Multicomponent coating in purulent wound healing: A randomised controlled experimental study
https://doi.org/10.25207/1608-6228-2021-28-2-16-32
Abstract
Background. Purulent wound healing is a pressing surgical challenge relevant in 30−35% of patient cases. To the more, wound infectious agents elaborate resistance to available drugs warranting the development of new drug combinations exserting a multidirectional effect on the wound process.
Objective. Using a purulent wound model to experimentally evaluate the efficiency of a new multicomponent wound coating comprised of polyethylene oxide and carboxymethylcellulose sodium-immobilised dioxidine, methyluracil, metronidazole and lidocaine hydrochloride in comparison with a legal approved wound coating drug preparation of beeswax and propolis-based dioxidine ointment.
Methods. The antimicrobial activity range (disk-diffusion method) and local anaesthetic effect (Rainier’s method) of the developed wound coating have been assessed. The healing process was studied in a purulent wound model with 72 Wistar rats divided between two equal groups. The following methods were applied: visual wound inspection (wound cleansing time, absence of wound-surrounding tissue oedema, granulation and epithelisation), planimetric parameter estimation (wound area, healing rate, wound area reduction ratio), wound contamination and pH measurement, wound section cell morphometry (granulocyte, macrophage, lymphocyte and fibroblast counts, cell index estimation). Daily dressings were applied for 15 days.
Results. The developed wound coating exhibited high efficiency against Gram-positive and Gram-negative bacteria in the zone of inhibition tests. Its local anaesthetic effect was significantly superior to the approved drug by the duration of action. The wound area reduction was 94.2 (93.7; 94.8)% in the experimental group and 86 (84.2; 88.8)% in the control (differences statistically significant) already on day 10. A maximal healing rate in both groups was registered in phase 1 of the wound process being 1.4 times higher in experiment compared to the control. The wound contamination was significantly lower in experiment vs. control on day 8 (p = 0.0075). Wound pH negatively correlated with the fibroblast count and positively — with the contamination level.
Conclusion. The study demonstrates high efficiency of the developed wound coating against infectious agents and its positive healing impact via reducing phase 1 and stimulating proliferation in phase 2 of the wound process.
About the Authors
A. Yu. GrigoryanRussian Federation
Arsen Yu. Grigoryan — Cand. Sci. (Med.), Assoc. Prof., Chair of Operative Surgery and Topographic Anatomy
Karla Marksa str., 3, Kursk, 305041
+7 (471) 258-81-42, +7 (920) 267-51-97
A. I. Bezhin
Russian Federation
Alexander I. Bezhin — Dr. Sci. (Med.), Prof., Head of the Chair of Operative Surgery and Topographic Anatomy
Karla Marksa str., 3, Kursk, 305041
T. A. Pankrusheva
Russian Federation
Tatiana A. Pankrusheva — Dr. Sci. (Pharm.), Prof., Head of the Chair of Pharmaceutical Technology
Karla Marksa str., 3, Kursk, 305041
M. S. Chekmareva
Russian Federation
Marina S. Chekmareva — Cand. Sci. (Pharm.), Assoc. Prof., Chair of Pharmaceutical Technology
Karla Marksa str., 3, Kursk, 305041
L. V. Zhilyaeva
Russian Federation
Lyudmila V. Zhilyaeva — Cand. Sci. (Med.), Senior Lecturer, Chair of Microbiology, Virology and Immunology
Karla Marksa str., 3, Kursk, 305041
E. S. Mishina
Russian Federation
Ekaterina S. Mishina — Cand. Sci. (Med.), Assoc. Prof., Chair of Histology, Embryology and Cytology
