumbers to be prepared as safer anticoagulants.

CAS / MDL: 2438-80-4 1772-03-8
研究领域: 海洋生物化学 · 药理学 · 分子生物学
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JOURNAL OF PROTEOME RESEARCH · 2024 · IF 3.8

Proteome and Metabolome Profiling of Anticoagulant Disorders Induced by Familial Protein S Deficiency

Caiping Zhang,Yimin Zhang,Binjie Liu,Yongxv Chen,Yue Xie,Huiting Huang,Zhongqiu Liu,Zhuoru He

Protein S deficiency (PSD) is an autosomal dominant disorder characterized by congenital thrombophilia. Studies on PSD are limited yet, resulting in a lack of clarity about molecular changes during abnormal coagulation. Proteomics and metabolomics analyses were conducted on the plasma of PSD patients based on liquid and gas chromatography–mass spectrometry (LC- and GC–MS). Differential proteins and metabolites of PSD were then filtered by univariate statistical analysis and subjected to network analysis using the ingenuity pathway analysis (IPA) platform. The proteome and metabolome of PSD were obviously disturbed, and the biological pathway of coagulation and complement cascades was the most affected. During PSD, overall levels of anticoagulant protein decreased and negative regulation of thrombin production was reduced, causing the formation of fibrin clots and platelet aggregation. Furthermore, 9 differential proteins correlated significantly with protein S, comprising A2M, AGT, APOE, FGG, GPLD1, IGHV1–69, CFHR5, CPN2, and CA1. The biological networks suggested that the pathways of acute phase response, FXR/RXR activation, serotonin receptor signaling, and p70S6K signaling were associated with PSD, indicating an interaction disorder of inflammatory immune and lipid metabolism. The findings may contribute to knowledge of available functional molecules and biological pathways of familial PSD and help with treatment improvement. Data are available via ProteomeXchange with identifier PXD055111 and MetaboLights with reference number MTBLS2653.

研究领域: 医学 · 生物信息学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF THROMBOSIS AND HAEMOSTASIS · 2022 · IF 16.036

Glycated albumin modulates the contact system with implications for the kallikrein-kinin and intrinsic coagulation systems

Lewis J. Hardy,Dillon Bohinc,Kara L. Bane,Samantha L. Heal,Emma Hethershaw,Majid Ali,Thomas Palmer-Dench,Richard Foster,Colin Longstaff,Thomas Renné,Evi X. Stavrou,Helen Philippou

Background Human serum albumin (HSA) is the most abundant plasma protein and is sensitive to glycation in vivo . The chronic hyperglycemic conditions in patients with diabetes mellitus (DM) induce a nonenzymatic Maillard reaction that denatures plasma proteins and forms advanced glycation end products (AGEs). HSA-AGE is a prevalent misfolded protein in patients with DM and is associated with factor XII activation and downstream proinflammatory kallikrein-kinin system activity without any associated procoagulant activity of the intrinsic pathway. Objectives This study aimed to determine the relevance of HSA-AGE toward diabetic pathophysiology. Methods The plasma obtained from patients with DM and euglycemic volunteers was probed for activation of FXII, prekallikrein (PK), and cleaved high-molecular-weight kininogen by immunoblotting. Constitutive plasma kallikrein activity was determined via chromogenic assay. Activation and kinetic modulation of FXII, PK, FXI, FIX, and FX via in vitro –generated HSA-AGE were explored using chromogenic assays, plasma-clotting assays, and an in vitro flow model using whole blood. Results Plasma obtained from patients with DM contained increased plasma AGEs, activated FXIIa, and resultant cleaved cleaved high-molecular-weight kininogen. Elevated constitutive plasma kallikrein enzymatic activity was identified, which positively correlated with glycated hemoglobin levels, representing the first evidence of this phenomenon. HSA-AGE, generated in vitro , triggered FXIIa-dependent PK activation but limited the intrinsic coagulation pathway activation by inhibiting FXIa and FIXa-dependent FX activation in plasma. Conclusion These data indicate a proinflammatory role of HSA-AGEs in the pathophysiology of DM via FXII and kallikrein-kinin system activation. A procoagulant effect of FXII activation was lost through the inhibition of FXIa and FIXa-dependent FX activation by HSA-AGEs.

