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Bioactive Materials · 2022 · IF 16.874

Microcluster colloidosomes for hemostat delivery into complex wounds: A platform inspired by the attack action of torpedoes

Bitao Lu,Enling Hu,Ruiqi Xie,Kun Yu,Fei Lu,Rong Bao,Chenhui Wang,Guangqian Lan,Fangyin Dai

Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature, thereby causing massive blood loss and significantly increased mortality. Inspired by the attack action of torpedoes, we synthesized microcluster (MC) colloidosomes equipped with magnetic-mediated navigation and “blast” systems to deliver hemostats into the cavity of vase-type wounds. CaCO 3 /Fe 2 O 3 (CF) microparticles functionalized with Arg-Gly-Asp (RGD) modified polyelectrolyte multilayers were co-assembled with oppositely charged zwitterionic carbon dots (CDs) to form MC colloidosomes, which were loaded with thrombin and protonated tranexamic acid (TXA-NH 3 + ). The composite microparticles moved against blood flow under magnetic mediation and simultaneously disassembled for the burst release of thrombin stimulated by TXA-NH 3 + . The CO 2 bubbles generated during disassembly produced a “blast” that propelled thrombin into the wound cavity. Severe bleeding in a vase-type hemorrhage model in the rabbit liver was rapidly controlled within ∼60 s. Furthermore, in vivo subcutaneous muscle and liver implantation models demonstrated excellent biodegradability of MC colloidosomes. This study is the first to propose a novel strategy based on the principle of torpedoes for transporting hemostats into vase-type wounds to achieve rapid hemostasis, creating a new paradigm for combating trauma treatment.

研究领域: 生物医学工程 · 材料科学 · 止血 · 伤口愈合
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CARBOHYDRATE POLYMERS · 2024 · IF 10.7

Dialdehyde starch cross-linked aminated gelatin sponges with excellent hemostatic performance and biocompatibility

Yu-He Zhu,Chen-Yu Zhou,Xu Peng,Wei Wang,Zhuang Liu,Rui Xie,Da-Wei Pan,Xiao-Jie Ju,Liang-Yin Chu

Developing a hemostatic material suitable for rapid hemostasis remains a challenge. This study presents a novel aminated gelatin sponge cross-linked with dialdehyde starch, exhibiting excellent biocompatibility and hemostatic ability. This aminated gelatin sponge features hydrophilic surface and rich porous structure with a porosity of up to 80 %. The results show that the aminated gelatin sponges exhibit superior liquid absorption capacity and can absorb up to 30–50 times their own mass of simulated body fluid within 5 min. Compared with the commercial gelatin hemostatic sponge and non-aminated gelatin hemostatic sponge, the aminated gelatin hemostatic sponge can accelerate the hemostatic process through electrostatic interactions, demonstrating superior hemostatic performance in both in vitro and in vivo hemostasis tests. The aminated gelatin sponge can effectively control the hemostatic time within 80 s in the in vivo rat femoral artery injury model, significantly outperforming both commercial and non-aminated gelatin sponges. In addition, the aminated gelatin sponge also exhibits good biocompatibility and certain antibacterial properties. The proposed aminated gelatin sponge has very good application prospects for the management of massive hemorrhage.

研究领域: 生物材料 · 止血 · 生物医学工程 · 组织工程
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CELLULOSE · 2020 ·Vol. 27 ·期 6 ·3443-3453 · IF 4.21

Facile fabrication of carboxymethyl chitosan/paraffin coated carboxymethylated cotton fabric with asymmetric wettability for hemostatic wound dressing

Wang Yamei,Xiao Dongdong,Zhong Yi,Zhang Linping,Chen Zhize,Sui Xiaofeng,Wang Bijia,Feng Xueling,Xu Hong,Mao Zhiping