Karla Marksa str., 3, Kursk, 305041
References
1. Оrlov A.G., Lipin A.N., Kozlov K.L. Treatment of chronic wounds — literature reviev. Kuban Scientific Medical Bulletin. 2016; (5): 147–153 (In Russ., English abstract). DOI: 10.25207/1608-6228-2016-5-147-153
2. Han G., Ceilley R. Chronic wound healing: a review of current management and treatments. Adv. Ther. 2017; 34(3): 599–610. DOI: 10.1007/s12325-017-0478-y
3. Burnham J.P., Kollef M.H. Treatment of severe skin and soft tissue infections: a review. Curr. Opin. Infect. Dis. 2018; 31(2): 113–119. DOI: 10.1097/QCO.0000000000000431
4. Golan Y. Current treatment options for acute skin and skin-structure infections. Clin. Infect. Dis. 2019; 68(Suppl 3): S206–S212. DOI: 10.1093/cid/ciz004
5. Gidirim G., Prisekaru I., Bogyan G., Glavan N. Clinical results of treatment of purulent wounds of skin and soft tissues with the antiseptic “Isofural” (solution). Medical almanac. 2018; 4(55): 114–116 (In Russ., English abstract). DOI: 10.21145/2499-9954-2018-4-114-116
6. Balin V.N., Karshiyev H.K., Muzykin M.I., Iordanishvili A.K. Endogenic intoxication in various methods of managing widespread phlegmons (pre-clinical trial). Kurskii Nauchno-Prakticheskii Vestnik “Chelovek i Ego Zdorov’e”. 2017; 1: 77–80 (In Russ., English abstract). DOI: 10.21626/vestnik/2017-1/14
7. Katorkin S.E., Bystrov S.A., Lisin O.E., Rozanova A.A., Bezborodov A. I. Evaluation of the efficacy of modern wound care dressings in the complex treatment of purulent wounds. Ambulatornaya Khirurgiya. 2019; 1–2: 146–152 (In Russ., English abstract). DOI: 10.21518/1995-1477-2019-1-2-146-152
8. Arkhipov D.V., Andreev A.A., Atyakshin D.A., Glukhov A.A., Ostroushko A.P. Inkjet oxygen-sorption treatment in local treatment purulent soft tissue wounds. Journal of Experimental and Clinical Surgery. 2020; 13(1): 41–45 (In Russ., English abstract). DOI: 10.18499/2070-478X-2020-13-1-41-45
9. Razmakhnin E.V., Shangin V.A., Kudryavtseva O.G., Okhlopkov D.Y. Possibilities of vacuum-instillation therapy with dimexidum and betadine in the treatment of purulent wounds. Acta Biomedica Scientifica (East Siberian Biomedical Journal). 2017; 2(6): 153–156 (In Russ., English abstract). DOI: 10.12737/article_5a0a8e0d03dc42.56682733
10. Kamamoto F., Lima A.L.M., Rezende M.R., Mattar-Junior R., Leonhardt M.C., Kojima K.E., Santos C.C.D. A new low-cost negative-pressure wound therapy versus a commercially available therapy device widely used to treat complex traumatic injuries: a prospective, randomized, non-inferiority trial. Clinics (Sao Paulo). 2017; 72(12): 737–742. DOI: 10.6061/clinics/2017(12)04
11. Shukla S.K., Sharma A.K., Gupta V., Yashavarddhan M.H. Pharmacological control of inflammation in wound healing. J. Tissue Viability. 2019; 28(4): 218–222. DOI: 10.1016/j.jtv.2019.09.002
12. Neff J.A., Bayramov D.F., Patel E.A., Miao J. Novel antimicrobial peptides formulated in chitosan matrices are effective against biofilms of multidrug-resistant wound pathogens. Mil. Med. 2020; 185(Suppl 1): 637–643. DOI: 10.1093/milmed/usz222
13. Hoffmann J.P., Friedman J.K., Wang Y., McLachlan J.B., Sammarco M.C., Morici L.A., Roy C.J. In situ treatment with novel microbiocide inhibits methicillin resistant Staphylococcus aureus in a murine wound infection model. Front. Microbiol. 2020; 10: 3106. DOI: 10.3389/fmicb.2019.03106
14. Starr C.G., Ghimire J., Guha S., Hoffmann J.P., Wang Y., Sun L., Landreneau B.N., Kolansky Z.D., Kilanowski-Doroh I.M., Sammarco M.C., Morici L.A., Wimley W.C. Synthetic molecular evolution of host cell-compatible, antimicrobial peptides effective against drug-resistant, biofilm-forming bacteria. Proc. Natl. Acad. Sci. USA. 2020; 117(15): 8437–8448. DOI: 10.1073/pnas.1918427117