研究领域: 医学 · 生物化学
✓ 已验证 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2024 · IF 5.4

Sodium alginate/carboxycellulose/polydopamine composite microspheres for rapid hemostasis of deep irregular wounds

Junjie Hu,Yinchun Hu,Min Kang,Xuanyu Liu,Baogang Wu,Lining Wang,Yan Wei,Di Huang

Hemostasis of deep irregular wounds is a severe problem in clinical practice. The development of rapid-acting hemostatic agents for deep and irregular wound is urgently needed. Here, sodium alginate/carboxycellulose/polydopamine (SA/CNF/PDA) microspheres was prepared by reverse emulsification and crosslinking with Ca 2+ , and SA/CNF/PDA composite hemostatic microspheres with porous structure were obtained by freeze-drying. SA/CNF/PDA composite hemostatic microspheres exhibited excellent porosity and water absorption which could rapidly absorb blood on the wound surface. Moreover, SA/CNF/PDA composite microspheres demonstrated remarkable hemostatic capabilities both in vitro and in vivo. It exhibited strong hemostatic performance in models of mouse tail-break and liver damage. Especially in liver injury model, it was completely hemostatic in 95 s, and blood loss (19.3 mg). The hemostatic efficacy of the SA/CNF/PDA composite microspheres was amplified through the stimulation of both exogenous and endogenous coagulation pathways. Therefore, SA/CNF/PDA composite hemostatic microspheres are suitable for rapid hemostasis of deep irregular wounds which are potential rapid hemostatic material for surgical application.

CAS / MDL: 62-31-7 1338-43-8
研究领域: 生物材料学 · 医学工程 · 创伤修复
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RSC Advances · 2016 ·Vol. 6 ·期 98 ·95358-95368 · IF 3.289

Preparation and characterization of a chitin/platelet-poor plasma composite as a hemostatic material

Lingmei Lv,Fengling Tang,Guangqian Lan

The development of life-saving hemostatic materials for emergencies can reduce death caused by uncontrolled hemorrhaging. In this study, we developed a composite hemostatic material based on interactions between chitin and platelet-poor plasma (PPP) that promote in situ thrombin attachment to the chitin surface. Optimal conditions for preparing the chitin/PPP composite hemostatic material (CP), including reaction time, temperature, inducing ion, and thrombin concentration, were determined; thrombin activity and PPP clotting time were then measured under these conditions. We found that chitin and 2-fold-diluted PPP induced with 0.2 mol L−1 CaCl2 and reacted in a 35 °C water bath for 1 h yielded the fastest clotting time in vitro (75.0 ± 3.0 s). Furthermore, CP showed a more potent hemostatic effect than chitin in a rabbit model of arterial and hepatic bleeding, which was attributable to the strong adsorption of thrombin. The activated partial thromboplastin time revealed that CP promoted blood coagulation via activation of the endogenous coagulation pathway. CP caused no obvious cytotoxicity in L929 cells, and histopathological examination indicated that CP had no immunogenicity, and accelerated wound healing. These results highlight the potential for using CP as a hemostatic agent in clinical settings.

研究领域: 生物材料 · 止血 · 生物医学工程 · 临床医学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Development of bovine serum albumin-modified Fe3O4 embedded in porous α-ketoglutaric acid/chitosan (BSA/Fe3O4@KA/CS): A magnetically targeted hemostatic dressing for deep and irregular wounds

Jinnan Guo,Yuanyuan Zhao,Guanqun Peng,Tong Ye,Xiaohui Zhu,Runtian Li,Jintao Shen,Lina Du,Shanshan Wang,Zhiyun Meng,Hui Gan,Ruolan Gu,Wenzhong Sun,Guifang Dou,Shuchen Liu,Yunbo Sun

