Manipulated Molecular Design Engineering for Multi-Functional Flexible  Hemostatic Bio-Hydrogel

Abstract

Releasing the biomedical application potential of chitosan has become an emerging research hotspot for effective hemostatic agents. However, designing a flexible chitosan-based hemostatic agent with self-adhesion feature in humid environments and rapid hemostasis performance is still a persistent challenge. Herein, a self-adhesive hydrogel (DCS-PEGSH gel) with a typical multi-level pore structure cross-linked by 3-(3,4-Dihydroxyphenyl) propionic acid modified chitosan (DCS) and sebacic acid-terminated polyethylene glycol-modified by p-hydroxybenzaldehyde (PEGSH) was successfully synthesized. The bio-hydrogel displays favorable cytocompatibility, suitable stretchability (~780%), and water absorbability (1300% ± 50%), which can be precisely regulated by the proportion of PEGSH polymer in the gel network. The strong adhesion (68.5 kPa) allows long-term stability of the assembled hydrogel on pigskin in both static and dynamic humid environments, as well as firm adherence to the bleeding wound without shedding. The Rat hemorrhage model was established to certificate that the hydrogel has lower blood clotting time (50 s) and blood clotting index (BCI, 41) compared to a commercial chitosan sponge (288 s, BCI 65). Notably, the amount of blood loss from liver in rats is reduced almost 90% compared with the control group. This study provides a novel prospect including both molecular design and structural regulation for developing chitosan-based hydrogel with self-adhesive, self-healing, stretchability, biocompatibility, antibacterial ability, and antioxidant properties for further biomedical application regarding emergency hemostasis, particularly in joints and extremities.