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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Rapid hemostatic covered stent with drug-loaded gelatin-alginate/PVDF Janus composite membrane for coronary artery perforation

Yuan Ji,Jichi Zhang,Yijie Liu,Guo Dong,Zaixing Jiang

The implantation of covered stents has significantly contributed much to the rescue treatment of coronary artery perforation (CAP). The ability to achieve rapid hemostasis in cases of severe coronary artery perforation using covered stents alone has so far been elusive. Here, we investigate a Janus composite covered stent for rapid hemostasis in CAP. The covered stent has the dual functions of sealing perforation and rapid hemostasis, which is suitable for the rescue of CAP. This achievement is realized by assembling the tough polyvinylidene fluoride (PVDF) membrane and the drug-loaded hemostatic coating, thereby amalgamating their distinct functionalities. The PVDF membrane served as a physical shield that prevented blood leakage and blocked procoagulant drugs from forming the thrombus in the vessel. Meanwhile, the drug-loaded hemostatic coating, when in contact with the perforation area, swiftly procoagulant. The in vitro cytocompatibility and coagulation property tests demonstrated excellent biocompatibility and hemostatic performance of the Janus composite covered stent. The approach is applicable across almost all sizes of common bare stents in clinical, which has great potential for the rescue of CAP.

研究领域: 心脏病学 · 生物材料 · 止血 · 介入放射学
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

High-strength anti-bacterial composite cryogel for lethal noncompressible hemorrhage hemostasis: Synergistic physical hemostasis and chemical hemostasis

Ying Huang,Xin Zhao,Chunbo Wang,Jueying Chen,Yuqing Liang,Zhenlong Li,Yong Han,Baolin Guo

Porous cryogel with its poor mechanical properties greatly limit its application for lethal non-compressible bleeding from deep wounds. Here, we creatively combined foaming reaction and cryo-polymerization reaction to prepare a series of high-strength composite cryogel hemostatic agents based on Poly(vinyl alcohol) (PVA), Carboxymethyl chitosan (CMCS) and Dopamine (DA) to cope with lethal noncompressible bleeding. The optimized PVA/CMCS-DA6 cryogel (1 mL prepolymer solution contains 6 mg DA) exhibited compression stress higher than 125 kPa at 80% compression strain and tensile stress-at-break higher than 155 kPa which are much higher than that of traditional cryogels. The hemostatic material with shape memory behavior and high compression strength can effectively stop lethal non-compressible bleeding, which has a good physical hemostatic effect, and the hemostat is easy to be removed after hemostasis. In addition, PVA/CMCS-DA6 cryogel showed better whole blood clotting ability, platelets and blood cells activation ability than commercial gelatin sponge and medical gauze, which has a good chemical hemostatic effect. PVA/CMCS-DA6 cryogel with synergistic chemical hemostasis and physical hemostasis showed outstanding hemostatic capacity in the rabbit liver defect non-compressible hemorrhage model and lethal coagulopathic rabbit liver defect bleeding model. Therefore, high-strength PVA/CMCS-DA cryogels have great potential as a new hemostatic agent for controlling lethal bleeding and providing a new idea for the design of efficient hemostatic materials.

CAS / MDL: 62-31-7 50-00-0
研究领域: 生物材料 · 止血 · 生物医学工程 · 材料科学
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ADVANCED FUNCTIONAL MATERIALS · 2023 ·Vol. 33 ·期 36 ·2302793 · IF 19

Microgel Assembly Powder Improves Acute Hemostasis, Antibacterial, and Wound Healing via In Situ Co-Assembly of Erythrocyte and Microgel

Bingrui Li,Haofei Li,Hongjie Chen,Yang Liu,Junlin Chen,Qi Feng,Xiaodong Cao,Hua Dong

Rapid and effective hemostasis on irregular-shaped non-compressible bleeding wounds is still one of the key challenges in clinical practice. Herein, a novel multi-functional microgel assembly powder (MAP) composed of oxidized dextran/methacrylate gelatin (ODex/GelMA) microgel powder and long-chain alkyl quaternized chitosan (LQCS) crosslinker powder is reported for acute hemostasis, antibacterial, and wound healing. When MAP is applied onto bleeding wounds, porous ODex/GelMA microgel powder immediately absorbs massive liquid in blood whilst LQCS induces in situ co-assembly of erythrocytes and microgels. In other words, MAP combines the merits of hemostatic powders and hemostatic hydrogels, that is, the excellent hemostasis performance of MAP is originated from not only the high fluid uptake ratio/rate that causes the aggregation of coagulation factors and erythrocytes, but also the formation of erythrocytes-involved hydrogel-like microgel assembly that dramatically improves the mechanical strength, tissue adhesion and wound sealing performance in blood compared with those in PBS. In addition, MAP also exhibits excellent antibacterial ability, and promotes the wound healing in bacterial-infected full-thickness skin wounds. The fantastic features of MAP including low cost, easy synthesis and usage, excellent hemostasis on irregular-shaped, non-compressible bleeding wounds, outstanding antibacterial and wound healing, good cytocompatibility, make it a promising hemostatic material and wound dressing.

