Preparation of nanocomposites based on polyacrylic acid and their embolic properties for postpartum hemorrhage
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摘要: 产后出血(Postpartum hemorrhag, PPH)是一种严重的产科并发症，死亡率占所有产科并发症的25%。经导管动脉栓塞术( Transcatheter Arterial Embolization, TAE)已被证明能快速有效地控制顽固性产后出血。明胶海绵颗粒栓塞剂(Gelatin)作为PPH常用的介入栓塞剂，但往往很难成功地完全阻塞受伤的血管，因此在控制活动性出血如假性动脉瘤的表现不尽人意。由聚丙烯酸(Polyacrylic acid, PAA)、二维层状双氢氧化物(Layered double hydroxide, LDH)和聚乙二醇(Polyethylene glycol, PEG200)为原料的液体栓塞剂(PAA-LDH@PEG200)遇水可迅速固化形成水凝胶实现血管完全地闭塞。在体外闭塞模型中，该纳米复合材料PAA-LDH@PEG200在不同直径的管道中移位压力最高达150 kPa，远高于Gelatin闭塞导致的移位压力。此外，PAA-LDH@PEG200表现出良好的生物相容性和体内外可生物降解性。结果表明，所制备的液体栓塞剂有望替代明胶海绵颗粒成为产后大出血治疗的新一代栓塞剂。Abstract: Postpartum hemorrhage (PPH) is a significant obstetric complication, representing 25% of all obstetric complications. Transcatheter Arterial Embolization (TAE) has been proven to be a rapid and effective method for controlling intractable postpartum hemorrhage. Gelatin sponge embolic agent (Gelatin) is a commonly used interventional embolic agent for PPH. However, it is often challenging to completely block the injured blood vessel, which can lead to inadequate control of active bleeding, such as pseudoaneurysms. The liquid embolic agent (PAA-LDH@PEG200), which comprises polyacrylic acid (PAA), two-dimensional layered double hydroxide (LDH), and Polyethylene glycol 200 (PEG200), can rapidly solidify into a hydrogel to achieve complete vascular occlusion. In the in vitro occlusion model, the nanocomposite PAA-LDH@PEG200 exhibits a displacement pressure of up to 150 kPa in pipes of varying diameters, significantly surpassing the pressure caused by Gelatin occlusion. In addition, PAA-LDH@PEG200 has shown good biocompatibility and biodegradability in vivo and in vitro. The results indicate that the developed liquid embolic agent is poised to replace gelatin sponge particles as a next-generation embolic agent for treating postpartum hemorrhage.
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图 1 (a) 聚丙烯酸-二维层状双氢氧化物@聚乙二醇(PAA-LDH@PEG200)的制备；(b) 产后大出血的栓塞性能研究
Figure 1. (a) Preparation of Polyacrylic acid- Layered double hydroxide@Polyethylene glycol (PAA-LDH@PEG200); (b) Embolization performance study of postpartum hemorrhage
图 2 (a) LDH的SEM图；(b) 粒径和zeta电位分布图；(c) 元素Mapping图
Figure 2. (a) SEM image of LDH; (b) Particle size and Zeta potential distribution; (c) Mapping of elements
图 3 (a)PAA和LDH不同质量比例的粘附强度；(b)应力应变
Figure 3. (a) Adhesion strength of PAA and LDH with different mass ratios; (b) Stress and strain
图 4 水凝胶SEM图像：(a) PAA；(b) PAA-LDH；(c) PAA-LDH@PEG200
Figure 4. SEM images of hydrogels: (a) PAA; (b) PAA-LDH; (c) PAA-LDH@PEG200
图 5 (a) 体外闭塞装置图；(b) PAA-LDH和PEG200不同质量比筛选
Figure 5. (a) External block device diagram; (b) Screening of different mass ratios of PAA-LDH and PEG200
图 6 Gelatin和PAA-LDH@PEG200在体外闭塞模型中的压力曲线
Figure 6. Pressure profiles of Gelatin and PAA-LDH@PEG200 in an in vitro occlusion model
图 7 Gelatin和PAA-LDH@PEG200粘附的SEM图：(a)红细胞；(b)血小板
Figure 7. SEM images of Gelatin and PAA-LDH@PEG200 adhesion: (a) Erythrocytes; (b) Platelets
图 8 PAA-LDH@PEG200的HUVEC细胞毒性和血液相容性：(a) HUVEC细胞24 h的AM/PI染色图；(b) HUVEC细胞48 h的AM/PI染色图；(c) HUVEC细胞24 h和48 h的存活率；(d)溶血率
Figure 8. HUVEC cytotoxicity and hemocompatibility of PAA-LDH@PEG200: (a) AM/PI staining plots of HUVEC cells at 24 h; (b) AM/PI staining plots of HUVEC cells at 48 h; (c) HUVEC cell survival at 24 h and 48 h; (d) hemolysis rate
图 9 PAA-LDH@PEG200的体内外降解情况：(a) PAA-LDH@PEG200在小鼠体内不同时间内的降解照片；(b) PAA-LDH@PEG200在体内不同时间的重量；(c) PAA-LDH@PEG200在体外的降解曲线
Figure 9. PAA-LDH@PEG200 degradation in vivo and in vitro: (a) Photos of PAA-LDH@PEG200 degradation at different time in mice; (b) the weight of PAA-LDH@PEG200 in the body at different times; (c) In vitro degradation curve of PAA-LDH@PEG200
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