Biocompatibility and features of degradation of polymer anti-adjection membranes with antibacterial activity

When performing operations on the abdominal and thoracic organs, the main share of postoperative complications is represented by the formation of adhesions or the development of an infectious process, which leads to a decrease in the quality of life of patients, the need for reoperation and often causes deaths. A solution to this problem can be the use of intraoperative biodegradable anti-adhesion membranes that have their own antibacterial activity.

Aim. Development of polymer anti-adhesion membranes with their own anti-inflammatory and antibacterial activity, assessment of their biocompatibility and biodegradation in in vivo experiments

Materials and Methods. The membranes are made by electrospinning from a composition of biodegradable polymers: polylactide-co-glycolide copolymer (50:50) and polylactide-co-glycolide (85:15). To impart antibacterial properties to the membrane, the antibiotic Tigacil was added to the polymer solution in various dosages - 0.125; 0.25 and 0.5 mg/ml polymer solution. The antibacterial activity of the membranes in vivo was assessed. The physical and mechanical properties were studied and the surface structure of the membranes was assessed using a scanning electron microscope. Biocompatibility and dynamics of biodegradation were assessed in vivo by implantation into laboratory animals (rats) for periods of 14 days, 1, 2 and 3 months, followed by histological examination of explanted samples.

Results. Polymer membranes made by electrospinning, without the inclusion of Tigacil, consist of threads whose thickness was 1.63 microns (1.422.85 microns); when Tigacil is included in the fiber composition, the fiber thickness decreases to 1.2 microns (0.977 - 1.89 pm), while the threads are more densely and orderly located. The strength and elasticity modulus of membranes with Tigacil are almost 2 times higher than those of samples without the inclusion of the drug. The maximum antibacterial effect was achieved at a Tigacil dosage of 0.5 mg/ml - the zone of inhibition of Staphylococcus aureus at a Tigacil concentration of 0.125 mg/ ml was 146%, 0.25 mg/ml - 152% and at a concentration of 0.5 mg/ml - 11 .5 mm 177%. The inclusion of Tigacil led to a decrease in the rate of biodegradation of samples in vivo. The samples underwent biodegradation without signs of acute and chronic inflammation.

Conclusion. The inclusion of Tigacil in the membrane gives it antibacterial properties, and the optimal concentration of Tigacil was 0.5 mg/ml of the polymer solution. The inclusion of Tigacil in the polymer composition affects the morphology of the membranes, increases the strength and elastic modulus, which led to a decrease in the rate of degradation when implanted subcutaneously in rats. The absence of signs of inflammation confirms the biocompatibility of the developed membranes.

1. Profilaktika infekcij oblasti hirurgicheskogo vmeshatel'stva. Clinical guidelines N. Novgorod: Remedium Privolzh'e, 2018. 72 p. (in Russ).

2. Andreev AA, Ostroushko AP, Sotnikovа ES, Kiryanova DV, Britikov VN. Adhesive Disease of the Abdominal Cavity. Journal of experimental and clinical surgery. 2017;10(4):320-326. (in Russ). https://doi.org/10.18499/2070-478X-2017-10-4-320-326

3. Azoury SC, Norma EF, Qing LH, Kevin CS, Caitlin WH, Faris KA, Rodriguez-Unda NA, Poruk KE, Cornell P, Burce KK, Cooney CM, Nguyen HT, Eckhauser FE. Postoperative abdominal wound infection - epidemiology, risk factors, identification, and management. Chronic Wound Care Management and Research. 2015;2:137-148. https://doi.org/10.2147/CWCMR.S62514

4. Bockeria LA, Sivtsev VS. Postoperative pericardial adhesion: risk factors, pathogenesis and preventive methods. Annaly khirurgii. 2014;6:7-15. (in Russ).

5. ten Broek RP, Bakkum EA, Laarhoven CJ, van Goor H. Epidemiology and Prevention of Postsurgical Adhesions Revisited. Ann Surg. 2016;263(1):12-19. https://doi.org/10.1097/SLA.0000000000001286

6. Popov D. A. Postoperative infectious complications in cardiac surgery. Annals of Surgery (Russia) 2013;5:15-21. (in Russ).

