Application of chitosan-based wound dressings in local treatment of parenchymal organ wounds: a preclinical experimental study

Background. Injuries of various origins with damage to parenchymal organs remain one of the urgent issues of emergency surgery, despite all the achievements of medical science of the first quarter of the XXI century. One way to improve the quality of treatment for patients with this pathology consists in developing new wound dressings or modifying the properties of existing ones. Hemostatic efficacy is claimed to be one of the main requirements for such dressings.

Objective. To perform a comparative analysis of the efficacy of the developed biodegradable wound dressings based on chitosan in the treatment of experimental wounds of parenchymal organs.

Methods. The study involved laboratory animals (male rabbits weighing 2900 ± 150 g) to form experimental wounds of parenchymatous organs. The methodology involved wounding the liver via internal method, with the creation of a tissue defect of a given volume, or forming a linear incised wound with fixed parameters followed by application of a developed wound dressing. In the control group of animals, a collagen hemostatic sponge was used as a wound dressing. The animals used in the experiment were kept in accordance with GOST 33044-2014 “Principles of good laboratory practice”. The experiment involved studying the properties of two samples of wound dressings developed on the basis of modified Chitosan Soft (Ch-S) and Chitosan Hard (Ch-H) chitosan, having different properties due to their different structural parameters. The applied ultrasound control of the experimental wound area, with visualization of the samples of the investigated material in the process of biodegradation, enabled the features of the wound process to be studied in more detail. Statistical processing of the study results was carried out by methods of variational statistics, including the calculation of mean values (M), standard errors of mean values (± m). The criterion of the level of statistical significance considered a value of p <0.05. Histomorphological examination of samples was carried out using classical methods.

Results. An experimental study conducted on laboratory animals in the treatment of liver wounds, followed by a comprehensive assessment of the results obtained, revealed high efficacy in the developed wound dressings in comparison with the control. The following parameters predicted in the development of wound dressing samples were confirmed: stable hemostatic and scaffold functions, biodegradability, adhesiveness and stimulating effect on bioreparative processes in the wound area. In addition, the ultrasound control algorithm in vivo was adapted in animals to assess the dynamics of the wound process and biodegradation of the studied wound dressings in wounds of parenchymal organs in the experiment, previously used in studying the dynamics of the wound process in soft tissues.

Conclusion. The developed samples of chitosan-based wound dressings proved their efficacy in an experimental model of the wound process in parenchymal organs. The applied ultrasonic method for monitoring the biodegradation of the studied wound dressing, as well as the dynamics of the wound process in the liver tissue, revealed the correspondence between the visualized image and the histomorphological picture of the studied tissues, the structure and properties of the wound dressing.

1. Parkhisenko YA, Vorontsov AK, Cherednikov EF, Barannikov SV, Korsakov AV, Troshin VP. Morphological assessment of reparative regeneration of experimental bleeding liver wounds in the treatment of hemostatic agent Surgitamp and granular sorbent Molselect G-50. Journal of Volgograd State Medical University. 2023;20(1):73–80 (In Russ.). https://doi.org/10.19163/1994-9480-2023-20-1-73-80

2. Gavrilyuk VP, Lipatov VA, Mikhaylov KA, Severinov DA. Evaluation of the dynamics of blood loss indicators when using new samples of local hemostaptic agents after liver injury in the in vivo experiment. Polytrauma. 2022;1:84–89 (In Russ.). https://doi.org/10.24412/1819-1495-2022-1-84-89

3. Kulagin VI, Batik EV, Andreev MI, Mollaev ES. The long-term result of the “diverticulization” off the duodenum (zemlyanoy procedure) for the complications of parafaterial diverticulum. The Journal of Emergency Surgery named after I.I. Dzhanelidze. 2022;4(9):55–59 (In Russ.). https://doi.org/10.54866/27129632_2022_4_55

4. Pacheco M, Barros AA, Aroso IM, Autorino R, Lima E, Silva JM, Reis RL. Use of hemostatic agents for surgical bleeding in laparoscopic partial nephrectomy: Biomaterials perspective. J Biomed Mater Res B Appl Biomater. 2020;108(8):3099–3123. https://doi.org/10.1002/jbm.b.34637

5. Ruscelli P, Gemini A, Rimini M, Santella S, Candelari R, Rosati M, Paci E, Marconi V, Renzi C, Commissari R, Cirocchi R, Santoro A, D’Andrea V, Parisi A. The role of grade of injury in non-operative management of blunt hepatic and splenic trauma: Case series from a multicenter experience. Medicine (Baltimore). 2019;98(35):e16746. https://doi.org/10.1097/MD.0000000000016746

6. Afifi I, Abayazeed S, El-Menyar A, Abdelrahman H, Peralta R, AlThani H. Blunt liver trauma: a descriptive analysis from a level I trauma center. BMC Surg. 2018;18(1):42. https://doi.org/10.1186/s12893-0180369-4

7. Gönültaş F, Kutlutürk K, Gok AFK, Barut B, Sahin TT, Yilmaz S. Analysis of risk factors of mortality in abdominal trauma. Ulus Travma Acil Cerrahi Derg. 2020;26(1):43–49. https://doi.org/10.14744/tjtes.2019.12147. PMID: 31942731

8. Mehta N, Babu S, Venugopal K. An experience with blunt abdominal trauma: evaluation, management and outcome. Clin Pract. 2014;4(2):599. https://doi.org/10.4081/cp.2014.599

