2019 SCIENCELINE  
Journal of Life Science and Biomedicine  
J Life Sci Biomed, 9 (1): 34-41, 2019  
ISSN 2251-9939  
Comparative efficacy of the hemostatic implant made of the  
cellulose derivatives on the model of parenchymatous  
hemorrhage from liver  
Bahodir Abdimusaevich Ismailov, Rustam Abrarovich Sadykov, and Bahodir Mirsagatovich Mirzaahmedov  
Republican Specialized Surgery Centre named after Academician V.Vakhidov, Tashkent city, Uzbekistan.  
Corresponding author’s Email: bahodirismailov@gmail.com  
ABSTRACT  
Original Article  
PII: S225199391900006-9  
Aim. The aim was to study the comparative efficiency of the hemostatic implant made of the  
cellulose derivatives on a model of the parenchymatous hemorrhage from a liver.  
Methods. Experimental studies on the biocompatibility’s evaluation were conducted in  
Rec.  
Rev.  
Pub.  
15 Nov  
20 Jan  
25 Jan  
2018  
2019  
2019  
accordance with the Russian national standard ISO 10993-6-2011. Operations have been  
performed under the general anaesthetizing with the modeling the parenchymatous  
hemorrhage from the wound of liver. A total of 72 white mature outbred rats of both sexes  
weighing 196.5±2.8 g were used from which 36 ones made up group of comparison using the  
application hemostatic material, Sergicel® FibrillarTM. In the basic group of rodents (36)  
powder Heprocel in equal amounts by weight of 30 mg was applied on a wound.  
Results. From the results it is possible to come to a conclusion that the hemostatic Heprocel  
implant causes on the first day morphological reaction of liver as an inflammation and a  
spread of the connecting tissue, but these processes calm down quickly. An inflammatory  
reaction was less expressed than the control group. To the 30th day in the basic group after  
application of Heprocel biodecomposition of hemostatic implant was being marked, there  
were regenerator processes in the liver’s parenchima especially in the zone of lesion that  
testifies to renewal of liver’s tissue, while in a comparison group an active degradation of  
the application hemostatic material began on the 30th day and an expressed adhesion  
process in an abdominal cavity took place.  
Keywords  
Hemostasis,  
Parenchymatous  
Hemorrhage,  
Liver,  
Cellulose’s derivatives,  
Experimental surgery,  
Hemostatic implant,  
Morphology of liver.  
Conclusion. Hemostatic powder closely adjoins the liver’s tissue, stops bleeding, cases of  
relapse of bleeding were not marked. Histological researches conducted in the dynamics of  
the healing showed that the wounds of liver educed that Heprocel did not cause the  
expressed inflammatory reaction, the zone of lesion did not exceed 150 µm, and the  
biodecomposition started after 14 days.  
INTRODUCTION  
Nowadays a lot of preparations and their combinations possessing the hemostatic activity at local application  
are well-known. All of them, however, have certain limitations. It is possible to attribute materials based on  
gelatin, cellulose and collagen (Spongostan, USA) and combined hemostatic materials (Tachocomb, Austria) to  
traditional hemostatic means. For example, preparations based on collagen possess a low hemostatic activity in  
humid media, badly stop hemorrhage at systemic coagulopathies and thromboblasthemia, have a potential  
possibility of the infection, and are inactivated at autoclaving that substantially reduces their efficiency and  
limits a sphere of application [1].  
Modern hemostatic material Tachocomb presents itself as a sponge of collagen of the horse tendons,  
human lyophilized fibrinogen, pig fibrin, and animal’s aprotinin. Its basic defect is a presence of components of  
animal origin which can cause an allergic reaction [2]. Application of preparations on the basis of gelatin is  
connected with a high probability of the infecting in a zone of the applying the implant [3].  
