The effectiveness of spatially cross-linked polymer in the postoperative epidural fibrosis prevention: an experimental study

Introduction. Epidural fibrosis is an urgent problem in modern spinal surgery and orthopedics. The formation of connective tissue in the epidural space after performing surgical interventions on the spinal column inevitably leads to adhesion of the latter to the dura mater and compression of neural structures, followed by the formation of clinical and neurological symptoms. The  search for literary sources in domestic and foreign scientific databases has demonstrated the presence of several works studying the effectiveness of barrier methods for preventing the development of epidural fibrosis. It should be noted that the results of these studies are ambiguous and largely contradictory.

The purpose was to study the effectiveness of using a spatially cross-linked polymer in the postoperative lumbar epidural fibrosis prevention in an experiment.

Materials and methods. The study included 26 male Wistar rats (average body weight 338.5±9.07 g), which were divided into two groups: Group I (control, n = 12): animals underwent laminectomy at the level of vertebral bodies LVII – SI  without application of spatially crosslinked polymer; Group II (experimental, n = 14): animals underwent laminectomy at the level of vertebral bodies LVII – SI  followed by application of a spatially cross-linked polymer to the dura mater. The morphological and instrumental parameters were studied.

Results. Significant differences were noted in the severity of epidural fibrosis (χ2 = 14.846, p = 0.003), the number of newly formed vessels (F = 14.371, p<0.001), the number of fibroblasts (F = 11.158, p<0.001), as well as in the severity of vertebral stenosis channe l according to multislice computed tomography (χ2 = 17.207, p=0.002) between the control and experimental groups of animals.

Conclusion. Application of a spatially cross-linked polymer to the dura mater is an effective way to prevent the development of postoperative epidural fibrosis.

1. Samy Abdou M, Hardy RW Jr. Epidural fibrosis and the failed back surgery syndrome: history and physical findings. Neurol Res. 1999; 21 (1): 5–8. doi: 10.1080/01616412.1999.11758603

2. Masopust V, Häckel M, Netuka D, Bradác O, Rokyta R, Vrabec M. Postoperative epidural fibrosis. Clin J Pain. 2009; 25 (7): 600–606. doi: 10.1097/AJP.0b013e3181a5b665

3. Zhivotenko АP, Sorokovikov VA, Koshkareva ZV, Negreeva MB, Potapov VE, Gorbunov AV. Modern concepts of epidural fibrosis (literature review). Acta Biomed Scient. 2017; 2 (6): 27–33. doi: org/10.12737/article_5a0a7f9e412601.50968513 (in Russ)

4. Clancy C, Quinn A, Wilson F. The aetiologies of Failed Back Surgery Syndrome: A systematic review. J Back Musculoskelet Rehabil. 2017; 30 (3): 395–402. doi: 10.3233/BMR-150318

5. Mohi Eldin MM, Abdel Razek NM. Epidural Fibrosis after Lumbar Disc Surgery Prevention and Outcome Evaluation. Asian Spine Journal. 2015; 9 (3): 370–385. doi: 10.4184/asj.2015.9.3.370

6. Baber Z, Erdek MA. Failed back surgery syndrome: current perspectives. J Pain Res. 2016; 7 (9): 979–987. doi: 10.2147/JPR.S92776

7. Liu J, Ni B, Zhu L, Yang J, Cao X, Zhou W. Mitomycin C-polyethylene glycol controlled-release film inhibits collagen secretion and induces apoptosis of fibroblasts in the early wound of a postlaminectomy rat model. Spine J. 2010; 10 (5): 441–447. doi: 10.1016/j.spinee.2010.02.017

8. Amirdelfan K, Webster L, Poree L, Sukul V, McRoberts P. Treatment Options for Failed Back Surgery Syndrome Patients With Refractory Chronic Pain: An Evidence Based Approach. Spine (Phila Pa 1976). 2017; 42 (14): 41–52. doi: 10.1097/BRS.0000000000002217

