Development of carboxymethyl cellulose nonwoven sheet as a novel hemostatic agent

doi:10.1016/j.jbiosc.2014.10.026

Journal of Bioscience and Bioengineering

Volume 119, Issue 6, June 2015, Pages 718-723

https://doi.org/10.1016/j.jbiosc.2014.10.026 Get rights and content

Carboxymethyl cellulose (CMC) is a plant-derived material that has high biocompatibility and water solubility. We developed a CMC nonwoven sheet as a hemostatic agent by carboxymethylating a continuous filament cellulose nonwoven sheet. The CMC nonwoven sheet was able to absorb water and dissolve in it. The rates of absorption and dissolution depended on the degree of carboxymethylation. After dissolving in blood, CMC accelerated clot development (possibly owing to the incorporation of CMC into fibrin fibers) and increased the viscosity of the blood, both of which would contribute to the improved blood clotting of an injured surface. In vivo experiments using a rat tail cutting method showed that a CMC nonwoven sheet shortened the bleeding time of the tail when applied to the cut surface. The hemostatic effect of the CMC nonwoven sheet was almost at the same level as a commercial hemostatic bandage. These results suggest that a CMC nonwoven sheet could be used as a novel sheet-type hemostatic agent.

Section snippets

Materials and methods

Sodium hydroxide, acetic acid, and sodium chloroacetate were purchased from Kishida Chemical (Osaka, Japan). Ethanol, calcium chloride (CaCl₂), and sodium citrate were purchased from Wako Pure Chemical Industries (Osaka, Japan). Normal saline was purchased from Otsuka Pharmaceutical (Tokyo, Japan). Standard human plasma (Coagtrol N) was purchased from Sysmex (Hyogo, Japan) and human fresh frozen plasma (FFP) was supplied by the Japanese Red Cross Society (Tokyo, Japan).

Properties of the fabricated CMC nonwoven sheet

A CMC nonwoven sheet was fabricated by carboxymethylating the continuous filament cellulose nonwoven sheet that we had developed previously (22). The morphology of the nonwoven sheet did not change after carboxymethylation (Fig. 1A). Thickness and fiber diameter of the nonwoven sheet also did not change so much after carboxymethylation; from 0.44 mm to 0.48 mm in thickness and 11.0–11.1 μm in fiber diameter. On the other hand, density of the nonwoven sheet was increased from 0.19 to 0.31 g/m³

Discussion

Nonwoven sheets of CMC were fabricated by carboxymethylation of continuous filament cellulose nonwoven sheets in this study. ATR-IR measurement and titration analysis revealed that we were able to control the DS of the CMC nonwoven sheets by changing the carboxymethylation reaction time. This difference in DS significantly affected the water absorption and dissolution property of CMC nonwoven sheets. While an increase in DS value decreased the rate of water absorption of CMC nonwoven sheets,

Acknowledgments

We thank M. Aoshima for the useful discussion. We also acknowledge Q. Pan for her help in conducting ATR-IR measurements. S. Ohta is grateful to the Research Fellowship (PD, no. 5621) from the Japan Society for the Promotion of Science (JSPS).

References (31)

M. Burkatovskaya et al.
Use of chitosan bandage to prevent fatal infections developing from highly contaminated wounds in mice
Biomaterials
(2006)
H. Hori et al.
Analysis of the major epitope of the α2 chain of bovine Type I collagen in children with bovine gelatin allergy
J. Allergy Clin. Immunol.
(2002)
J.E. Bjorenson et al.
Effects of hemostatic agents on the pH of body
J. Endod.
(1986)
J.L. Ibarrola et al.
Osseous reactions to three hemostatic agents
J. Endod.
(1985)
O. Akturk et al.
Evaluation of sericin/collagen membranes as prospective wound dressing biomaterial
J. Biosci. Bioeng.
(2011)
S.C. Roy et al.
The effect of TiO2 nanotubes in the enhancement of blood clotting for the control of hemorrhage
Biomaterials
(2007)
Y. Ogushi et al.
Synthesis of enzymatically-gellable carboxymethylcellulose for biomedical applications
J. Biosci. Bioeng.
(2007)
D.A. Hett et al.
Sonoclot analysis
Br. J. Anesth.
(1995)
H. Kihara et al.
Antithrombotic activity of AT-1015, a Potent 5-HT_2A receptor antagonist, in rat arterial thrombosis model and its effect on bleeding time
Eur. J. Pharmacol.
(2001)
A.J. Varma et al.
Calcium complexation by low molecular weight dicarboxycellulose in aqueous solution
Carbohydr. Polym.
(2001)

M.B. Dowling et al.

A self-assembling hydrophobically modified chitosan capable of reversible hemostatic action

Biomaterials

(2011)

H.E. Achneck et al.

A comprehensive review of topical hemostatic agents

Ann. Surg.

(2010)

W.M. Abbott et al.

The effectiveness and mechanism of collagen induced topical hemostasis

Surgery

(1975)

R.K. Low et al.