Implants on the basis of polymeric materials find an increasingly wider use in surgery [4]. Hemostatic  
preparations obtained from the polysaccharides’ derivatives and, first of all, from oxidized cellulose (OC) are of a  
considerable interest [3, 5, 6]. OC accepted internationally after it firstly used in 1945 [7], because of its  
bactericidal properties, favorable biocompatibility, and overall ease of use [8]. Oxidized cellulose possesses a  
hemostatic action and is widely used in surgery for treatment of skin wounds, protractedly non-healing chronic  
ulcers, resection of kidney [9-11]. The principle of the regenerated OC’s hemostatic action is in the change of pH  
media in anoxidosis side (pH 2.5-3.0) that creates favorable conditions for the forming the thrombocyte clot.  
To cite this paper: Ismailov BA, Sadykov RA, and Mirzaahmedov BM. 2019. Comparative efficacy of the hemostatic implant made of the cellulose derivatives on  
the model of parenchymatous hemorrhage from liver. J. Life Sci. Biomed. 9(1): 34-41-; www.jlsb.science-line.com  
Also anoxidosis environment in the zone of lesion contributes to the nonspecific anti-microbe activity of OC [5].  
OC possesses a good biocompatibility and biodegradation, is not toxic, chemically inert, non-soluble in the  
water, has a fibred structure and high mechanical durability [12].  
A hemostatic implant on the plants basis Ankaferd Blood Stopper (ABS, Turkey) was examined for the  
hemostasis from the bone tissue. An inflammatory reaction was evaluated on the amount of inflammation cells:  
0-25% - weak, 25-50% - moderate, 75-100% - expressed. The factors of necrosis were considered on a qualitative  
sign: presence or absence. Besides the inflammatory reaction a number of newly formed osteoblasts were  
estimated. On the scale of Moretton for the implants of bone tissue Ankaferd was determined as an agent which  
does not cause an active inflammation and but assisting the tissue healing [9]. The tissue reaction caused by a  
hemostatic implant is one of the reliable factors of the estimating the biocompatibility of a product and  
conditioned by terms and character of biodegradation [13, 14]. Therefore, the aim of this study was to  
investigate the comparative efficiency of the hemostatic implant made of the cellulose derivatives on a model of  
the parenchymatous hemorrhage from a liver.  
MATERIAL AND METHODS  
Hemostatic Heprocel implant was worked out in SI "Republican Specialized Scientific and Practical  
Medical Center of Surgery named after Academician V.Vakhidov". Basic components of implants were as follow:  
sodium salt of carboxymethyl cellulose, oxidized cellulose and nanocellulose (Patent No. IAP 20160273) [1].  
Experimental studies on the biocompatibility’s evaluation were conducted in accordance with the Russian  
national standard ISO 10993-6-2011. Operations were performed under the general anaesthetizing with the  
modeling the parenchymatous hemorrhage from the wound of liver. 72 white mature outbred rats of both sexes  
weighing 196.5±2.8 g were used from which 36 ones made up a group of comparison with the using the  
application hemostatic material of Sergicel® FibrillarTM. In the basic group of rodents (n=36) powder Heprocel  
in equal amounts by weight of 30 mg was applied on a wound.  
Under inhalation anesthesia (Halothanum) a supramedian laparotomy was performed. On the surface of  
liver a flat wound was formed with a diameter up to one cm, and a depth up to 0.1 cm. From the liver’s wound an  
active parenchymatous bleeding was marked. In the comparative group hemostasis was conducted by the  
applying the hemostatic means Sergicel® FibrillarTM till the stopping the bleeding completely. In the experience  
group a hemostatic powder Heprocel was applied on the bleeding surface. An observance over the possible  
bleeding resumption was conducted during 10 minutes. In the fixed terms animals were taken out of an  
experiment for the estimating the macroscopic changes, and also for the intake of material for histological  
researches. Laboratorial animals were withdrawn from an experiment on the 1 -, 7 -, 14 -, 21 - and the 30thday  
after an operation. Euthanasia was carried out according to the Provisions of ISO 10993-2-2011 under the  
general anesthesia. An analysis of macroscopic picture of the abdominal cavity was made at the dissection of  
animals after euthanasia.  
