Chitosan-Based Biomaterials for Hemostatic Applications: A Review of Recent Advances

Abstract

Hemorrhage is a detrimental event present in traumatic injury, surgery, and disorders of bleeding that can become life-threatening if not properly managed. Moreover, uncontrolled bleeding can complicate surgical interventions, altering the outcome of surgical procedures. Therefore, to reduce the risk of complications and decrease the risk of morbidity and mortality associated with hemorrhage, it is necessary to use an effective hemostatic agent that ensures the immediate control of bleeding. In recent years, there have been increasingly rapid advances in developing a novel generation of biomaterials with hemostatic properties. Nowadays, a wide array of topical hemostatic agents is available, including chitosan-based biomaterials that have shown outstanding properties such as antibacterial, antifungal, hemostatic, and analgesic activity in addition to their biocompatibility, biodegradability, and wound-healing effects. This review provides an analysis of chitosan-based hemostatic biomaterials and discusses the progress made in their performance, mechanism of action, efficacy, cost, and safety in recent years.

Keywords: blood–material interaction; chitosan-based composites; hemostasis; topical hemostatic agents.

Figure 1

Main complications of uncontrolled bleeding in the intraoperative environment.

Figure 2

Schematic illustration of multiple external hemostatic materials for hemorrhage control.

Figure 3

Intraoperative aspects of different hemostatic materials used in cardiovascular surgery: bone wax—(a) physical aspect of bone wax (blue arrow) and (b) sternum aspect after the application of bone wax (white arrows); (c) cellulose-based material, type Surgicel Original; and (d) cellulose-based material, type Surgicel Fibrillar.

Figure 4

Sources, chemical structures of chitin and chitosan, and chitosan’s main forms.

Figure 5

Hemostatic mechanism of chitosan-based material: the aggregation of erythrocytes occurs due to the interaction between positively charged chitosan and negatively charged molecules present on the surface of erythrocytes.

Figure 6

SEM analysis of (a) chitosan fiber, (b) chitosan sponge, and (c) the in vivo assessment of the hemostatic efficacy of dressings tested on a rat femoral artery hemorrhage model. Figure is licensed under CC-BY 4.0 [124].

Figure 7

Characterization of the chitosan dressing: (a) Fourier-transform infrared spectroscopy results; (b) morphology observations using scanning electron microscopy; (c) cytolysis activity measurement for biocompatibility evaluation (* p < 0.05; 24 and 48 h incubation); (d) relative abundance of most predominant bacteria identified in wound-contact chitosan and regular gauze dressings up to 6 days post-surgery (D1 = day 1, D6 = day 6). Figure is licensed under CC-BY 4.0 [125].

Figure 8

Hemostasis in a liver injury model (I: bleeding; II: hemostasis; III: aspect of the wound after hemostasis): (a) time of hemostasis; (b) mass of blood loss; (c) and Calcein-AM/PI double staining for L929 cells, * p < 0.05 and ** p < 0.01; (d). Figure is licensed under CC-BY 4.0 [128].

Figure 9

Scanning electron microscopy image of ChSp (a) and ChEsM (b), blood sorption (c), and hematological parameters: platelet (e), platelet distribution width (d), and mean platelet volume (f) after interacting with blood. ChSp (g) and ChEsM (h) live/dead staining with FDA/PI after 48 h of cell cultivation. Figure is licensed under CC-BY 4.0 [133].