研究领域: 生物医学工程 · 材料科学 · 止血 · 伤口护理 · 组织工程
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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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Gels · 2024 ·Vol. 10 ·期 1 ·68 · IF 5

Hydrogel-Transformable Antioxidant Poly-γ-Glutamic Acid/Polyethyleneimine Hemostatic Powder for Efficient Wound Hemostasis

Xiang Li,Wenli Han,Gao He,Jiahao Yang,Jing Li,Hongxia Ma,Shige Wang

Hemostatic powder, which can absorb large amounts of water and tends to produce repeated hydration with tissue, has been clinically proven as an ideal engineering material for treating wounds and tissues. We herein designed a polypeptide-based hemostatic powder. A water-soluble polypeptide, γ-polyglutamic acid (γ-PGA), was mixed with the polyethyleneimine (PEI), N-hydroxysuccinimide, and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide. The solution of these polymers was lyophilized to harvest the γ-PGA/PEI powder (PP hemostatic powder). When deposited on a bleeding wound, the PP hemostatic powder can quickly absorb a large amount of blood and interstitial fluid, concentrate coagulation factors, coagulate blood cells, and eventually form a stable mechanical hydrogel. The wound bleeding time of the PP hemostatic powder group was 1.8 ± 0.4 min, significantly lower than that of the commercial chitosan hemostatic powder group (2.8 ± 0.4 min). The PP hemostatic powder was endowed with antioxidant capacity by introducing protocatechuic aldehyde, which can effectively inhibit inflammation and promote wound healing. Therefore, via preparation through a facile lyophilization method, the PP hemostatic powder is expected to find a wide application prospect as a qualified hemostatic powder.Keywords:hemostatic powder;hydrogel;γ-polyglutamic acid;polyethyleneimine;wound hemostasis

研究领域: 生物医学工程 · 材料科学 · 药剂学
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BIOMACROMOLECULES · 2023 · IF 6.2

Biomimetic and Multifunctional Hemostatic Hydrogel with Rapid Thermoresponsive Gelation and Robust Wet Adhesion for Emergency Hemostasis: A Rational Design Based on Photo-Cross-Linking Coordinated Hydrophilic–Hydrophobic Balance Strategies

Hongyang Song,Lei Xing,Wentao Liu,Xue Wang,Zhaosheng Hou,Yue Wang,Zhenhao Zhang,Yiming Li,Tianduo Li,Xiaolong Wang,Hui Chen,Shu Xing,Jing Xu

Uncontrolled bleeding in emergency situations is a great threat to both military and civilian lives, and an ideal hemostat for effectively controlling prehospital hemorrhage is urgently needed but still lacking. Although hemostatic hydrogels are promising for emergency hemostasis, they are currently challenged by either the mutual exclusion between a short gelation time and strong adhesive network or the insufficient functionality of ingredients and complicated operations for in situ curing. Herein, an extracellular matrix biopolymer-based and multifunctional hemostatic hydrogel that simultaneously integrates rapid thermoresponsive gelation, robust wet adhesion, and ease of use in emergencies is rationally engineered. This hydrogel can be conveniently used via simple injection and achieves instant sol–gel phase transition at body temperature. Its comprehensive performance could be facilely regulated by tuning the proportions of components, and the optimal performance (gelation time 6–8 s, adhesion strength 125 ± 3.6 kPa, burst pressure 282 ± 4.1 mmHg) is established due to the coordinated enhancement of the photo-cross-linking pretreatment and the hydrophilic–hydrophobic balance among various interactions in the hydrogel system. Additionally, it exhibits significant coagulation effect in vitro and enables effective hemostasis and wound healing in vivo. This work provides a promising platform for versatile applications of hydrogel-based materials, including emergency hemostasis.

