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

生物质及生物质相关止血材料的研究进展

1.
西北民族大学　生物医学研究中心, 兰州 730030
2.
马来西亚国立大学　工程与建筑环境学院, 马来西亚雪兰莪州万宜镇 43600

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
计量
- 文章访问数: 47
- HTML全文浏览量: 25
- 被引次数: 0
出版历程
- 收稿日期: 2024-05-10
- 修回日期: 2024-06-19
- 录用日期: 2024-06-28
- 网络出版日期: 2024-07-08

Research progress on biomass and biomass-related hemostatic materials

1.
Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, China
2.
Faculty of Engineering and Built Environment, The National University of Malaysia, Bangi 43600, Selangor Darul Ehsan, Malaysia

Funds: National Natural Science Foundation of China (22104045); Natural Science Foundation of Gansu Province (23JRRA1733, 23JRRA718)

摘要

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。
- 生物质材料 /
- 蛋白质 /
- 多糖 /
- 止血性能 /
- 伤口止血
Abstract: The rapid hemostasis and healing of wounds after trauma hold great significance to solve the bleeding caused by accidents. Therefore, the development and application of related hemostatic materials have attracted much attention. Biomass-derived materials such as proteins including keratin, silk fibroin, collagen and polysaccharides including cellulose, chitosan, and alginic acid are favored by researchers because of their non-toxicity, low antigenicity, good biocompatibility, and biodegradability, and have shown unprecedented application value in the field of hemostasis. In this paper, the latest research results on the design, the preparation and the application of biomass hemostatic materials are comprehensively reviewed, and their development prospects are prospected, which will provide ideas for the development and practical application of new high-efficiency hemostatic materials.
- biomass materials /
- protein /
- polysaccharide /
- hemostasis properties /
- wound hemostasis

HTML全文

图 1 生物质止血材料

Figure 1. Biomass hemostatic materials

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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).

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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]

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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]

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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]

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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]
Gelatin Sponges	Gelfoam	Baxter				[17, 19]
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

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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
Keratin	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
Silk fibroin	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

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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 material	Type of material	Model of hemostasis	Hemostatic effect
Cellulose	Composite sponge ^[67]	Rat tail docking and liver injury model	The blood loss was 159.46 mg and 80.44 mg
Cellulose	Nanocomposite fibers ^[70]	Lemonified human plasma, lemonified bovine whole blood	The coagulation time was 143 ± 19 s and 67 ± 5 s
Chitosan	Powder ^[83]	Mouse tail docking model	The 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 rats	The hemostasis time is 134 s and 99 s
	Composite hydrogel ^[86]	Rat model of liver injury and femoral artery injury	The hemostasis time was 53 ± 3 s and 189 ± 9 s
Alginic acid	Composite porous microspheres ^[91]	Rat model of liver laceration and tail breakage	The hemostasis time was 73 ± 5 s and 134 ± 5 s
Alginic acid	Foam ^[94]	Porcine liver injury model	The hemostasis time is 5 min
Starch	Superabsorbent hydrogel ^[101]	Rat model of femoral artery injury	The hemostasis time < 10 s
	Powder ^[103]	Rabbit model of ear vein, dorsal, femoral artery, liver injury	The hemostasis time was 52 s, 46 s, 122 s and 102 s
	Drug-loaded microporous powder ^[105]	Rabbit ear artery, liver injury model	The hemostasis time is 108 ± 5 s and 120 ± 6 s
Hyaluronic acid	Sponge ^[113]	Mouse model of liver injury	The hemostasis time was < 60 s, and the blood loss was only 23.2 mg
Hyaluronic acid	Cryogel ^[114]	Rat model of liver injury	The hemostasis time is 72 s

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