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.

Key words: methacryloyl gelatin, electrospinning, absorbable hemostatic material, degree of substitution, controllable degradation, hemostatic dressing, fiber membrane