研究领域: 生物材料学 · 医学工程 · 创伤急救
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Materials Today Communications · 2022 · IF 3.662

Hemostatic cotton based on biocompatible poly(vinyl alcohol)/soluble starch-fish skin collagen composites

Jiayi Guo,Qun Liu,Jun Cheng,Xin Fu,Yucang Zhang,Huan Yang

Fish skin collagen has attracted a wide range of attention in the field of hemostatic materials due to its excellent biocompatibility and hemostatic performance. In this work, the hemostatic cotton based on poly(vinyl alcohol)/soluble starch-fish skin collagen (PVA/SS-FSC) composites was prepared by solvent displacement followed by lyophilization. The experimental results showed that the PVA/SS enabled the composite material to have 3-D porous structures. When compounding with FSC, PVA/SS-FSC(1) composite cotton (mass ratio 1:1:1) possessed 3-D porous structures, good water absorption, and no cytotoxicity or hemolytic properties. In vitro and in vivo experiments demonstrated that the PVA/SS-FSC(1) hemostatic cotton accelerated the coagulation rate, reduced blood loss, and improved the hemostatic efficiency. Furthermore, arterial hemostasis tests in rats confirmed that the PVA/SS-FSC(1) hemostatic cotton afforded a shorter hemostasis time (64 ± 7 s) and lower blood loss (323 ± 38 mg) compared with commercial hemostatic gauze (210 ± 12 s and 840 ± 41 mg, respectively), thus indicating promising applications in rapid wound hemostasis.

CAS / MDL: 9002-89-5 75-65-0
研究领域: 材料科学 · 生物材料 · 止血 · 生物医学工程
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POLYMERS FOR ADVANCED TECHNOLOGIES · 2023 ·Vol. 34 ·期 5 ·1608-1621 · IF 3.4

Preparation and evaluation of aldehyde starch hemostatic microspheres crosslinked with L-cystine dimethyl ester for ultrarapid rapid hemostasis

Xujian Li,Xumin Chen,Zhixiao Ji,Luqi Pan,Yi Liu,Xiao Yang,Changcan Shi

Rapid hemostasis, biosafety, and adaptability to different bleeding sites are the focus of research on hemostatic materials. In this work, an efficient and simple preparation of aldehyde starch hemostatic microspheres (ASHMs) crosslinked with L-cystine dimethyl ester was developed. Through a series of physicochemical parameters and in vitro and in vivo hemostatic properties measurements, the results showed that under the optimal crosslinking degree, ASHMs had a regular and uniform spherical shape, and it had a liquid suction capacity of up to 880%. At the same time, the aldehyde groups on its surface can increase the adhesion and aggregation of blood cells, thereby enhancing the hemostatic effect, which can be considered as a synergistic effect. More importantly, ASHMs have good biocompatibility and minimal intradermal irritation. Taken together,ASHMs could be used as potential novel hemostatic materials for surgical treatment.

研究领域: 生物材料学 · 医学工程 · 外科治疗
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Nature Communications · 2022 ·Vol. 13 ·期 1 ·1-14 · IF 17.694

Efficient, biosafe and tissue adhesive hemostatic cotton gauze with controlled balance of hydrophilicity and hydrophobicity

He Huaying,Zhou Weikang,Gao Jing,Wang Fan,Wang Shaobing,Fang Yan,Gao Yang,Chen Wei,Zhang Wen,Weng Yunxiang,Wang Zhengchao,Liu Haiqing

Cotton gauze is a widely used topical hemostatic material for bleeding control, but its high blood absorption capacity tends to cause extra blood loss. Therefore, development of rapid hemostatic cotton gauze with less blood loss is of great significance. Here, we develop an efficient hemostatic cotton gauze whose surface is slightly modified with a catechol compound which features a flexible long hydrophobic alkyl chain terminated with a catechol group. Its hemostatic performance in animal injuries is superior to standard cotton gauze and Combat Gauze TM . Its biosafety is similar to cotton gauze and rebleeding hardly occurs when the gauze is removed. Here, we show its hemostatic capability is attributable to the rapid formation of big and thick primary erythrocyte clots, due to its effective controlling of blood movement through blocking effect from tissue adhesion by catechol, blood wicking in cotton, and the hydrophobic effect from long alkyl chains.