Severe bleeding from deep and irregular wounds poses a significant challenge in prehospital and surgical settings. To address this issue, we developed a novel chitosan-based hemostatic dressing with a magnetic targeting mechanism using Fe 3 O 4 , termed bovine serum albumin-modified Fe 3 O 4 embedded in porous α-ketoglutaric acid/chitosan (BSA/Fe 3 O 4 @KA/CS). This dressing enhances hemostasis by magnetically guiding the agent to the wound site. In vitro, the hemostatic efficacy of BSA/Fe 3 O 4 @KA/CS is comparable to that of commercial chitosan (Celox™) and is not diminished by the modification. In vivo, BSA/Fe 3 O 4 @KA/CS demonstrated superior hemostatic performance and reduced blood loss compared to Celox™. The hemostatic mechanism of BSA/Fe 3 O 4 @KA/CS includes the concentration of solid blood components through water absorption, adherence to blood cells, and activation of the endogenous coagulation pathway. Magnetic field targeting is crucial in directing the dressing to deep hemorrhagic sites. Additionally, safety assessments have confirmed the biocompatibility and biodegradability of BSA/Fe 3 O 4 @KA/CS. In conclusion, we introduce a novel approach to modify chitosan using magnetic guidance for effective hemostasis, positioning BSA/Fe 3 O 4 @KA/CS as a promising candidate for managing various wounds.

研究领域: 生物材料 · 止血 · 伤口愈合 · 纳米技术 · 生物医学工程
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Food Science and Human Wellness · 2022 · IF 8.022

Structural characteristics, anticoagulant and antithrombotic mechanism of a novel polysaccharide from Rosa Chinensis Flos

Xiaofeng Zhang,Zhenhua Liang,Geoffrey Ivan Neil Waterhouse,Shengjun Jiang,Dongxiao Sun-Waterhouse,Jinmei Wang,Changyang Ma,Wenyi Kang

This is the first report on a polysaccharide (RCJ2-Ib) isolated from Rosa Chinensis Flos. RCJ2-Ib was obtained through the extraction with water, precipitation with ethanol, separation with DEAE-52 column and purification with DEAE-Sepharose Fast Flow column and Sephadex G100 column. GC, FT-IR and NMR analyses revealed that RCJ2-Ib (3.3 kDa) was a 1,4-linked polymannuronic acid containing substantial β - D -anomers units. The anticoagulant effect of RCJ2-Ib evaluated by using rabbit ear venous blood and an acute blood stasis rat model showed that RCJ2-Ib had obvious anticoagulant activity in regulating endogenous and exogenous coagulation pathways and reducing serum thromboxane B2 and endothelin-1. In addition, RCJ2-Ib could also increase the number of Lactobacillus and Escherichia coli . As a result, RCJ2-Ib has the potential to inhibit thrombosis and maintain the intestinal environment.

CAS / MDL: 76-05-1
研究领域: 药理学 · 生物化学 · 医学
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SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS · 2023 · IF 5.5

Mesoporous bioactive glass nanoparticles with biomineralization activity for surgical hemorrhage control

Shengyu Li,Xijin Wu,Jianglin Chen,Jinwei Wang,Lihong Gong,Jianyu Ni,Saifei Xi,Hong Zhang,Huiying Fu,Qiyang Shou

Bioactive glass nanoparticles (BGNs) are good bioactive materials for clinical treatment because of their unique composition and silica-oxygen network structure. Herein, we designed and reported a monodisperse mesoporous bioactive glass nanoparticle with biomineralization activity for surgical hemorrhage control. The results indicated that the BGNs have excellent biomineralization ability. In vivo and in vitro hemostasis studies suggested that BGNs have superior hemostatic properties to GZ (gauze) and GS (commercial gelatin sponge) and validated in vitro thrombosis, platelet adhesion, cytocompatibility and blood compatibility. The particles activated both endogenous and exogenous physiological coagulation pathways and could activate platelets and release Ca2+ to participate in the clotting pathway. Besides, the BGNs have good biocompatibility in vivo. These findings demonstrated that the potential of small diameter mesoporous bioactive glass nanoparticles is likely useful for bleeding control as potential hemostatic agents.

研究领域: 生物材料 · 纳米技术 · 止血剂 · 生物医学工程
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Advanced Healthcare Materials · 2023 ·Vol. 12 ·期 21 ·2300075 · IF 10

High-Efficiency Antibacterial Hemostatic AgNP@Zeolite/Chitin/Bamboo Composite Sponge for Wound Healing without Heat Injury

Lu Zheng,Xiaoyun Li,Changliang Xu,Yidi Xu,Yukai Zeng,Manseng Tam,Huan-Tian Zhang,Xiaoying Wang