Abstract Achieving effective hemostasis is significant to ensure the survival of the people with acute massive bleeding in the battlefield or daily life in pre-hospital care. In this work, modified cotton fabric with asymmetric wettability (Janus) was prepared using a fast and simple spray-coating strategy, where, one side of the fabric was sprayed with carboxymethyl chitosan solution to achieve hydrophilicity (0°) while the other side with hydrophobicity (152°) was built using paraffin. The hydrophilic surface could provide blood absorption and promote hemostasis, while the hydrophobic surface prevented the excessive blood absorption. The hemostatic efficiency of fabrics was tested in vitro and in vivo. Here, the carboxymethyl chitosan coated carboxymethylated cotton (CS-MCF) and Janus showed better hemostatic capacity than the cotton fabric (CF) in vitro with the lower blood clotting index. Furthermore, the Janus had better hemostatic performance than CF in rat liver animal model, and prolonged the survival time of the rats in carotid artery animal model. Therefore, Janus, with superior hemostatic efficiency over the cotton fabric, has a bright application prospect as hemostatic wound dressing. Graphic abstract

研究领域: 材料科学 · 生物医学工程 · 伤口护理 · 止血
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Nature Communications · 2024 ·Vol. 15 ·期 1 ·1-14 · IF 14.7

Neutrophil extracellular traps-inspired DNA hydrogel for wound hemostatic adjuvant

Ye Rui,Zhu Ziyu,Gu Tianyi,Cao Dengjie,Jiang Kai,Dai Qiang,Xing Kuoran,Jiang Yifan,Zhou Siyi,Cai Ping,Leong David Tai,Yu Mengfei,Song Jie

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.

研究领域: 生物材料 · 止血 · 组织工程 · 伤口愈合
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Acta Biomaterialia · 2021 · IF 8.947

Chitosan-based multifunctional flexible hemostatic bio-hydrogel

Fuyu Song,Yue Kong,Changyou Shao,Yi Cheng,Jie Lu,Yehan Tao,Jian Du,Haisong Wang

Realizing the potential application of chitosan as an effective biomedical hemostatic agent has become an emerging research hotspot. However, fabricating a flexible chitosan-based hemostatic bio-hydrogel with self-adhesion feature in humid conditions and rapid hemostasis capability remains a challenge. Herein, we reported the development of chitosan-based hydrogels (DCS-PEGSH gels) with typical multilevel pore structures , which were cross-linked by 3-(3,4-dihydroxyphenyl) propionic acid-modified chitosan (DCS) and sebacic acid-terminated polyethylene glycol modified by p-hydroxybenzaldehyde (PEGSH). By precisely regulating the proportion of PEGSH, the fabricated bio-hydrogels displayed favorable cytocompatibility, suitable stretchability (∼780%), and blood absorbability (1300% ± 50%). Moreover, the strong adhesion (∼68.5 kPa) of the assembled bio-hydrogel ensured its firm adherence on pigskin and on bleeding wound in both static and dynamic humid environments without shedding, thus providing a long service life. The fabricated hydrogels exhibited shorter blood clotting time (50 s) and lower blood clotting index (BCI, 41) than the commercial chitosan sponge (288 s, BCI 65). Notably, the amount of blood loss from the liver in mice was reduced by almost 90% as compared to that for the control group. This study paves a solid way for developing a chitosan-based hydrogel with self-adhesive, self-healing, stretchability, biocompatibility, and antibacterial and antioxidant properties through molecular design and structural regulation, which will enable the biomedical application of chitosan in emergency hemostasis, particularly in joints and extremities. Statement of significance The design and preparation of multifunctional integrated green adhesive bio-hydrogels while avoiding the use of organic solvents and toxic chemical reagents has been an emerging challenge. Herein, a flexible chitosan-based hemostatic bio-hydrogel that integrates multifunctional properties was successfully synthesized. The bio-hydrogel displayed suitable stretchability (780%) and blood absorbability (1300% ± 50%). Moreover, the strong adhesion (68.5 kPa) ensured firm adherence of the assembled hydrogel on pigskin and on the bleeding wound site in both static and dynamic humid environments without shedding, thus providing a long service life. In addition, the designed hydrogel showed good compatibility and antibacterial performance. The dynamic Schiff base endowed the bio-hydrogel with excellent self-healing performance without any external stimuli.

