Department of Orthopaedics, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
College of Physical Science and Technology, Sichuan University, Chengdu 610064, China.
Mater Sci Eng C Mater Biol Appl. 2020 Apr;109:110556. doi: 10.1016/j.msec.2019.110556. Epub 2019 Dec 13.
Absorbable polyelectrolyte complexes-based hemostats are promising for controlling hemorrhage in iatrogenic injuries during surgery, whereas their hemostatic efficacy and other performances require further improvement for clinical application. Herein, spherical mesoporous bioglass nanoparticles (mBGN) were fabricated, and mBGN-polyelectrolyte complexes (composed of carboxymethyl starch and chitosan oligosaccharide) nanocomposites (BGN/PEC) with different mBGN contents were prepared via in situ coprecipitation followed by lyophilization. The effect of various mBGN content (10 and 20 wt%) on morphology, zeta potential, water absorption, degradation behavior and ion release were systematically evaluated. The in vitro degradability was dramatically promoted and a more neutral environment was achieved with the incorporation of mBGN, which is preferable for surgical applications. The in vitro coagulation test with whole blood demonstrated that the incorporation of mBGN facilitated blood clotting process. The plasma coagulation evaluation indicated that BGN/PEC had increased capability to accelerate coagulation cascade via the intrinsic pathway than that of the PEC, while have inapparent influence on the extrinsic and common pathway. The in vivo hemostatic evaluation in a rabbit hepatic hemorrhage model revealed that BGN/PEC with 10 wt% mBGN (10BGN/PEC) treatment group had the lowest blood loss, although its hemostatic time is close to that of 20BGN/PEC treatment group. The cytocompatibility evaluation with MC3T3-L1 fibroblasts indicated that 10BGN/PEC induced a ~25% increase of cell viability compared to the PEC at days 4 and 7, indicating improved biocompatibility. These findings support the promising application of absorbable BGN/PEC with optimized mBGN content as internal hemostats and present a platform for further development of PEC-based hemostats.
基于可吸收聚电解质复合物的止血剂在控制手术中医源性损伤引起的出血方面具有很大的应用前景,然而其止血效果和其他性能需要进一步改进才能应用于临床。在此,我们制备了球形介孔生物玻璃纳米颗粒(mBGN),并通过原位共沉淀后冻干法制备了不同 mBGN 含量的 mBGN-聚电解质复合物(由羧甲基淀粉和壳寡糖组成)纳米复合材料(BGN/PEC)。系统评价了不同 mBGN 含量(10 和 20wt%)对形态、Zeta 电位、吸水率、降解行为和离子释放的影响。随着 mBGN 的加入,体外降解性能显著提高,环境更趋中性,更有利于手术应用。全血体外凝血试验表明,mBGN 的加入促进了血液凝固过程。血浆凝血评估表明,BGN/PEC 比 PEC 更能通过内在途径加速凝血级联反应,而对外在途径和共同途径没有明显影响。兔肝出血模型的体内止血评价表明,mBGN 含量为 10wt%的 BGN/PEC(10BGN/PEC)治疗组的出血量最低,尽管其止血时间与 20BGN/PEC 治疗组相近。用 MC3T3-L1 成纤维细胞进行的细胞相容性评价表明,与 PEC 相比,10BGN/PEC 在第 4 天和第 7 天可使细胞活力提高约 25%,表明其具有更好的生物相容性。这些发现支持了具有优化 mBGN 含量的可吸收 BGN/PEC 作为内部止血剂的应用前景,并为基于 PEC 的止血剂的进一步开发提供了一个平台。