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. 2021 Dec 9;13(12):2127. doi: 10.3390/pharmaceutics13122127

Table 1.

Hemostatic functions of natural polymeric systems.

Name [Ref.] Polymeric System Mechanism of Action Case Study Model Findings
Chitosan [50,51,81,95,96] Chitosan/ε-polylysine hydrogel
Chitosan-nano-bioglass composite
CMCS-TA-BDBA hydrogel PVA/CSENDHM nanofibrous membrane.
Employed for hemostasis, in the form of powder, films, sponges, hydrogels, particles, fibers.
Powders: Manual compression, as well as the interaction with erythrocytes, provide rapid coagulation.
Hydrogels: Facilitates barrier formation and prevents blood flow from the cavity.
In vivo study of
acute liver puncher models in rats, rabbits, and pigs.
Anti-microbial and anti-bacterial activities; excellent adhesion ability; rapid blood coagulation; high water absorption; biocompatible.
Collagen [97] CollaStat®® (Collagen and thrombin) and Floseal®® (Gelatin and thrombin) Provides a site for platelet adherence, activation, and aggregation. The activated platelets agglomerate around the wound and stop the blood flow. The hemostatic efficacy of CollaStat®® and FloSeal®® have been compared in a rabbit jejunal artery injury model. The mean hemostasis time for CollaStat®® was found to be significantly shorter compared to Floseal®® (64.0 ± 0.5 s vs. 84.0 ± 7.8 s).
Dextran Aldehyde dextran sponge Accelerates coagulation by rapid wound closure, cells’ initiation, and aggregation, as well as coagulation factors’ aggregation on the wound site. In vivo study of the femoral artery and liver injuries model in rabbits. Low cytotoxicity; remarkable blood loss; quick blood absorption and strong tissue adhesion.
Gelatin [56,57,58,98] FloSeal®® (Gelatin-thrombin granules). Graphene oxide-gelatin aerogels.
Curcumin-alginate-gelatin sponge. m-TG-thrombin-gelatin
Gelatin granules swell when they come in contact with the blood. These swollen granules stop hemorrhage by blocking the bleeding site. In vivo (liver and spleen rupture model in swine, rat liver trauma model, liver abrasion model in rabbit).
In vitro (platelets adhesion, whole blood-clotting time, total blood absorption).
Excellent clot integration into the surrounding tissues; safe to implant in the body; reduced blood-clotting time; potential for preventing tumor recurrence.
Alginate [65,67,99,100] PGA/alginate/AgNP
Alginate fibers
Alginate-PHMB-AgNP polyamide nanocomposites
Hydroxy apatite/alginate granules.
Calcium ions are released in exchange for sodium ions when calcium alginate comes in contact with blood.
These released calcium ions promote prothrombin activation in the clotting cascade which leads to rapid hemostasis. Alginate granules swell enough to block the bleeding site.
The alginate-based hemostatic dressing efficacy was characterized by blood-clotting time. Biocompatibility of the dressings was studied using degradation weight change. pH-sensitive swelling properties; excellent hemostatic performance; anti-bacterial properties.
Cellulose [49,70,74,101] Cellulose-modified chitosan foam sponge. Oxidized cellulose patch (Surgicel®®). Facilitates hemostasis by quickly absorbing liquid, entrapping platelets and erythrocytes, and increasing blood coagulating factors. Rabbit femoral artery injury model. Mouse tail amputation model. Excellent water-absorbing ability, improved mechanical strength; low hemolysis rate, benign cytotoxicity; good resilience ability; superior hemostasis; good candidate for chronic wound treatment.
Hyaluronic acid [32,59,82,94,102] GelMA-HA-NB hydrogel
HA/gelatin hydrogel
HAPPI
HA-Serotonin hydrogel
HA-based hydrogels act as tissue sealants for hemorrhage control. In vivo (rat femoral artery bleeding model, liver bleeding rat model, mouse tail bleeding model, mouse abdominal wall abrasion model).In vitro (shear test, adhesion test, compression test, total blood-clotting time test) Shorter gelation time (< 2 min), good stability; strong burst strength; excellent sealant strength; improved hemostatic capability; potential application as a trauma wound sealant.
Starch [90,93,94,103,104] kCA-coated starch/cellulose nanofibers
St-Dopa hydrogel
SPS-STMP hydrogel
TRAP-Starch-PEG sponge
When Ca2+ CPSMs are applied to the bleeding sites, it provides sites for RBCs and platelets’ adhesion, and forms gel-like matrices which block the irregular bleeding. Starch-based sponge provides pressure to the wound and promotes hemostasis. In vivo mouse tail amputation method; rat tail bleeding model; rat liver laceration model. Hydrogels: rapid sol-gel transition; good swelling ratio; excellent cyto/hemocompatibility.
Sponge: high resilience; good mechanical strength; high expandable; useful as a topical hemostatic agent for uncontrolled and non-compressible hemorrhage.

m-TG—microbial transglutaminase; GelMA—methacrylate gelatin; NB—butanamide; κCA—kappa carrageenan; St—Starch; SPS—porous starch; STMP—Sodium trimethaphosphate; AgNP—Silver nanoparticles; PHMB—Poly(hexamethylene) biguanide; CMCS–O-carboxymethyl chitosan; TA—Tannic acid; BDBA—1,4-benzenediborinic acid; PVA—Polyvinyl alcohol; CSENDMH—quaternary ammonium N-halamine chitosan.