研究领域: 生物医学工程 · 材料科学 · 组织工程 · 止血
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Journal of Materials Chemistry B · 2023 ·Vol. 11 ·期 42 ·10234-10251 · IF 7

Wool keratin/zeolitic imidazolate framework-8 composite shape memory sponge with synergistic hemostatic performance for rapid hemorrhage control

Feng Sang,Xiao Yang,Jiahui Hao,Yuzhen Wang,Xiaoqin Si,Xujian Li,Luqi Pan,Zhaipu Ma,Changcan Shi

Uncontrollable hemorrhage and subsequent wound infection pose severe threats to life, especially in the case of deep, non-compressible, massive bleeding. Here, a wool keratin/zeolitic imidazolate framework-8 (WK/ZIF-8) composite shape memory sponge is prepared by incorporating ZIF-8 nanoparticles into wool keratin. The combination of keratin and ZIF-8 particles not only reduces the effect of ZIF-8 particles on cell viability but also bolsters the mechanical properties of the keratin sponge and endows it with antibacterial efficacy. Due to the synergistic effect of the excellent hemostatic performance of keratin and Zn2+ release from ZIF-8 nanoparticles, the porous structure suitable for blood cell adhesion and the shape recovery ability of sponges, the WK/ZIF-8 composite sponge exhibits superior hemostatic performance to commercial medical sponges in SD rat and rabbit hemorrhage models. In addition, in vitro and in vivo antibacterial experiments demonstrate the anti-infection activity of the composite sponge. Overall, the WK/ZIF-8 composite sponge provides a promising approach to rapidly control bleeding and promote wound healing.

CAS / MDL: 151-21-3
研究领域: 生物材料 · 止血 · 组织工程 · 伤口愈合 · 纳米技术
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Materials Today Communications · 2024 · IF 3.7

Tannic acid-crosslinked gelatin composite microspheres adsorbed with CQAS or Ca2+ for rapid hemostasis

Guanhua Jiao,Dandan Wei,Liuxin Yang,Yinghua Tao,Min Liang,Li Xu,Pengfei Ren,Tianzhu Zhang,Feiling Feng,Yonghua Li,Hongbin Yuan

In the case of massive blood loss due to natural disasters and wars, timely and rapid hemostasis is of great significance to improve the survival rate of injured people. Nevertheless, uncontrolled, noncompressible, and irregular bleeding wounds remain a giant challenge for rapid hemostasis. In this study, the tannic acid-crosslinked gelatin was first obtained by Michael addition reaction, and then the tannic acid-crosslinked gelatin composite microspheres (TGMs) were prepared by the emulsion cross-linking method. TGMs could significantly improve the water absorption and hemostatic performance compared with single component gelatin microspheres (GMs). Increasing the water absorption ratio and introducing blood coagulation factors into composite materials are simple and effective strategies to enhance the hemostatic properties. Therefore, chitosan quaternary ammonium salt (CQAS) and Ca 2+ were electrostatic adsorbed to obtain two kinds of functional TGMs, which were respectively CQAS-absorbed TGMs (T 2 GMs-CQAS) and calcium ion-absorbed TGMs (T 2 GMs-Ca 2+ ). Notably, T 2 GMs-CQAS, and T 2 GMs-Ca 2+ could absorb water rapidly within 3 seconds, in addition, especially the water absorption ratio of T 2 GMs-CQAS could reach 2.95 times compared with GMs. Benefited from rapid water absorption, coagulation pathway activation, and red blood cells aggregation of T 2 GMs-CQAS and T 2 GMs-Ca 2+ , resulting in rapid blood coagulation in vitro . In addition, CQAS and Ca 2+ provided strong and intrinsic antibacterial activity due to positive charge. Moreover, in the tail amputation and liver hemostatic models, T 2 GMs-CQAS and T 2 GMs-Ca 2+ demonstrated superior hemostatic effects compared to commercial Yunnan Baiyao®. In conclusion, T 2 GMs-CQAS and T 2 GMs-Ca 2+ have potential applications as hemostatic dressings in uncontrolled, noncompressible, and irregular bleeding wounds.