For the making the morphological preparations ready the investigated area of liver was excised and fixed  
in 10% solution of neutral for malin. After expiration of the fixing terms bioptate was inundated by paraffin in a  
shape of blocks. Series of sections with a thickness of three-four µm were made. Histological preparations were  
painted by hematoxylin and eosin. For the estimation of histological changes in liver a system of points was  
employed in accordance with ISO 10993-6-2011 where the parameters of semi-quantitative estimation of the  
number and distribution of cells characterizing the inflammatory process (polymorphonuclear neutrophils,  
lymphocytes, plasmatic cells, macrophages, eosinophils and multinuclear cells) were taken into account. At the  
microscopy the dynamics of the inflammatory reaction’s development, features of the liver’s parenchyma  
regeneration as well as the degree of the investigated implant’s destruction were estimated.  
Experimental studies had been undertaken with the observance of the rules accepted by the European  
convention for the protection of vertebrate animals used for experimental and other scientific purposes (ETS N  
123), Strasbourg, 18.03.1986. The obtained results were subjected to the statistical processing with the using the  
standard package of Microsoft Excel 2010software by the method of variation statistics with the estimation of  
indexes’ values (M±m) and distinctions of the examined selections on the Student’s t-criterion. Distinctions in  
the compared groups were considered reliable at the level of value 95% (P<0.05).  
Ethical approval  
The review board and ethics committee of RSCS named after acad. V.Vakhidov approved the study  
protocol and informed consents were taken from all the participants. Study protocol as well as the study itself  
was approved.  
To cite this paper: Ismailov BA, Sadykov RA, and Mirzaahmedov BM. 2019. Comparative efficacy of the hemostatic implant made of the cellulose derivatives on  
the model of parenchymatous hemorrhage from liver. J. Life Sci. Biomed. 9(1): 34-41-; www.jlsb.science-line.com  
RESULTS AND DISCUSSION  
An active parenchymatous bleeding was being marked in a formed wound of liver. In a basic group at the using  
Heprocel hemostasis started during 34.0±2.5 seconds (Picture 1), in a control group with the using the  
application hemostatic material Sergicel® FibrillarTM the time of the stopping the bleeding made up 69.5±5.5  
seconds (Picture 2). At the 10-minutes supervision a renewal in bleeding was observed in a basic group in two  
(5%) cases, and in a control – in eight (22.2%) cases.  
It was noted that after application of hemostatic preparation Heprocel the wound surface due to its high  
hygroscopic it remained dry, while at the using the application hemostatic material Sergicel® FibrillarTM  
a
seepage of blood between fibers with the continuing bleeding reaching the friable hemostasis had been marked  
(Picture 2). The results of experimental researches on the achievement of hemostasis were presented in table 1.  
The obtained results showed a reliable (P<0.05) distinction in the shortening the time of the hemorrhage  
stopping and the blood loss at the using the hemostatic implant Heprocel with respect to the indexes of  
Sergicel® FibrillarTM . In the fixed terms animals were subjected to euthanasia and an intake of material for the  
conducting the morphological estimation had been carried out. After the first day an expressed inflammatory  
reaction and adhesive process had not been marked in the abdominal cavity (Picture 3). A vacuolar dystrophy of  
hepatocytes with expansion of sinusoidal spaces was marked microscopically subcapsularly (Picture 5). The  
amount of elements of inflammation in visual field made up as follows: polymorphonuclear- three, lymphocytes-  
four, plasmatic cells- three, macrophages- two. Necrosis zone – 500 µm (Picture 4).  
On the seventh day of the experiment pellicle coverage of a pellucid-whitishcolor had been formed in an  
abdominal cavity on the front surface of liver in the area of lesion. With thata formation of the adhesive process  
was not found (Picture 5). Fibrosis of the liver’s capsule was microscopically marked with the reducingof the  
inflammatory infiltrate which was expressed in the form of reduction in amount: polymorphonuclear- two,  
lymphocytes- three, plasmatic cells- three, macrophages- two. Necrosiszone- 200 µm. Neovascularization -  
three. Signs of debris (Heprocel) (Picture 6).  
On the 14th day of the experiment a moderate-mildadhesive process was marked in an abdominal cavity.  