Microfibrillar collagen hemostat during laparoscopically directed liver biopsy

J. Laparoendosc. Surg.

(1993)

V.K. Frantz et al.

Hemostasis with absorbable gauze (Oxidized Cellulose)

Ann. Surg.

(1944)

Cited by (49)

Large-scale manufacturing of soluble hemostatic spacer dressing with excellent mechanical and comfortable properties
2023, Materials and Design
Death from acute hemorrhage is a major life-threatening. Spacer fabrics-based composite dressings have been widely concerned because of their good hemostasis and protection in wound healing, but the poor liquid absorption and compression recovery properties hinder their utilization. Herein, we report a soluble hemostatic spacer dressing based on a braided yarn of PTFE (core yarn)/carboxymethylated viscose (shell yarn) as the skin contact layer, a wrapped yarn of nylon monofilament (core yarn)/Coolmax (shell yarn) as the spacer layer, and UHMWPE yarn as the waterproof layer for wound healing. Among these, carboxymethylated viscose can stop bleeding, while PTFE has low adhesion and ensures the structural integrity of the spacer fabric. Moreover, the nylon monofilament can endow the dressing with excellent comfortability, resilience, and fatigue resistance. Coolmax can absorb blood. The as-prepared spacer dressing shows excellent mechanical, comfortable, and hemostasis properties. F2 had a hemostasis time of 5.15 min, a low coagulation index of 7.96%, a hemolysis rate of 0.98%, and a blood absorption rate of 159.09%. This work presents an integrated molding method to achieve large-scale manufacturing of spacer dressing, which is expected to guide materials design for future innovations in biomedical applications.
Strongly-adhesive easily-detachable carboxymethyl cellulose aerogel for noncompressible hemorrhage control
2023, Carbohydrate Polymers
Hemostats that can strongly adhere to wound tissue and are easy to remove when stopping bleeding are favored for the control of noncompressible hemorrhage. Here, we prepared a citric acid (CA)-crosslinked and N-hydroxysuccinimide (NHS) ester-activated carboxymethyl cellulose (CMC-NHS) aerogel for noncompressible hemostasis. CA was used to crosslink CMC to form a strengthened structure. NHS ester was introduced to activate the adhesion of CMC-NHS aerogel to wound tissue and promoted blood coagulation through the formation of amide crosslinks between CMC and erythrocytes and free blood proteins. The plentiful carboxyl groups could also trigger the intrinsic coagulation pathway. Thus, the aerogel could quickly adhere to wound tissue to stop bleeding, and then could be easily removed when fully hydrated as CMC was dissolved at the adhesion interface. The aerogel also had good biocompatibility and antibacterial capability. Overall, CMC-NHS aerogel is a competitive hemostat for the control of noncompressible hemorrhage.
Rapid promoting thrombus formation and fibrin cross-linked Bi-doped mesoporous bioglass for hemostatic agent
2022, Materials Today Chemistry
Despite decades of development of biomaterials, hemorrhage remains a primary cause of death in surgeries and accidents. Effective hemostatic agents that induce hemostasis and rapid coagulation are needed by surgeons and in daily life. Here, we report on the application of hemostatic agents by studying mesoporous bioglass (MBG) doped with bismuth oxide via a two-step acid-catalyzed self-assembly (TSACSA) process. The results show that all the samples have an ordered mesoporous structure and a large surface area, especially MBG doped with 2 mol% Bi₂O₃ has the highest specific surface area (704.06 m²/g). MBG doped with different proportions of Bi accelerated the intrinsic coagulation pathway and was not found to exhibit severe erythrocyte cytotoxicity. It is worth noting that MBG added with 1 and 2 mol% Bi₂O₃ had higher thrombus formation, fibrin polymerization rates, and platelet adhesion; however, higher content of Bi₂O₃ (3 mol%) may affect the consequence of coagulation. These results of our investigation suggest that MBG doped with a low range of Bi is a potential hemostatic biomaterial for clinical applications.
Silver-loaded carboxymethyl cellulose nonwoven sheet with controlled counterions for infected wound healing
2022, Carbohydrate Polymers
Citation Excerpt :
A feature of CMC is that its property, such as hydrophilicity and dissolution rate, can be easily altered by the degree of substitution (DS) of carboxymethyl groups or their counterions. Previously, we developed CMC nonwoven sheets with tunable DS and counterions, enabling controllable water absorption and dissolution (Ohta et al., 2015; Qi et al., 2018). By optimizing these properties, their potential use as topical hemostatic agents and bone regeneration scaffolds has been demonstrated (Ohta et al., 2015; Qi et al., 2018; Sakamoto et al., 2019).
