【摘要】 为解决传统明胶基止血材料存在的吸水膨胀导致组织压迫风险、化学交联剂潜在毒性，以及力学强度和降解速率不可控等问题，采用甲基丙烯酸酐(MA)修饰鱼明胶，赋予甲基丙烯酰化明胶(GelMA)可被光引发交联的特性，规避化学交联剂带来的毒性风险。并采用静电纺丝技术将其加工为纤维膜形式，不仅可缓解组织受压风险，又能利用其高比表面积、多孔性、高孔隙率实现快速浓缩血液、凝集血细胞。体外止血测试证明，相比于市售明胶海绵，该GelMA纤维膜的止血时间与血液凝固指数分别缩短至明胶海绵的66.49%和30.69%。通过调控MA的添加量，制备了不同甲基丙烯酰基取代度的GelMA纤维膜，通过微观形貌观察、拉伸性能测试、体外酶解实验等系统性探究了取代度对GelMA纤维膜的影响，成功证明基于取代度(18%～69%)的调控，可得到具备不同降解周期(2～60 h)与拉伸强度(0.13～3.25 MPa)的GelMA纤维膜。这种可定制的力学与降解特性使其能够适配急性出血控制(高取代度、慢降解)与微创手术止血(低取代度、快吸收)等不同临床场景，为开发高效安全的可吸收止血材料提供了创新解决方案。更多还原

【Abstract】 Objective The purpose of this study is to develop a new absorbable hemostatic dressing based on methacryloyl gelatin(GelMA) electrospun fiber membrane, so as to solve the clinical limitations associated with the conventional gelatin-based hemostatic materials(such as sponge and hydrogel). Such limitations include the risk of tissue compression caused by water absorption and swelling, the potential toxicity of chemical crosslinking agent, and the uncontrollable mechanical strength and degradation rate. At the same time, the influence of the degree of substitution on the properties of GelMA fiber membrane was systematically investigated, and the flexible regulation of the mechanical strength, degradation rate and hemostasis effect of the material was realized, thus adapting to the clinical needs of different hemostasis scenarios(such as arterial bleeding and venous oozing). Method GelMA with different degrees of substitution(18%-69%) was prepared by modifying fish gelatin with methacrylic anhydride(MA), and processing into fiber membrane by electrostatic spinning technology. The comprehensive properties of the fiber membrane were evaluated by microscopic observation, tensile test, enzymatic hydrolysis experiment in vitro and coagulation index in vitro. At the same time, compared with commerical gelatin sponge and gauze, its hemostatic advantage was verified. Results Firstly, the degree of substitution of GelMA functional groups was successfully regulated by MA. With the increase of MA content, the degree of substitution gradually increased, and the increase slowed down when MA concentration was greater than 3%. With the increase of the degree of substitution, the crosslinking degree of GelMA fiber membrane increased, so the morphology became increasingly stable and the fibers were interconnected, leading to the gradual increase in the tensile strength and elastic modulus and gradual decrease in elongation at break. Secondly, growing the degree of substitution caused the degradation rate to slow down. In the same enzyme solution environment, the mass of GelMA(degree of substitution is 18%) is only about 6.33% after 2 h, while that of GelMA(degree of substitution is 69%) is still about 31% after 60 h, confirming the regulation of the degree of substitution on the degradation rate of GelMA. In terms of hemostasis, the degree of substitution showed no significant effect on hemostasis, so the hemostatic effect of GelMA fiber membrane with different degrees of substitution remained similar, but better than that of commercial gelatin sponge. In addition, GelMA(degree of substitution is 38%) hydrogel and GelMA(degree of substitution is 38%) sponge were prepared and compared. The results of blood coagulation index showed that the coagulation effect of hydrogel and sponge was not as good as that of GelMA fiber membrane, which proved the superiority of fiber membrane.Conclusion GelMA fiber membrane hemostatic dressing with adjustable performance was successfully developed and the conventional chemical crosslinking agent was replaced by photocrosslinking system to avoid toxicity risk. The shape of fiber membrane was found to significantly reduce the expansion rate(compared with sponge) eliminating the risk of tissue compression. Control over the degree of substitution to facilitated precise adjustment of degradation time period(2-60 h) and tensile strength(0.13-3.25 MPa), which are applicable to different hemostasis scenarios. In vitro experiments show that the coagulation time of fiber membrane is shortened to 66.49% of that of sponge, and blood congulation index is reduced to 30.69% of that of sponge, and its anti-swelling property is better than hydrogel and sponge. In the future, it is necessary to verify the in vivo performance through animal experiments and optimize the materials to cope with the bleeding scene with strong adhesion or incompressible.更多还原