There was a thin pellucid coverage on the surface of liver (Picture 7). Strengthening of regenerator processes  
was microscopically marked in a parenchyma, especially in a zone of lesion which was manifested as a  
restoration of the frameconstruction of liver, disappearance of edema and plethora, reduction in thickness of  
fibrotic pellicle of liver up to 100 µm. A moderate lymphoid infiltration of the capsule of liver was marked with  
reduction in visual fieldin an amount: polymorphonuclear- three, lymphocytes- three, plasmatic cells- three,  
macrophages- two. Necrosiszone- null. Neovascularization- one, fibrosis- two, fatty infiltration - one. Signs of  
debris (Heprocel) were determined (Picture 8).  
On the 30thday of the experiment a calming down of the adhesive process was noted in an abdominal  
cavity. The surface of liver was smooth and of a soft consistency, without the signs of inflammation (Picture 10).  
A reduction in thickness of fibrotic pellicle, decrease in amount of elements of inflammatory character (singular  
amount of lymphocytes) were microscopically marked. Singular elements of debris (Picture 11).  
Picture 1. Stopping the bleeding from the wound of  
liver with the help of hemostatic Heprocel powder  
Picture 2. Application of hemostatic material  
Sergicel® FibrillarTM  
To cite this paper: Ismailov BA, Sadykov RA, and Mirzaahmedov BM. 2019. Comparative efficacy of the hemostatic implant made of the cellulose derivatives on  
the model of parenchymatous hemorrhage from liver. J. Life Sci. Biomed. 9(1): 34-41-; www.jlsb.science-line.com  
Table 1. Indexes of the bleeding time at the modeling the experimental parenchymatous hemorrhage from the  
wound of liver in rats  
Repeated  
hemorrhage, %  
Time of the hemorrhage  
stopping, seconds  
№
Groups  
n
P*  
ABS  
P-value*  
1
Comparative  
Basic  
36  
36  
69.5 ± 5.5  
34.0 ± 2.5  
-
2
8
5,6±3.9  
-
2
P<0.001  
22.2±7.0  
P<0.05  
P: an authenticity of the average values’ distinctions with respect to the comparative group (accounted with the use of the Student’s t-test).  
Picture 3. Macropictureon the first day after  
Picture 4. Tissue of liver in an area of Heprocel  
application of Heprocel.  
application on the first day. Light microscopy.  
Magnification x200, х400. Coloration Hematoxylin-Eosin.  
Picture 5. Macropicture on the seventh day after  
application of Heprocel. Formation of pellicle  
coverage.  
Picture 6. Tissue of liver in an area of Heprocel  
application on the seventh day. Light microscopy.  
Magnification x200, х400. Coloration Hematoxylin-Eosin.  
Picture 7. Macropicture on the 14th day.  
Application of Heprocel, the inning of pellicle  
coverage.  
Picture 8. Tissue of liver in an area of Heprocel  
application on the 14th day. Absence of necrosis  
zone. Light microscopy. Magnification x200, х400.  
Coloration Hematoxylin-Eosin.  
To cite this paper: Ismailov BA, Sadykov RA, and Mirzaahmedov BM. 2019. Comparative efficacy of the hemostatic implant made of the cellulose derivatives on  
the model of parenchymatous hemorrhage from liver. J. Life Sci. Biomed. 9(1): 34-41-; www.jlsb.science-line.com  
Picture 9. Macropicture on the 30th day. Entire  
Picture 10. Tissue of on the 30th day. Singular  
degradation of the hemostatic implant Heprocel.  
elements of Heprocel. Light microscopy.  
Magnification x200, х400. Coloration Hematoxylin-Eosin.  
Expressed pathohistological changes in the tissue of liver were not found. The capsule of liver was not  
incrassated, contained the longitudinally oriented bunches of collagen fibers. Interlobular connecting tissue  
was developed poorly, and signs of inflammatory infiltration and fibrosis of liver were not detected.  
