School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Wenzhou Institute of Biomaterials and Engineering, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325011, China.
Wenzhou Institute of Biomaterials and Engineering, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325011, China.
Acta Biomater. 2019 Nov;99:220-235. doi: 10.1016/j.actbio.2019.08.039. Epub 2019 Aug 23.
It is challenging for traditional hemostatic sponges to meet the clinic demand for both uncontrolled and noncompressible hemorrhage. With the aim to develop a rapid shape recovery material with both active and passive hemostatic performance, a dual-functional hemostatic sponge (TRAP-Sp) with a macroporous structure and good mechanical properties for controlling massive and noncompressible hemorrhage was prepared by chemically immobilizing thrombin-receptor-agonist-peptide (TRAP) onto a starch/polyethylene glycol (PEG) sponge. The TRAP2-Sp1 showed the best hemostatic performance among all samples in both rat artery uncontrollable hemorrhage and liver defect noncompressible hemorrhage models. When analyzing the hemostatic mechanism of TRAP-Sp, the high water absorption capacity of the sponge contributed to absorbing plasma, concentrating blood cells, and enhancing blood coagulation. After absorbing water, the shape-fixed TRAP-Sp with sufficient mechanical strength and high resilience can rapidly expand and apply pressure to the wound. TRAP immobilized on the sponge could activate the adhered platelets in an active pathway. Additionally, evaluation of cytotoxicity, hemolysis, and histology further highlighted the adequate biocompatibility of TRAP-Sp. With excellent hemostatic performance and biosafety, this sponge could be a potential candidate as a topical hemostatic agent for uncontrolled and noncompressible hemorrhage. STATEMENT OF SIGNIFICANCE: There is a need for innovative hemostatic materials for both uncontrolled and noncompressible hemorrhage. This manuscript describes a rapid shape recovery hemostatic sponge with both active and passive hemostatic performances synthesized by foaming technique, cross-linking reaction, and chemical immobilization of thrombin-receptor-agonist-peptide (TRAP). On contact with blood, the shape-fixed sponge can not only rapidly recover its original shape and concentrate platelets and RBCs but also activate the adhered platelets efficiently. The dual-functional sponge has excellent hemostatic efficacy in rat femoral artery hemorrhage and can control noncompressible hemorrhage in penetrating liver wound. Thus, we believe that this sponge could be a potential candidate as a topical hemostatic agent for uncontrolled and noncompressible hemorrhage.
对于传统的止血海绵来说，要同时满足失控性出血和非压迫性出血的临床需求具有挑战性。为了开发一种具有主动和被动止血性能的快速形状恢复材料，本研究通过化学固定将凝血酶受体激动肽（TRAP）固定到淀粉/聚乙二醇（PEG）海绵上，制备了一种具有大孔结构和良好机械性能的双重功能止血海绵（TRAP-Sp），用于控制大量非压迫性出血。在大鼠股动脉失控性出血和肝脏穿透性损伤非压迫性出血模型中，TRAP2-Sp1 显示出所有样品中最好的止血性能。在分析 TRAP-Sp 的止血机制时，海绵的高吸水性有助于吸收血浆、浓缩血细胞并增强血液凝固。在吸收水分后，形状固定的 TRAP-Sp 具有足够的机械强度和高回弹性，可以快速扩张并对伤口施加压力。固定在海绵上的 TRAP 可以通过主动途径激活黏附的血小板。此外，细胞毒性、溶血和组织学评价进一步突出了 TRAP-Sp 的充分生物相容性。由于具有优异的止血性能和生物安全性，这种海绵可能成为一种有前途的用于失控性和非压迫性出血的局部止血剂。
需要创新的止血材料来治疗失控性和非压迫性出血。本手稿描述了一种通过发泡技术、交联反应和化学固定凝血酶受体激动肽（TRAP）合成的快速形状恢复止血海绵，具有主动和被动止血性能。与血液接触时，形状固定的海绵不仅可以快速恢复其原始形状并浓缩血小板和红细胞，还可以有效地激活黏附的血小板。这种双重功能的海绵在大鼠股动脉出血模型中具有优异的止血效果，并且可以控制穿透性肝脏伤口的非压迫性出血。因此，我们相信这种海绵可能成为一种有前途的用于失控性和非压迫性出血的局部止血剂。
