ANTI-ADHESIVE MEMBRANES FOR CARDIOVASCULAR SURGERY - EFFICACY EVALUATION IN A LARGE ANIMALS STUDY

Highlights

Formation of adhesions after chest surgery remains an unresolved issue. The use of biodegradable anti-adhesion membranes with anti-inflammatory activity can reduce the risk of adhesion. Preclinical assessment of the developed membranes in a large laboratory animal model is a mandatory step in the development of a medical device.

Aim. To conduct a preclinical evaluation of the effectiveness of an anti-adhesive biodegradable membrane with anti-inflammatory activity in a large laboratory animal model (sheep).

Methods. A composition of biodegradable polymers was used to manufacture the membranes: polylactide-co-glycolide copolymer (50:50) Mm 20–30 kDa and polylactide-co-glycolide (85:15). The polymers were dissolved in 1,1,1,3,3,3-hexafluoroisopropanol. To impart anti-inflammatory properties to the membrane, dexamethasone (DM) was added to the membrane composition at a final concentration of 1 mg DM/1 ml of polymer solution. The membranes were manufactured by electrospinning. The anti-adhesion efficiency of the membranes was assessed on an animal model (sheep) during implantation into the chest cavity.

Results. In the control group of animals, a massive adhesive process was noted. In the experimental group, six animals (66.6%) had no adhesions at all, two animals (22.2%) had weak adhesion of the lung and pericardium in the area of ​​membrane fixation with suture material, and one animal (11.1%) had moderate adhesion of the pericardium to the surface of the chest cavity.

Conclusion. The developed biodegradable membranes have demonstrated satisfactory anti-adhesive activity (88.8%). The implantation experience showed that it is better to use a membrane 30% larger in size than necessary to properly close the wound.

1. Bokeriya L.A., Milievskaya E.B., Pryanishnikov V.V., Orlov I.A. Serdechno-sosudistaya khirurgiya – 2022. Bolezni i vrozhdenny`e anomalii sistemy` krovoobrashheniya. Moscow:NMICz SSKh im. A.N. Bakuleva Minzdrava Rossii;2023. (In Russian)

2. Abdominal adhesions: preventive and curative measures. Filenko B.P., Zemlyanoy V.P., Borsak I.I., Ivanov A.S. Saint-Petersburg. 2013. (In Russian)

3. Cannata A., Petrella D., Russo C. F., Bruschi G., Fratto P., Gambacorta M., L. Martinelli. Postsurgical Intrapericardial Adhesions: Mechanisms of Formation and Prevention. Ann Thorac Surg. 2013;95(5):1818-26. doi: 10.1016/j.athoracsur.2012.11.020.

4. Kudryavtseva Ju.A., Nasonova M.V., Zhuravleva I. Ju. Postsurgical adhesion formation in cardiac surgery: problems and perspectives. Patologiya krovoobrashcheniya i kardiokhirurgiya. 2011; 1:100-104 (In Russian)

5. Bokeriya L.A., Sivtsev V.S. Factors, pathogenesis and preventive methods. Annaly Khirurgii (Russian Journal of Surgery). 2014; 19 (6): 7–15 (In Russian)

6. Shurygin M.G., Shurygina I.A. / Prospects for prevention of adhesion process during cardiac surgical interventions. Acta Biomedica Scientifica. 2021;6(6-2):125-132. doi: 10.29413/ABS.2021-6.6-2.13 (In Russian.)

7. Head W.T., Paladugu N., Kwon J.H., Gerry B., Hill M.A., Brennan E.A., Kavarana M.N., Rajab T.K. Adhesion barriers in cardiac surgery: A systematic review of efficacy. J Card Surg. 2022;37(1):176-185. doi: 10.1111/jocs.16062

8. Klicova M, Rosendorf J., Erben J., Horakova J. Antiadhesive Nanofibrous Materials for Medicine: Preventing Undesirable Tissue Adhesions ACS Omega.2023:8(23): 20152-20162. doi: 10.1021/acsomega.3c00341

9. Fujita M., Policastro G.M., Burdick A., Lam H.T., Ungerleider J.L., Braden R.L., Huang D., Osborn K.G., Omens J.H., Madani M.M., Christman K.L. Preventing postsurgical cardiac adhesions with a catechol-functionalized oxime hydrogel. Nat Commun. 2021;12(1):3764. doi: 10.1038/ s41467-021-24104-w.

10. Wang X., Xiang L., Peng Y., Dai Z., Hu Y., Pan X., Zhou X., Zhang H., Feng B. Gelatin/Polycaprolactone Electrospun Nanofibrous Membranes: The Effect of Composition and Physicochemical Properties on Postoperative Cardiac Adhesion. Front Bioeng Biotechnol. 2021;9:792893. doi: 10.3389/fbioe.2021.792893..

11. Chung, K.J.; Kim, Y.J.; Kim, T.G.; Lee, J.H.; Kim, Y.-H. Anti-Adhesive Effect of Porous Polylactide Film in Rats. Polymers (Basel). 2021;13(6):849. doi: 10.3390/polym13060849.

12. Biocompatibility testing of natural and synthetic pericardial adhesion barriers. Shishkova D.K., Kudryavtseva Yu.A., Nasonova M. V., Khodyrevskaya Yu.I., Burkov N.N.. Siberian Medical Journal (Tomsk). 2017. 32(1):111-115. (In Russian)

13. Kudryavczeva Yu.A., Kanony`kina A.Yu., Barbarash L.S. Sposob izgotovleniya protivospaechny`kh polimerny`kh membran s protivovospalitel`ny`mi i antibakterial`ny`mi svojstvami dlya serdechno-sosudistoj i abdominal`noj khirurgii. Patent RU 2823644 C1, 26.07.2024. (In Russian)

14. Chen Z., Zheng J., Zhang J., Li S. A novel bioabsorbable pericardial membrane substitute to reduce postoperative pericardial adhesions in a rabbit model. Interact Cardiovasc Thorac Surg. 2015;21(5):565-72. doi: 10.1093/icvts/ivv213.

15. Hashimoto Y., Yamashita A., Tabuchi M., Zhang Y., Funamoto S., Kishida A. Fibrin Hydrogel Layer-Anchored Pericardial Matrix Prevents Epicardial Adhesion in the Severe Heart Adhesion-Induced Miniature Pig Model. Ann Biomed Eng. 2024;52(2):282-291. doi: 10.1007/s10439-023-03373-0.

16. Stapleton L., Steele A.N., Wang H., Hernandez H.L. Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier. Nature Biomedical Engineering. 2019; 3(8):611-620. doi:10.1038/s41551-019-0442-z

17. Heydorn W.H., Daniel J.S., Wade C.E. A new look at pericardial substitutes. J. Thorac. Cardiovasc. Surg. 1987; 94 (2): 291–6.

18. Rajivт S., Drilling A., Bassiouni A., Harding M, James C., Robinson S., Moratti S., Wormald P.-J. Chitosan Dextran gel as an anti adhesion agent in a postlaminectomy spinal sheep model J Clin Neurosci. 2017.40:153-156. doi: 10.1016/j.jocn.2017.02.010.

19. Maiborodin I.V., Kuznetsova I.V., Beregovoy E.A., Shevela A.I., Barannik M.I., Manaev A.A., Maiborodina V.I. Tissue reactions during the degradation of polylactide implants in the body. Morphology. 2013; 143(3):59-65. (In Russian)

20. Blasi P., D'Souza S.S., Selmin F., DeLuca P.P. Plasticizing effect of water on poly(lactide-co-glycolide). J Control Release. 2005;108(1):1-9. doi: 10.1016/j.jconrel.2005.07.009.