Hepatocytes of polygonal form with a centrally located nucleus, frequently a nucleolus was determined. Quite  
often binuclear hepatocytes occurred. Sinusoid capillaries were of ordinary sizes. Singular erythrocytes and  
leucocytes were determined in a lumen. In the wall of sinusoid hemocapillaries and Disse spaces singular  
Kupffer cells having an intact structure were revealed at a large magnification. A moderate dilation and blood  
filling of sinusoid hemocapillaries, central and under lobular veins were noted in some cases. An endothelial  
lining was without destructive changes, in some places swelled endotheliocytes with hyperchromic nucleus  
were marked. The structure of cholangiolandinter lobular biliary ducts was without pathological changes. And  
all this pointed to the fact that the studied preparation did not influence the microscopic structures of liver  
negatively.  
In a comparison group a day after the applying the hemostatic material Sergicel® FibrillarTM a macroscopic  
picture showed a hemostatic material fully saturated with blood in the wound area and a formation of adhesive  
process with participation of an epiploon (Picture 11). Necrosis of hepatocytes, edema of sinusoids, plethora of  
vessels were microscopically marked (Picture 12). The quantitative index of inflammatory process showed:  
polymorphonuclear- one, lymphocytes - one, plasmatic cells - one. Necrosis zone -100 µm. Neovascularization –  
one, fibrosis - one. Debris-plasts.  
On the seventh day of the experiment on the surface of the liver’s wound a preservation of structure of  
hemostatic material Sergicel® FibrillarTM was noted by the formation of an adhesive process with the involving  
of nearby organs (Picture 13). Microscopically fibers of Sergicel® FibrillarTM were abundantly infiltrated by  
neutrophil leucocytes, a preservation of hemorrhage, edema of sinusoids, and plethora were marked (Picture  
14). The frame structure of liver was destroyed, and the focuses of coagulative necrosis were marked.  
Quantitative index of the inflammation elements: polymorphonuclear-three, lymphocytes- three, plasmatic cells  
- three, macrophages - one. Necrosis zone- 220 µm. Neovascularization- one, fibrosis–two. Debris-plasts.  
On the 14thday on the hepatic wound’s surface it was marked a continuation of the preservation of  
hemostatic material Sergicel® FibrillarTM fully wrapped up by an epiploon, an expressed inflammatory reaction  
with development of massive adhesive process took place from the side of abdominal cavity (Picture 15). An  
excrescence of granulation tissue rich in blood vessels with a negligible quantity of collagen fibers was  
microscopically marked (Picture 16). There was a strengthening of fatty infiltration. Quantitatively a  
composition of inflammatory elements made up: polymorphonuclear- three, lymphocytes- three, plasmatic cells  
- two, macrophages- one, giant cell - one. Neovascularization- two, fibrosis- two, fatty infiltrate- four. Debris-  
plasts.  
On the 30thday of the experiment on the surface of the liver’s wound a reduction in sizes of hemostatic  
material Sergicel® FibrillarTM are with the preservation of adhesive process were marked (Picture 17).  
A
quantitative reduction in elements of inflammation was also marked microscopically: polymorphonuclear- two,  
lymphocytes- two, plasmatic cells- one, macrophages- one. Neovascularization- one, fibrosis- two. Debris-plasts  
(Picture 18).  
To cite this paper: Ismailov BA, Sadykov RA, and Mirzaahmedov BM. 2019. Comparative efficacy of the hemostatic implant made of the cellulose derivatives on  
the model of parenchymatous hemorrhage from liver. J. Life Sci. Biomed. 9(1): 34-41-; www.jlsb.science-line.com  
Picture 11. The first day. Hemostatic material Surgicel  
fibrillar, adhesive process with involving the epiploon and  
small intestine.  
Picture 12. Tissue of liver on the first day. Application of  
Surgicel fibrillar, saturation with neutrophil leucocytes.  
Necrosis of hepatocytes, presence of debris. Light  
microscopy.  
Magnification  
x200,  
х400.  
Coloration  
Hematoxylin-Eosin.  
Picture 13. The seventh day. Hemostatic material  
Sergicel® FibrillarTM, formation not adhesive process  
with involving the small intestine and stomach.  
