Chitosan-based multifunctional flexible hemostatic bio-hydrogel.

Abstract

Realizing the potential application of chitosan as an effective biomedical hemostatic agent has become an emerging research hotspot. However, fabricating a flexible chitosan-based hemostatic bio-hydrogel with self-adhesion feature in humid conditions and rapid hemostasis capability remains a challenge. Herein, we reported the development of chitosan-based hydrogels (DCS-PEGSH gels) with typical multilevel pore structures, which were cross-linked by 3-(3,4-dihydroxyphenyl) propionic acid-modified chitosan (DCS) and sebacic acid-terminated polyethylene glycol modified by p-hydroxybenzaldehyde (PEGSH). By precisely regulating the proportion of PEGSH, the fabricated bio-hydrogels displayed favorable cytocompatibility, suitable stretchability (∼780%), and blood absorbability (1300% ± 50%). Moreover, the strong adhesion (∼68.5 kPa) of the assembled bio-hydrogel ensured its firm adherence on pigskin and on bleeding wound in both static and dynamic humid environments without shedding, thus providing a long service life. The fabricated hydrogels exhibited shorter blood clotting time (50 s) and lower blood clotting index (BCI, 41) than the commercial chitosan sponge (288 s, BCI 65). Notably, the amount of blood loss from the liver in mice was reduced by almost 90% as compared to that for the control group. This study paves a solid way for developing a chitosan-based hydrogel with self-adhesive, self-healing, stretchability, biocompatibility, and antibacterial and antioxidant properties through molecular design and structural regulation, which will enable the biomedical application of chitosan in emergency hemostasis, particularly in joints and extremities. STATEMENT OF SIGNIFICANCE: The design and preparation of multifunctional integrated green adhesive bio-hydrogels while avoiding the use of organic solvents and toxic chemical reagents has been an emerging challenge. Herein, a flexible chitosan-based hemostatic bio-hydrogel that integrates multifunctional properties was successfully synthesized. The bio-hydrogel displayed suitable stretchability (780%) and blood absorbability (1300% ± 50%). Moreover, the strong adhesion (68.5 kPa) ensured firm adherence of the assembled hydrogel on pigskin and on the bleeding wound site in both static and dynamic humid environments without shedding, thus providing a long service life. In addition, the designed hydrogel showed good compatibility and antibacterial performance. The dynamic Schiff base endowed the bio-hydrogel with excellent self-healing performance without any external stimuli.