CAS / MDL: 9000-70-8 1401-55-4
研究领域: 生物材料 · 止血 · 伤口愈合 · 材料科学 · 生物医学工程
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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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CARBOHYDRATE POLYMERS · 2024 · IF 10.7

Facile preparation of fatigue-resistant Mxene-reinforced chitosan cryogel for accelerated hemostasis and wound healing

Zhengguo Wu,Shanshan Li,Xiaoqian Qin,Lu Zheng,Jiawei Fang,Lansheng Wei,Changliang Xu,Zhong Alan Li,Xiaoying Wang

The development of highly effective chitosan-based hemostatic materials that can be utilized for deep wound hemostasis remains a considerable challenge. In this study, a hemostatic antibacterial chitosan/N-hydroxyethyl acrylamide (NHEMAA)/Ti 3 C 2 T x (CSNT) composite cryogel was facilely prepared through the physical interactions between the three components and the spontaneous condensation of NHEMAA. Because of the formation of strong crosslinked network, the CSNT cryogel showed a developed pore structure (~ 99.07 %) and superfast water/blood-triggered shape recovery, enabling it to fill the wound after contacting the blood. Its capillary effect, amino groups, negative charges, and affinity with lipid collectively induced rapid hemostasis, which was confirmed by in vitro and in vivo analysis. In addition, CSNT cryogel showed excellent photothermal antibacterial activities, high biosafety, and in vivo wound healing ability. Furthermore, the presence of chitosan effectively prevented the oxidation of MXene, thus enabling the long-term storage of the MXene-reinforced cryogel. Thus, our hemostatic cryogel demonstrates promising potential for clinical application and commercialization, as it combines high resilience, rapid hemostasis, efficient sterilization, long-term storage, and easy mass production.

研究领域: 生物医学材料 · 组织工程 · 再生医学
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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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CARBOHYDRATE POLYMERS · 2022 · IF 10.723

Expandable carboxymethyl chitosan/cellulose nanofiber composite sponge for traumatic hemostasis

Min Zhou,Jiaxing Liao,Guobing Li,Zhijie Yu,Dandan Xie,Huyue Zhou,Fengling Wang,Yukun Ren,Rufu Xu,Yue Dai,Jie Wang,Jingbin Huang,Rong Zhang

Uncontrolled hemorrhage poses a severe life-threatening situation. However, traditional hemostats still have various limitations. It is urgent to develop a material with excellent biocompatibility and hemostatic ability. Evidence has shown that carboxymethyl chitosan (CMCS) has hemostatic properties and good compatibility. Herein, we develop an expandable hemostatic sponge by modifying CMCS with cellulose nanofibrils (CNFs) through the CO-NH cross-linking method. We verified its potential as a hemostatic agent both in vivo and in vitro . The results demonstrated that the prepared carboxymethyl chitosan/cellulose nanofiber composite (CNF-CMCS) sponges could absorb blood, quickly expand to exert pressure in the wound, and exhibit an excellent coagulation ability. The CNF-CMCS sponges significantly decreased the bleeding time and blood loss in several hemorrhage models and possessed a significant advantage in treating the deep penetrating injury hemorrhage. Therefore, the sponges provide a unique application prospect and potential as a penetrating trauma hemostatic agent.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 生物材料 · 止血 · 纳米技术 · 生物医学工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2022 · IF 5.999

Fabrication of microspheres containing coagulation factors by reverse microemulsion method for rapid hemostasis and wound healing

Nan Wang,Shuying Zhao,Xiaoyong Tian,Shanyi Guang,Hongyao Xu

Traditional dressings, such as bandages, gauze, and cotton pads stick to new granulation tissue, thereby aggravating wound injury or causing secondary injury during replacement. Microspheres that are biodegradable and adaptable to various wound shapes are a good alternative to traditional dressings. In this work, a novel microsphere was prepared by reverse microemulsion method using sodium alginate and silk peptide (SP) as the aqueous phase. After cross-linking by Ca 2+ , calcium alginate (CA) and SP composite microspheres called CA/SP were prepared. By adjusting the SP content, the swelling rate of microspheres reached 1050 % and the pore diameter reached 19.59 nm. In addition, the introducing SP provided a stable loading site for thrombin (Th). This platform (called CA/SP@Th)—integrating rapid blood enrichment, calcium release , and Th catalysis—can ensure rapid hemostasis in a variety of bleeding models. Additionally, the SP present in this modality also promoted fibroblast proliferation, this increased the wound closure rate in a total cortex injury mouse model (more than 97 % within 15 days). Therefore, CA/SP@Th can be used as a multifunctional dressing for rapid hemostasis and wound healing.

研究领域: 生物材料 · 医学工程 · 创伤修复
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