Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Department of Mechanical Engineering, University of Manitoba, 75 Chancellors Circle, Winnipeg, MB, R3T 5V6, Canada.
Adv Healthc Mater. 2023 Dec;12(30):e2300708. doi: 10.1002/adhm.202300708. Epub 2023 Jul 23.
Hemostatic sealant is required to deal with blood loss, especially in the scenario of traumatic brain injury (TBI), which presents high rates of morbidity and disability. Hemostasis in surgery with traditional gelatin-based sealants often leads to blood loss and other issues in brain because of the hydrophilic gelatin swelling. Herein, hydrophobic effects on the hemostasis in TBI surgery are studied by tuning the chain length of polystyrene (PS) onto methylacrylated gelatin (Gel-MA). The hydrophobicity and hemostatic efficiency can be tuned by controlling the length of PS groups. The platelet activation of modified sealants Gel-MA-2P, Gel-MA-P, and Gel-MA-0.5P is as much as 17.5, 9.1, and 2.1 times higher than Gel-MA in vitro. The hemostatic time of Gel-MA-2P, Gel-MA-P, and Gel-MA-0.5P groups is 2.0-, 1.6-, and 1.1-folds faster than that in Gel-MA group in TBI mice. Increased formation of fibrins and platelet aggregation can also be observed in vitro by scanning electron microscopy. Animal's mortality is lowered by 46%, neurologic deficiency is reduced by 1.5 times, and brain edema is attenuated by 10%. Protein expression is further investigated to exhibit toxic iron-related processes caused by delayed hemostasis and activation of platelets via PI3K/PKC-α signaling. The hydrophobic Gel-MA has the potential in hemostatic TBI and promotes nervous system recovery in brain with the potentials in clinics.
止血剂是处理失血的必要手段,尤其是在创伤性脑损伤(TBI)的情况下,TBI 发病率和致残率都很高。由于亲水性明胶的肿胀,传统的基于明胶的止血剂在手术中的止血常常导致大脑失血和其他问题。本研究通过调整聚苯乙烯(PS)的链长来研究 TBI 手术中的疏水性对止血的影响,使其接枝到甲基丙烯酰化明胶(Gel-MA)上。通过控制 PS 基团的长度,可以调整疏水性和止血效率。改性密封剂 Gel-MA-2P、Gel-MA-P 和 Gel-MA-0.5P 的血小板激活程度分别比 Gel-MA 体外高 17.5、9.1 和 2.1 倍。Gel-MA-2P、Gel-MA-P 和 Gel-MA-0.5P 组的止血时间比 Gel-MA 组在 TBI 小鼠中分别快 2.0、1.6 和 1.1 倍。通过扫描电子显微镜还可以观察到体外纤维蛋白形成和血小板聚集的增加。动物死亡率降低了 46%,神经功能缺损减少了 1.5 倍,脑水肿减轻了 10%。进一步的蛋白质表达研究表明,通过 PI3K/PKC-α 信号通路导致止血延迟和血小板激活,会引起有毒的铁相关过程。疏水性 Gel-MA 具有在 TBI 中止血的潜力,并通过在临床中的潜力促进大脑神经系统的恢复。