7. Salminen JT, Mattila IP, Puntila JT, Sairanen HI. Prevention of postoperative pericardial adhesions in children with hypoplastic left heart syndrome. Interact Cardiovasc Thorac Surg. 2011;12(2):270-272. https://doi.org/10.1510/icvts.2010.241448

8. Markosyan SA, Lysyakov NM. Etiology, Pathogenesis and Prophylaxis of Adhesions in Abdominal Surgery. Surgery news. 2018;26(6):735-744. (In Russ). https://doi.org/10.18484/2305-0047.2018.6.735

9. Abdominal'naya khirurgicheskaya infektsiya : Rossiyskie natsion-al'nye rekomendatsii / BR Gel'fanda, AI Kirienko, NN Khachatryan, editors. 2nd ed. Moscow: Meditsinskoe informatsionnoe agentstvo, 2018. 168 p. (in Russ).

10. Aga E, Keinan-Boker L, Eithan A, Mais T, Rabinovich A, Nassar F. Surgical site infections after abdominal surgery: incidence and risk factors. A prospective cohort study. Infect Dis (Lond). 2015;47(11):761-767. https://doi.org/10.3109/23744235.2015.1055587

11. Cherniavskii AM, Tarkova AR, Ruzmatov TM, Morozov SV, Grigor'ev IA. Infections in cardiac surgery. Pirogov Russian Journal of Surgery. 2016;(5):64-68. (In Russ). https://doi.org/10.17116/hirurgia2016564-68

12. Jayakumar S, Khoynezhad A, Jahangiri M. Surgical Site Infections in Cardiac Surgery. Crit Care Clin. 2020;36(4):581-592. https://doi.org/10.1016/j.ccc.2020.06.006

13. Abakumov MM. Diagnosis and treatment of suppurative mediastinitis - a special chapter in the history of surgery. Pirogov Russian Journal of Surgery. 2019;3(1):105-110. (In Russ). https://doi.org/10.17116/hirurgia2019031105

14. Stepin AV. Etiology of the surgical site infection after open-heart surgery: single-center ten-year follow-up. RMJ. 2022;7:2-6. (in Russ).

15. Sahu MK, Siddharth B, Choudhury A, Vishnubhatla S, Singh SP, Menon R, Kapoor PM, Talwar S, Choudhary S, Airan B. Incidence, microbiological profile of nosocomial infections, and their antibiotic resistance patterns in a high volume Cardiac Surgical Intensive Care Unit. Ann Card Anaesth. 2016;19(2):281-287. https://doi.org/10.4103/0971-9784.179625.

16. Park CB, Suri RM, Burkhart HM, Greason KL, Dearani JA, Schaff HV, Sundt TM 3rd. Identifying patients at particular risk of injury during repeat sternotomy: analysis of 2555 cardiac reoperations. J Thorac Cardiovasc Surg. 2010;140(5):1028-1035. https://doi.org/10.1016/j.jtcvs.2010.07.086.

17. Head WT, Paladugu N, Kwon JH, Gerry B, Hill MA, Brennan EA, Kavarana MN, Rajab TK. Adhesion barriers in cardiac surgery: A systematic review of efficacy. J Card Surg. 2022;37(1):176-185. https://doi.org/10.1111/jocs.16062

18. Khromova VN. Postgospital'nye posleoperatsionnye oslozhneniya v abdominal'noy khirurgii. Izvestiya vysshikh uchebnykh zavedeniy. Povolzhskiy region. Meditsinskie nauki. 2011;2(18):128-135. (in Russ).

19. Rybakov KD, Sednev GS, Morozov AM, Ryzhova TS, Minakova YuYe. /Prevention of the formation of adhesions in the abdominal cavity (literature review)//Journal of New Medical Technologies. 2022;1:22-28. DOI: 10.24412/1609-2163-2022-1-22-28. (in Russ). https://doi.org/10.24412/1609-2163-2022-1-22-28.

20. Samartsev VA, Kuznetsova MV, Gavrilov VA, Kuznetsova MP, Par-shakov AA. Anticommissural barriers in abdominal surgery: up-to-date state of problem. Perm medical journal. 2017;XXXIV(2):87-93. (in Russ).

21. Shurygin MG, Shurygina IA. Prospects for prevention of adhesion process during cardiac surgical interventions. Acta Biomedica Scien-tifica. 2021;6(6-2):125-132. (In Russ). https://doi.org/101010.29413/ABS.2021-6.6-2.13

22. Mokhov EM, Sergeev AN. Implantation antimicrobial prevention of infection in the surgery intervention area. Siberian Medical Review. 2017;(3):75-81. (In Russ). https://doi.org/10.20333/2500136-2017-375-81

23. Nazarchuk AA, Vernygorodskyi SV, Palii VG, Nazarchuk GG. Experimental Reseach of Effectiveness of Antimicrobial Surgical Matherials Containing Decamethoxinum. Novosti Khirurgii. 2018;26(1):16-23 (In Russ). https://doi.org/10.18484/2305-0047.2018.1.16.