研究领域: 生物医学工程 · 材料科学 · 血液学
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Bioactive Materials · 2021 · IF 14.593

Microfluidics-assisted optimization of highly adhesive haemostatic hydrogel coating for arterial puncture

Xingjie Yin,Jingli Ren,Wei Lan,Yu Chen,Mengping Ouyang,Hua Su,Lianbin Zhang,Jintao Zhu,Chun Zhang

Although common in clinical practice, bleeding after tissue puncture may cause serious outcomes, especially in arterial puncture. Herein, gelatin-tannic acid composite hydrogels with varying compositions are prepared, and their adhesive properties are further optimized in microfluidic channel-based simulated vessels for haemostasis in arterial puncture. It is revealed that the composite hydrogels on the syringe needles used for arterial puncture should possess underwater adhesion higher than 4.9 kPa and mechanical strength higher than 86.0 kPa. The needles coated with the gelatin-tannic acid composite hydrogel completely prevent blood loss after both vein and arterial puncture in different animal models. This study holds great significance for the preparation of haemostatic needles for vessel puncture, and gelatin-tannic acid hydrogel coated needles may help to prevent complications associated with arterial puncture.

研究领域: 生物医学工程 · 材料科学 · 止血
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Biomaterials Advances · 2024 · IF 5.5

A facile way to fabricate a thrombin immobilized composite sponge with dual hemostatic effects for acute hemorrhage control

Dandan Hou,Yansen Wang,Liya Qi,Chunyao Wang,Jingqian Deng,Xiaohuan Zhao,Xue Geng,Qiang Sun,Lin Ye,Zifang Guo

Uncontrolled bleeding and excessive blood loss stand as the leading causes of death in complex surgeries, civilian traumas, and military operations. Sponges have been used for developing efficiency hemostats, but most commonly used hemostatic sponges possess only one single coagulation mechanism or lack inherent blood clotting ability. Herein, we proposed simple yet innovative approaches for creating novel hemostatic composite sponges with dual hemostatic effects. Bacterial cellulose (BC) was first introduced into polyvinyl alcohol (PVA) matrix to develop a BC/PVA (CP) sponge featuring a unique cellulose-embedded porous network structure and desirable properties. Subsequently, thrombin was immobilized on CP through an easy method that combines physical adsorption and covalent binding to fabricate thrombin-carrying CP (TCP) composite sponges. The resulting composites boasted a highly porous structure, outstanding liquid-absorption capacity, low hemolysis rate, and superior biocompatibility. In vitro clotting tests revealed that TCP displayed potent coagulation capabilities, a rapid blood absorption rate, and the ability to stimulate and activate blood components along with the coagulation cascade. In vivo hemostatic assessments further confirmed that TCP offered high hemostatic efficiency and multifaceted hemostatic effects, making it suitable for the management of acute and severe bleeding.

CAS / MDL: 9001-60-9
研究领域: 生物材料学 · 医学工程 · 止血材料研究
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Biomaterials Science · 2018 ·Vol. 6 ·期 12 ·3332-3344 · IF 5.831

Evaluation of absorbable hemostatic agents of polyelectrolyte complexes using carboxymethyl starch and chitosan oligosaccharide both in vitro and in vivo

Xingtao Chen,Yonggang Yan,Hong Li,Xuehong Wang,Songchao Tang,Quan Li,Jie Wei,Jiacan Su

Absorbable hemostatic agents with a high hemostatic efficacy play an important role in surgical and severely traumatic hemostasis. In the present study, by applying polyelectrolyte assembly, polyelectrolyte complexes (PECs), using carboxymethyl starch (CMS) and chitosan oligosaccharide (COS), with controllable physicochemical properties were prepared and optimized for hemorrhage control. Particle size, zeta potential, morphology and water absorption of the PECs with different CMS/COS ratios were systematically evaluated. The results of in vitro degradation in PBS suggested that CMS/COS PECs were degradable and their degradation rates, which decreased with the increase of the COS content, were suitable for absorbable hemostatic agents. The in vivo hemostatic efficacy of the PECs with 10 wt% COS content (PEC 10), which was evaluated in a rabbit hepatic hemorrhage model, was better than CMS but decreased with the increase of the COS content. The plasma coagulation evaluation revealed that the PECs could significantly activate and accelerate the coagulation cascade through both the intrinsic and extrinsic pathways but could not directly affect the common pathway. CMS/COS PECs also showed antimicrobial activity against S. aureus, which enhanced with the increase of the COS content, but failed against E. coli. Moreover, PEC 10 displayed excellent cytocompatibility with MC3T3-L1 and good tissue compatibility in a rabbit liver model. These findings not only suggest that CMS/COS PECs with a suitable COS content were promising absorbable hemostatic agents for internal use but they are also useful to understand the underlying principles for designing PEC based hemostatic agents.

研究领域: 生物材料 · 止血学 · 生物医学工程
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