Picture 14. Tissue of liver on the seventh day. Application  
of Sergicel® FibrillarTM. Preservation of plethora and  
edema of sinusoids. Presence of debris. Light microscopy.  
Magnification x200, х40. Coloration Hematoxylin-Eosin.  
Picture 15. The 14th day. Hemostatic material Sergicel®  
Picture 16. Tissue of liver on the 14th day. Application of  
Sergicel® FibrillarTM, excrescence of granulation tissue,  
fatty infiltration. Presence of debris. Light microscopy.  
Magnification x200, х40.Coloration Hematoxylin-Eosin.  
FibrillarTM, formation of massive adhesive process  
Picture 17. The 30th day. Reduction in sizes of hemostatic  
materialSurgicelfibrillar.  
Picture 18. Tissue of liver on the 30th day. Fragmentation  
of fibers of Surgicel fibrillar. Light microscopy.  
Magnification x200, х400.Coloration Hematoxylin-Eosin.  
To cite this paper: Ismailov BA, Sadykov RA, and Mirzaahmedov BM. 2019. Comparative efficacy of the hemostatic implant made of the cellulose derivatives on  
the model of parenchymatous hemorrhage from liver. J. Life Sci. Biomed. 9(1): 34-41-; www.jlsb.science-line.com  
At the macroscopic evaluation the structure of the application hemostatic material Sergicel® FibrillarTM  
was preserved up to 30 days. Using the application hemostatic material Sergicel® FibrillarTM promoted the  
development to inflammatory reaction, on the 14thday after an operation an expressed adhesive process of the  
abdominal cavity was marked with the involving the nearby organs which began to calm down on 30thday. On  
the same day an expressed biodegradation of Surgicel fibrillary began, a preparation disintegrated on  
fragments and was phagocyted bymacrophages, and here a number of inflammatory elements diminished.  
As a result of researches it is possible to come to conclusion that a hemostatic implant Heprocel causes  
on the first day a morphological reaction of liver in a kind of inflammation and excrescence of the connecting  
tissue, but these processes calm down quickly. An inflammatory reaction is less expressed than in the group of  
control. To the 30thday in a basic group after application of Heprocel a biodecomposition of hemostatic implant  
is marked, and regenerator processes in the parenchyma of liver, especially in a zone of lesion, were observed  
that testifies to the restoration of the liver’s tissue, while in a comparative group an active degradation of  
application hemostatic material began on the 30th day an dan expressed adhesive process took place in an  
abdominal cavity.  
CONCLUSION  
Thus, the results of the conducted research of the comparative efficiency showed that the created implant  
Heprocel comparable with a foreign analogue differed by a greater hemostatic activity, good adhesiveness to  
the parenchyma of liver. In in vivo researches it was marked that the acceleration of the blood coagulability’s  
time had been by as many as two times faster than in the comparative group. From the data of our researches  
hemostatic powder closely adjoins the tissue of liver, stops the bleeding, cases of relapse of bleeding were not  
marked. Histological researches conducted in the dynamics of the healing the wounds of liver revealed that  
Heprocel did not cause the expressed inflammatory reaction, the zone of lesion did not exceed 150 µm, bio-  
decomposition started after 14 days.  
DECLARATIONS  
Acknowledgements  
This work was supported by “Republican Specialized Scientific and Practical Medical Center of Surgery  
named after Academician V.Vakhidov”, Uzbekistan.  
Authors’ contributions  
All authors contributed equally to this work.  
Competing interests  
The authors declare that they have no competing interests.  
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To cite this paper: Ismailov BA, Sadykov RA, and Mirzaahmedov BM. 2019. Comparative efficacy of the hemostatic implant made of the cellulose derivatives on  
the model of parenchymatous hemorrhage from liver. J. Life Sci. Biomed. 9(1): 34-41-; www.jlsb.science-line.com  
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To cite this paper: Ismailov BA, Sadykov RA, and Mirzaahmedov BM. 2019. Comparative efficacy of the hemostatic implant made of the cellulose derivatives on  
the model of parenchymatous hemorrhage from liver. J. Life Sci. Biomed. 9(1): 34-41-; www.jlsb.science-line.com