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生物质及生物质相关止血材料的研究进展

敖青 张戈 丁功涛 王子凡 TeowYeit Haan SajabMohd Shaiful 马忠仁 赵蕾

敖青, 张戈, 丁功涛, 等. 生物质及生物质相关止血材料的研究进展[J]. 复合材料学报, 2024, 42(0): 1-15.
引用本文: 敖青, 张戈, 丁功涛, 等. 生物质及生物质相关止血材料的研究进展[J]. 复合材料学报, 2024, 42(0): 1-15.
AO Qing, ZHANG Ge, DING Gongtao, et al. Research progress on biomass and biomass-related hemostatic materials[J]. Acta Materiae Compositae Sinica.
Citation: AO Qing, ZHANG Ge, DING Gongtao, et al. Research progress on biomass and biomass-related hemostatic materials[J]. Acta Materiae Compositae Sinica.

生物质及生物质相关止血材料的研究进展

基金项目: 国家自然青年科学基金(22104045);甘肃省自然科学基金(23JRRA1733, 23JRRA718)
详细信息
    通讯作者:

    赵蕾,博士,讲师,硕士生导师,主要研究方向为微流控技术辅助制备生物纳米材料 E-mail: zhaolei@xbmu.edu.cn

  • 中图分类号: O636.9; TB332

Research progress on biomass and biomass-related hemostatic materials

Funds: National Natural Science Foundation of China (22104045); Natural Science Foundation of Gansu Province (23JRRA1733, 23JRRA718)
  • 摘要: 伤口的快速止血和愈合对于解决意外事故造成的出血具有重要意义,相关止血材料的开发和应用一直备受关注。以角蛋白、丝素蛋白、胶原蛋白为代表的蛋白类和以纤维素、壳聚糖、海藻酸为代表的多糖类等生物质材料,因其无毒性、低抗原性、良好的生物相容性、生物可降解性等优点在止血领域展现了前所未有的应用价值。基于此,本文对生物质止血材料的设计、制备及止血应用的最新研究进展进行了全面综述,并对其发展前景做了展望,以期为新型高效止血材料的开发和实际应用提供思路。

     

  • 图  1  生物质止血材料

    Figure  1.  Biomass hemostatic materials

    图  2  (a) 截尾后给予SF-BGE、SFBGE/TA和SF-BGE/TA/ZnO水凝胶后失血的照片。(b) 对照组、SF-BGE、SF-BGE/TA、SF-BGE/TA、SF-BGE/TA/氧化锌水凝胶致伤大鼠的失血量 (Mg)。结果报告为平均值±标准差 (n=3)。统计学处理采用单因素方差分析和Tukey‘s后置检验 (*p < 0.05,**p < 0.01)。[48]

    Figure  2.  (a) Photographs of blood loss after tail amputation and administration of SF-BGE, SFBGE/TA and SF-BGE/TA/ZnO hydrogel. (b) Blood loss (mg) from injury rat tail of control, SF-BGE, SF-BGE/TA, and SF-BGE/TA/ZnO hydrogel. The results are reported as the mean ±standard deviation (n = 3). Statistical significance was analyzed by one-way ANOVA and Tukey’s post hoc test (* p < 0.05, ** p < 0.01).

    图  3  兔耳动脉和肝脏损伤模型中不同膜片的出血量。PCLColI (A-D)组与Coli组之间的统计学意义分别为*p < 0.005,**p < 0.05。[57]

    Figure  3.  The amount of bleeding of different films in injury models of rabbit ear artery and liver. Statistical significances between PCLColI (A–D) groups and ColI are denoted as *p < 0.05, **p < 0.005.[57]

    图  4  (a) 大鼠断尾模型的止血时间。(b) 大鼠肝撕裂伤模型止血时间。(c) 大鼠断尾和肝撕裂模型的数字图像。将CSMS-K3涂于 (A) 尾部切割处和 (B) 肝撕裂伤处;涂抹CSMS-K3 5 min后 (C) 大鼠尾部切割处和 (D) 肝撕裂伤处。伤处形成暗红色血块,出血停止。[85]

    Figure  4.  (a) Hemostasis time in rat tail amputation model. (b) Hemostasis time in rat liver laceration model. (c) Digital images of rat tail amputation and liver laceration models. CSMS-K3 was applied onto (A) the tail cut and (B) on the liver injury; 5 min after application on the (C) rat tail cut and (D) the liver laceration. Dark-red blood clot was formed on the injured sites, bleeding stopped.[85]

    图  5  纯海藻酸微球、Alg/Ag NPs、PGA/Alg/Ag NPs和PGA/Alg复合微球的止血分析。(a). 血浆凝血性能,(b). 凝血时间,(c). 凝血图像,(d). PGA/Alg/AgNPs微球的止血示意图

    注:图5d (1) 止血剂提供外源性凝血成分,加速伤口血液凝结;(2) 止血剂促进红细胞、凝血因子、血小板聚集,加速凝血;(3) 止血剂吸收血液中水分,增加血细胞、血小板、凝血因子浓度,阻断创面,促进聚集止血。[93]

    Figure  5.  Hemostasis assays of pure alginate microspheres, Alg/Ag NPs, PGA/Alg/Ag NPs, and PGA/Alg composite microspheres. (a). blood plasma clotting performance, (b). clotting blood time, (c). coagulation images, (d). Schematic hemostasis of PGA/Alg/Ag NPs microspheres

    Note: in Fig 5d (1) The hemostatic agent provides extrinsic coagulation components to accelerate blood clotting on the wound, (2) The hemostatic agent promotes the aggregation of red blood cells, coagulation factors and platelets, and accelerates the coagulation, (3) The hemostatic agent absorbs water in the blood, increases the concentration of blood cells, platelets, and coagulation factors, block the wound area and promotes the aggregation and hemostasis.[93]