15. Baron J.M., Glatz M., Proksch E. Optimal support of wound healing: new insights. Dermatology. 2020; 236(6): 593–600. DOI: 10.1159/000505291
16. Nethi S.K., Das S., Patra C.R., Mukherjee S. Recent advances in inorganic nanomaterials for wound-healing applications. Biomater. Sci. 2019; 7(7): 2652–2674. DOI: 10.1039/c9bm00423h
17. Silina E.V., Manturova N.E., Vasin V.I., Artyushkova E.B., Khokhlov N.V., Ivanov A.V., Stupin V.A. Efficacy of A Novel Smart Polymeric Nanodrug In The Treatment Of Experimental Wounds In Rats. Polymers (Basel). 2020; 12(5): 1126. DOI: 10.3390/polym12051126
18. Fakayode O.J., Tsolekile N., Songca S.P., Oluwafemi O.S. Applications of functionalized nanomaterials in photodynamic therapy. Biophys. Rev. 2018; 10(1): 49–67. DOI: 10.1007/s12551-017-0383-2
19. Bystrov S.A., Bezborodov A.I., Katorkin S.E. Treatment of purulent wounds with wound dressing on a foamy basis with hydrofiber technology. Khirurgiya. Zhurnal im. N.I. Pirogova. 2017; 7: 49–53 (In Russ., English abstract). DOI: 10.17116/hirurgia2017749-53
20. Abrahamian F.M., Sakoulas G., Tzanis E., Manley A., Steenbergen J., Das A.F., Eckburg P.B., McGovern P.C. Omadacycline for acute bacterial skin and skin structure infections. Clin. Infect. Dis. 2019; 69(Suppl 1): S23–S32. DOI: 10.1093/cid/ciz396
21. De Silva C.C., Israni N., Zanwar A., Jagtap A., Leophairatana P., Koberstein J.T., Modak S.M. “Smart” polymer enhances the efficacy of topical antimicrobial agents. Burns. 2019; 45(6): 1418–1429. DOI: 10.1016/j.burns.2019.04.013
22. Schilcher K., Horswill A.R. Staphylococcal biofilm development: structure, regulation, and treatment strategies. Microbiol. Mol. Biol. Rev. 2020; 84(3): e00026–19. DOI: 10.1128/MMBR.00026-19
23. Li T., Wang G., Yin P., Li Z., Zhang L., Tang P. Adaptive expression of biofilm regulators and adhesion factors of Staphylococcus aureus during acute wound infection under the treatment of negative pressure wound therapy in vivo. Exp. Ther. Med. 2020; 20(1): 512–520.
24. Shevelev A.B., La Porta N., Isakova E.P., Martens S., Biryukova Y.K., Belous A.S., Sivokhin D.A., Trubnikova E.V., Zylkova M.V., Belyakova A.V., Smirnova M.S., Deryabina Y.I. In vivo antimicrobial and wound-healing activity of Resveratrol, Dihydroquercetin, and Dihydromyricetin against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Pathogens. 2020; 9(4): 296. DOI: 10.3390/pathogens9040296
25. Lindsay S., Oates A., Bourdillon K. The detrimental impact of extracellular bacterial proteases on wound healing. Int. Wound J. 2017; 14(6): 1237–1247. DOI: 10.1111/iwj.12790
26. Oltarzhevskaya N.D., Korovina M.A., Krichevsky G.E., Shchedrina M.A., Egorova E.A. 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., English abstract). DOI: 10.25199/2408-9613-2019-6-2-24-31
27. Zakurdaev E.I., Chernyh A.V., Cherednikov E.F., Zakurdaeva M.P. Topographic-anatomic justification of various methods reducing tissue tension at prosthetic incisional hernia repair by “Sublay”. Journal of Experimental and Clinical Surgery. 2017; 10(1): 64–71. DOI: 10.18499/207-478X2017-10-1-64-71
Supplementary files
Review
For citations:
Grigoryan A.Yu., Bezhin A.I., Pankrusheva T.A., Chekmareva M.S., Zhilyaeva L.V., Mishina E.S. Multicomponent coating in purulent wound healing: A randomised controlled experimental study. Kuban Scientific Medical Bulletin. 2021;28(2):16-32. (In Russ.) https://doi.org/10.25207/1608-6228-2021-28-2-16-32