9. Swaid F, Peleg K, Alfici R, Matter I, Olsha O, Ashkenazi I, Givon A; Israel Trauma Group; Kessel B. Concomitant hollow viscus injuries in patients with blunt hepatic and splenic injuries: an analysis of a National Trauma Registry database. Injury. 2014;45(9):1409–1412. https://doi.org/10.1016/j.injury.2014.02.027

10. Severinov DA, Bondarev GA, Lipatov VA, Saakyan AR. Intraoperative Tactics of Local Surgical Hemostasis in Injuries and Planned Operations on the Parenchymal Organs of the Abdominal Cavity. Journal of Experimental and Clinical Surgery. 2020;13(3):268–278. https://doi.org/10.18499/2070-478X-2020-13-3-268-278

11. Chrysou K, Halat G, Hoksch B, Schmid RA, Kocher GJ. Lessons from a large trauma center: impact of blunt chest trauma in polytrauma patients-still a relevant problem? Scand J Trauma Resusc Emerg Med. 2017;25(1):42. https://doi.org/10.1186/s13049-017-0384-y

12. Gavrishuk YV, Manukovskiy VA, Tulupov AN, Demko AE, Kolchanov EA, Savello VE, Kandyba DV, Kazhanov IV, Platonov SA, Kazankin AS. Possibilities of non-operative and minimally invasive organ-preserving spleen injuries management in blunt abdominal injuries in adults. Grekov’s Bulletin of Surgery. 2021;180(4):18–27 (In Russ.). https://doi.org/10.24884/0042-4625-2021-180-4-18-27

13. Rotkin EA, AgalaryanAKh, Agadzhanyan VV. Features of diagnostics and treatment of injuriesto parenchymatous abdominal organs in polytrauma. Polytrauma. 2023;1:29–33 (In Russ.). https://doi.org/10.24412/1819-1495-2023-1-29-33

14. Lipatov VA, Denisov AA, Petrosyan SE, Klimenko AE, Panov AA, Bobrovskaya EA. Evaluation of the effectiveness of two-component sponge hectopative agents in acute in vivo experiment. Humans and their health. 2022;25(4):5–10 (In Russ.). https://doi.org/10.21626/vestnik/2022-4/01

15. Manukovsky VA, Gavrishchuk YaV, Tulupov AN, Demko AE, Savello VE, Kandyba DV, Kolchanov EA Possibilities of conservative and minimally invasive treatment of blunt injury to parenchymal abdominal organs in adults. Polytrauma. 2022;3:21–33 (In Russ.). https://doi.org/10.24412/1819-1495-2022-3-21-33

16. Nijdam TMP, Spijkerman R, Hesselink L, Leenen LPH, Hietbrink F. Predictors of surgical management of high grade blunt splenic injuries in adult trauma patients: a 5-year retrospective cohort study from an academic level I trauma center. Patient Saf Surg. 2020;14:32. https://doi.org/10.1186/s13037-020-00257-3

17. Bondarev G.A., Lipatov V.A., Severinov D.A., Saakyan A.R. Intraoperative Tactics of Local Surgical Hemostasis in Injuries and Planned Operations on the Parenchymal Organs of the Abdominal Cavity. Journal of experimental and clinical surgery. 2020;13(3):268– 278 (In Russ.). https://doi.org/10.18499/2070-478X-2020-13-3-268-278

18. Maystrenko A.N., Bezhin A.I., Lipatov V.A., Chizhikov G.M. Determination of blood loss volume in modeling injuries of parenchymatous organs with application of new hemostatic agents in an experiment. INNOVA. 2018;2(11);12–14 (In Russ.). https://doi.org/10.21626/innova/2018.2/03

19. Oltarzhevskaya ND, Korovina MA, Krichevsky GE, Shchedrina MA, Egorova EA. The opportunities of using polysaccharides for the wound treatment. Wounds and wound infections. The prof. B.M. Kostyuchenok journal. 2019;6(2):24–31 (In Russ.). https://doi.org/10.25199/2408-96132019-6-2-24-31

20. Mokhov EM, Lyubskij IV, Sergeev АN, Morozov АM, Kadykov VА, Аskerov EHM., Peltikhina OV, Khorak KI. The Opportunities for Developing a New Biologically Active Suture Material in Surgery. Journal of experimental and clinical surgery. 2019;12(3):193–198 (In Russ.). https://doi.org/10.18499/2070-478X-2019-12-3-193-198

21. Singh R, Shitiz K, Singh A. Chitin and chitosan: biopolymers for wound management. Int Wound J. 2017;14(6):1276–1289. https://doi.org/10.1111/iwj.12797

22. Nasef SM, Khozemy EE, Kamoun EA, El-Gendi H. Gamma radiation-induced crosslinked composite membranes based on polyvinyl alcohol/chitosan/AgNO3/vitamin E for biomedical applications. Int J Biol Macromol. 2019;137:878–885. https://doi.org/10.1016/j.ijbiomac.2019.07.033

23. Liu H, Wang C, Li C, Qin Y, Wang Z, Yang F, Li Z, Wang J. A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing. RSC Adv. 2018;8(14):7533– 7549. https://doi.org/10.1039/c7ra13510f. PMID: 35539132; PMCID: PMC9078458

24. Ushmarov DI, Gumenyuk SE, Gumenyuk AS, Gayvoronskaya TV, Karablina SY, Pomortsev АV, Sotnichenko AS, Melkonyan KI, Grigoriev TЕ. Comparative evaluation of chitosan-based multifunctional wound dressings: a multistage randomised controlled experimental trial. Kuban Scientific Medical Bulletin. 2021;28(3):78–96 (In Russ.). https://doi.org/10.25207/1608-6228-2021-28-3-78-96