    表  1  现有商品化生物质止血材料

    Table  1.   Existing commercial biomass hemostatic materials

    Hemostatic material Product name Manufacturer Mechanism of hemostasis Hemostatic effect Limitations or deficiencies References
    Fibrin sealant Tisseel Baxter Simulates the coagulation process in the body and quickly forms blood clots Complete hemostasis was achieved within 30 s (Arterial bypass) to 6 min (Carotid endarterectomy) The price is expensive, and the cost of transportation and storage is high; It is contraindicated in patients with bovine allergies, who have adverse effects including rash, coagulation disorders, anaphylaxis, and death from premade antibodies [16, 17]
    Evicel Ethicon
    Beriplast P CSL Behring
    Oxidized Cellulose Surgicel Johnson Immediately after the material encounters blood, the fluid in the blood is extracted and blood proteins, platelets, red blood cells and other active components are captured, resulting in an increased concentration of coagulation factors and an accelerated coagulation process Hemostasis is usually successful within 5 min (open surgery) Foreign body reactions, minor postoperative complications, as foci of infection or anaphylaxis, manifested mainly by acute dermatitis, eczema, and serous tumors [9, 18]
    Cutanplast B. Braun
    Surgicel Ethicon
    Gelatin Sponges Gelfoam Pfizer Attaches to the bleeding site, allowing platelets to stay in uniform pores, activating the coagulation cascade Hemostasis was successfully achieved within 5 min (reoperative cardiac surgery or emergency resternotomy) Inability to pack bleeding, and the possibility of breaking the clot when the sponge is removed; It may cause thrombosis of small blood vessels or an inflammatory reaction [17, 19]

    Gelfoam

    Baxter
    Microporous Polysaccharides Arista AH Starch Medical It concentrates blood solids by absorbing water and low-molecular-weight compounds from the blood, thereby providing hemostasis and providing a scaffold for the formation of fibrin clots Haemostasis was completed at 1 min30 s (5 mm pork kidney incision) to 3 min20 s (12 mm pork kidney incision). There will be a slight inflammatory reaction at the beginning of use [20-22]
    Chitosan sponge HemCon HemCon Medical Technologies Positively charged chitosan binds to negatively charged red blood cells. As a result, it leads to the formation of sticky clots to promote hemostasis Complete hemostasis usually occurs within 2 min (Tooth extraction surgery) For limb injuries, tourniquets are required [23, 24]
    ChitoGauze PRO HemCon Medical Technologies
    Celox Z-Medica
    下载: 导出CSV

    表  2  蛋白类止血材料的材料类型、体内模型和止血效果

    Table  2.   Material types, in vivo models, and hemostatic effects of protein-based hemostatic materials

    Hemostatic material Type of material Model of hemostasis Hemostatic effect
    Keratin Injectable hydrogel[34] Mouse model of liver injury Occlusion hemostasis was achieved in 90 s
    Nanoparticles[35] Rat model of liver injury and tail docking The hemostasis time was 60 s and 90 s
    Silk fibroin Composite sponge[47] Mouse model of liver injury 2 min 30 s to completely stop bleeding
    Nanocomposite hydrogels[48] Rat tail docking model The blood loss was only 183.4 ± 50.1 mg
    Collagen Porous sponges[56] Rat tail docking model Complete hemostasis in 5 min 20 s
    Nanofiber membranes[57] Rabbit ear artery, liver injury model The hemostasis time was 95.34 ± 10.05 s and 67.05 ± 7.15 s
    Self-healing hydrogel[58] Mouse hemorrhagic liver model The blood loss was only 0.4 ± 0.15 g
    下载: 导出CSV

    表  3  多糖类止血材料的材料类型、体内模型和止血效果

    Table  3.   Material types, in vivo models, and hemostatic effects of polysaccharide hemostatic materials

    Hemostatic materialType of materialModel of hemostasisHemostatic effect
    CelluloseComposite sponge [67]Rat tail docking and liver injury modelThe blood loss was 159.46 mg and 80.44 mg
    Nanocomposite fibers [70]Lemonified human plasma, lemonified bovine whole bloodThe coagulation time was 143 ± 19 s and 67 ± 5 s
    ChitosanPowder [83]Mouse tail docking modelThe hemostasis time was 158 s, and the blood loss was only 11.0 mg
    Composite microspheres [85]A model of tail docking and liver laceration in ratsThe hemostasis time is 134 s and 99 s
    Composite hydrogel [86]Rat model of liver injury and femoral artery injuryThe hemostasis time was 53 ± 3 s and 189 ± 9 s
    Alginic acidComposite porous microspheres [91]Rat model of liver laceration and tail breakageThe hemostasis time was 73 ± 5 s and 134 ± 5 s
    Foam [94]Porcine liver injury modelThe hemostasis time is 5 min
    StarchSuperabsorbent
    hydrogel [101]
    Rat model of femoral artery injuryThe hemostasis time < 10 s
    Powder [103]Rabbit model of ear vein, dorsal, femoral artery, liver injuryThe hemostasis time was 52 s, 46 s, 122 s and 102 s
    Drug-loaded microporous powder [105]Rabbit ear artery, liver injury modelThe hemostasis time is 108 ± 5 s and 120 ± 6 s
    Hyaluronic acidSponge [113]Mouse model of liver injuryThe hemostasis time was < 60 s, and the blood loss was only 23.2 mg
    Cryogel [114]Rat model of liver injuryThe hemostasis time is 72 s
    下载: 导出CSV
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  • 收稿日期:  2024-05-10
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