Bio-inspired, bio-degradable adenosine 5′-diphosphate-modified hyaluronic acid coordinated hydrophobic undecanal-modified chitosan for hemostasis and wound healing

Abstract

Uncontrolled hemorrhage and wound infection are crucial causes of trauma-associated death in both the military and the clinic. Therefore, developing an efficient and rapid hemostatic method with biocompatibility, easy degradation, and wound healing is of great importance and desirability. Inspired by spontaneous blood cell plug formation in the hemostasis process, an adenosine 5′-diphosphate modified pro-coagulation hyaluronic acid (HA-ADP) coordinated with enhanced antibacterial activity of undecanal-modified chitosan (UCS) was fabricated through physical electrostatic cross-linking and freeze-drying. The as-prepared hydrogel sponges showed a porous structure suitable for blood cell adhesion. In particular, the hydrogel exhibited excellent antibacterial ability and promoted the adhesion of platelets and red blood cells, thus inducing a prominent pro-coagulation ability via platelet activation, which exhibits a shorter hemostasis time (58.94% of control) in vitro. Compared with commercially available CELOX and gelatin sponge (GS), HA-ADP/UCS accelerates hemostasis and reduces blood loss in both rat tail amputation and rat artery injury models. Furthermore, all the samples exhibited superior cytocompatibility and biodegradability. Due to these performances, HA-ADP/UCS promoted full-thickness skin defect healing significantly in vivo. All the properties of HA-ADP/UCS suggest that it has great potential for translation as a clinical application material for hemostatic and wound healing.

Graphical abstract

Highlights

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  Using adenosine 5'-diphosphate, a physiologically platelet agonist, to modify hyaluronic acids to promote hemostatic effect.

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  Using undecanal to modify Chitosan fabricated with HA-ADP via electrostatic interactions and noncovalent crosslinking method.

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  The hydrogel sponges have excellent antibacterial properties related to the bacterial disruption abilities of UCS.

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  HA-ADP/UCS posed a great hemostatic performance, promoting wound healing by regulating inflammatory response in early stage.