Chitin is a popular hemostatic material, but there are still many deficiencies in its ability to effectively stop bleeding, prevent infection, and fit wounds. Herein, AgNP@zeolite/chitin/bamboo (AgZ-CB) composite sponges with shape recovery are prepared to minimize blood loss, kill bacteria, and promote wound healing. Notably, the bamboo powder is used for the first time to remarkably enhance the softness of the composite sponge (volumetric expansion ratio >5). The fabricated AgZ-CB sponge exhibits an excellent killing effect (≈100% bactericidal rate) against both Escherichia coli and Staphylococcus aureus and activates internal and external coagulation pathways to accelerate hemostasis without causing thermal damage (≈5 °C temperature difference). Moreover, the AgZ-CB sponge shows less blood loss (26 mg) and a shorter time to hemostasis (42 s) than the commercial polyvinyl formal sponge (84 mg and 76 s) in the full-thickness liver injury model. The in vivo wound healing and biodegradation experiment indicate that AgZ-CB with excellent biocompatibility can close wounds efficiently. Overall, the AgZ-CB sponge has great potential in combating a series of obstacles in wound healing.

CAS / MDL: 106-89-8 7761-88-8
研究领域: 材料科学 · 生物医学工程 · 伤口护理
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CHEMICAL ENGINEERING JOURNAL · 2022 · IF 16.744

Injectable and ultra-compressible shape-memory mushroom: Highly aligned microtubules for ultra-fast blood absorption and hemostasis

Shuai Fan,Xiaozhuo Wu,Zilong Fang,Ganghua Yang,Jianqiu Yang,Wen Zhong,Jun Luo,Malcolm Xing,Wenbing Wan

Noncompressible bleeding is associated with a significant source of traumatic fatality. Due to its inaccessibility to the pressure dressing, patients admitted with internal bleeding mainly rely on blood transfusion, coming with a high cost and immunological side effects. Injectable materials have emerged as a strategy; however, they have limitations on either large mechanical compressibilty or blood clotting speed and blood absorbing capacity. Here, we report that the mushroom's ( Agaricus bisporus ) stalk has aligned microtubular passages, which shows exceptionally fast capillary effects to draw liquid. After decellularization, the foam has primary component of chitin and maintains the highly parallel microtubules, which endorse exceptionally compressible (90% strain) and injectable to the deep wound, swiftly absorb the blood, elicit clotting by activating blood cells and platelets to promote blood clot formation. The foams' negatively charged surface and fast absorption channels can activate the intrinsic coagulation pathway and non-clotting factor dependent pathway to promote immediate fibrin growth. The hydrophilicity improves the adhesion of the platelets and blood cells, forming firm clotting. The channelled and high compressible foams show great hemostatic performances in vitro blood and in vivo livers and hearts.

CAS / MDL: 62-31-7
研究领域: 生物材料 · 止血 · 生物医学工程 · 组织工程
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MATERIALS & DESIGN · 2022 · IF 9.417

Preparation and hemostatic mechanism of bioactive glass-based membrane-like structure camouflage composite particles

Caiyun Zheng,Jinxi Liu,Que Bai,Yanxiao Quan,Zihao Li,Wenting Chen,Qian Gao,Yanni Zhang,Tingli Lu

Powder hemostatic particles have no limitation on wound type and a wide application prospect in the treatment of wound hemostasis. In this study, bioactive glass-based membrane-like structure camouflage composite particles ( [email protected] /CS) were prepared by Layer-by-layer (LBL) method to coat bovine serum albumin (BSA) and chitosan (CS) on the surface of the synthesized macroporous and mesoporous bioactive glass (MBG). The results showed that [email protected] /CS particles significantly improved the coagulation effect of MBG and could activated both endogenous and exogenous physiological coagulation pathways. [email protected] /CS had the excellent water absorption quality and could immediately release Ca 2+ to participate in the coagulation pathway. The main hemostatic mechanism of [email protected] /CS was that the membrane-like of BSA/CS could form a fibrin network by aggregating erythrocytes and activating platelets, thus rapidly aggregating coagulation factors. In addition, [email protected] /CS particles had a significant hemostatic effect on surface bleeding (tail-amputation model) and internal bleeding (liver injury model) in SD rats, which could shorten the bleeding time and reduce the amount of blood loss effectively. This research work stated that the MBG-based membrane-like structure camouflage composite particles might be with the potential applications as a hemostasis biomaterial for the emergency bleeding.

CAS / MDL: 9048-46-8 70694-72-3
研究领域: 材料科学 · 生物医学工程 · 止血 · 生物材料
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