Carboxymethyl cellulose (CMC) is a promising material for moist wound healing, and silver loading onto CMC has been examined for anti-bacterial activity. In this study, we developed silver-loaded CMC nonwoven sheets with different counterions, namely sodium CMC (CMC-Na/Ag) and partially protonated CMC (CMC-H/Ag), to examine their anti-bacterial and wound-healing properties. Owing to the presence of counter protons, CMC-H/Ag showed slower water adsorption, dissolution, and Ag release than CMC-Na/Ag. In addition, CMC-H/Ag and CMC-Na/Ag exhibited differences in anti-bacterial activities in shake-flask and inhibition zone tests in vitro. An in vivo experiment using a pressure ulcer mouse model with Pseudomonas aeruginosa infection showed that CMC-Na/Ag significantly accelerated wound healing compared to CMC-H/Ag and a commercially available Ag-loaded CMC nonwoven sheet, Aquacel Ag. These results suggest the importance of controlling CMC counterions and the therapeutic potential of the developed product as a wound dressing.
Rapid hemostasis and excellent antibacterial cerium-containing mesoporous bioactive glass/chitosan composite sponge for hemostatic material
2022, Materials Today Chemistry
Citation Excerpt :
Collagen has unsatisfactory mechanical properties and a fast dissolution rate. Oxidized cellulose hemostatic materials are acidic, possibly causing inflammation and hindering tissue repair [11]. GSs are not conducive to emergency treatment, owing to their poor adhesion properties.
Rapid and effective hemostasis is key to controlling bleeding and reducing mortality. Here, a composite hemostatic sponge (Ce-MBG/CHT) of cerium-containing mesoporous bioactive glass (Ce-MBG) and chitosan (CHT) was prepared by a freeze-drying technique and compared with the commercially available gelatin sponge (GS), to further evaluate the hemostatic performance of composite sponge materials. The results indicate that the pore structure, porosity, and water absorption of the sponge improved following the addition of Ce-MBG. Whole blood coagulation studies suggested that Ce-MBG/CHT has superior hemostatic properties to GS and validated in vitro thrombosis, platelet adhesion and blood compatibility. In vitro coagulation studies showed that factor XII was activated by the addition of Ce-MBG, inducing the intrinsic coagulation pathway. Furthermore, we evaluated the cytocompatibility of samples after contact with L929 cells for 24, 48, and 72 h via the cytotoxicity test. Compared with GS, 4Ce-MBG/CHT was more efficient against E. coli and S. aureus. All these results indicate that Ce-MBG/CHT sponges are likely useful for rapid hemostasis.
Flexible biomimetic hollow Al<inf>2</inf>O<inf>3</inf> fibers for safe and effective hemostasis
2022, Materials and Design
Citation Excerpt :
When pressed on bleeding wounds, the high-water intake capacity of CFs enables them to soak up blood rapidly to concentrate red blood cells (RBCs), platelets, and clotting factors at the bleeding site, and exhibit procoagulant activities [19]. Though there are now several studies focusing on improving the hemostatic potential of CFs, such as chemical group modification (e.g., carboxymethylation) [20,21] and combination with hemostatic materials (e.g., chitosan) [22,23], the hemostatic effect of CFs does not meet the need of using in harsh environment, especially in the condition of fibrin dysfunction. Alumina (Al2O3) is attracting much more attention in the field of biomedical materials [24,25].
Uncontrolled hemorrhage due to trauma and post-traumatic fibrin dysfunction is a significant cause of death worldwide, and an effective hemostatic material is needed to achieve safe and portable hemostasis in situation of both healthy blood coagulation and fibrin dysfunction. Besides, it is desirable to develop a hemostat material that is active despite long-term storage at harsh temperatures to meet the need of using in harsh condition. Here, biomimetic “cotton-like” hollow Al₂O₃ fibers (HFs) are fabricated, whose clotting strategy is incompletely dependent on the physiological coagulation mechanisms, to address the above challenges. The HFs, with hollow porous 3-dimensional (3D) structure, large specific surface area and negatively Zeta potential, can not only concentrate blood components, activate intrinsic coagulation pathway, and promote the activation of platelets and fibrin but entrap anticoagulated blood components in a network of HFs to form HFs-based clots with similar morphological characteristics to fibrin-based clots even after exposure to harsh environments. The application of HFs can accelerate hemostasis as compared to gauze, cotton, and hemostatic sponge. The outstanding hemostatic efficacy, in combination with biocompatibility, thermal robustness, portable application and simple fabrication make HFs a promising hemostatic agent for effective and cheap hemorrhage control.

View all citing articles on Scopus

View full text

Development of carboxymethyl cellulose nonwoven sheet as a novel hemostatic agent

Section snippets

Materials and methods

Properties of the fabricated CMC nonwoven sheet

Discussion

Acknowledgments

Biomaterials

J. Allergy Clin. Immunol.

J. Endod.

J. Endod.

J. Biosci. Bioeng.

Biomaterials

J. Biosci. Bioeng.

Br. J. Anesth.

Eur. J. Pharmacol.

Carbohydr. Polym.

Biomaterials

A comprehensive review of topical hemostatic agents

Ann. Surg.

The effectiveness and mechanism of collagen induced topical hemostasis

Surgery

Microfibrillar collagen hemostat during laparoscopically directed liver biopsy

J. Laparoendosc. Surg.

Hemostasis with absorbable gauze (Oxidized Cellulose)

Ann. Surg.