9. Ozturk Y, Bozkurt I, Yaman ME, et al. Histopathologic Analysis of Tamoxifen on Epidural Fibrosis. World Neurosurg. 2018; 111: e941-e948. doi: 10.1016/j.wneu.2018.01.004

10. Häckel M, Masopust V, Bojar M, Ghaly Y, Horínek D. The epidural steroids in the prevention of epidural fibrosis: MRI and clinical findings. Neuro Endocrinol Lett. 2009; 30 (1): 51–55

11. Percie du Sert N, Ahluwalia A, Alam S, et al. Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol. 2020; 18 (7): e3000411. doi: 10.1371/journal.pbio.3000411

12. Isık S, Taşkapılıoğlu MÖ, Atalay FO, Dogan S. Effects of cross-linked high-molecular-weight hyaluronic acid on epidural fibrosis: experimental study. J Neurosurg Spine. 2015; 22 (1): 94–100. doi: 10.3171/2014.10.SPINE131147

13. Demirel E, Yildiz K, Çadirci K, Aygün H, Şenocak E, Gündoğdu B. Effect of platelet-rich fibrin on epidural fibrosis and comparison to ADCON® Gel and hyaluronic acid. Acta Orthop Traumatol Turc. 2018; 52 (6):469–474. doi: 10.1016/j.aott.2018.07.005

14. Anitua E, Nurden P, Prado R, Nurden AT, Padilla S. Autologous fibrin scaffolds: When platelet- and plasma-derived biomolecules meet fibrin. Biomaterials. 2019; 192: 440–460. doi: 10.1016/j.biomaterials.2018.11.029.

15. Carvalho M, Costa LM, Pereira JE, et al. The role of hybrid chitosan membranes on scarring process following lumbar surgery: post-laminectomy experimental model. Neurol Res. 2015; 37 (1): 23–29. doi: 10.1179/1743132814Y.0000000414

16. Li X, Chen L, Lin H, et al. Efficacy of Poly (D, L–Lactic Acid-co-Glycolic acid) – Poly (Ethylene Glycol) – Poly (D, L–Lactic Acid-co-Glycolic Acid) Thermogel As a Barrier to Prevent Spinal Epidural Fibrosis in a Postlaminectomy Rat Model. Clin Spine Surg. 2017; 30 (3):E283-E290. doi:10.1097/BSD.0000000000000221

17. Lee JY, Stenzel W, Ebel H, Wedekind C, Ernestus RI, Klug N. Mitomycin C in preventing spinal epidural fibrosis in a laminectomy model in rats. J Neurosurg. 2004; 100 (1): 52–55. doi: 10.3171/spi.2004.100.1.0052

18. Wang BB, Xie H, Wu T, et al. Controlled-release mitomycin C-polylactic acid film prevents epidural scar hyperplasia after laminectomy by inducing fibroblast autophagy and regulating the expression of miRNAs. Eur Rev Med Pharmacol Sci. 2017; 21 (10): 2526–2537

19. Numthavaj P, Tanjararak K, Roongpuvapaht B, McEvoy M, Attia J, Thakkinstian A. Efficacy of Mitomycin C for postoperative endoscopic sinus surgery: a systematic review and meta-analysis. Clin Otolaryngol. 2013; 38 (3): 198–207. doi: 10.1111/coa.12114

20. Kasimcan MO, Bakar B, Aktaş S, Alhan A, Yilmaz M. Effectiveness of the biophysical barriers on the peridural fibrosis of a postlaminectomy rat model: an experimental research. Injury. 2011;42 (8):778–781. doi: 10.1016/j.injury.2010.12.017

21. Ismailoglu O, Kizilay Z, Cetin NK, Topcu A, Berber O. Effect of Curcumin on the Formation of Epidural Fibrosis in an Experimental Laminectomy Model in Rats. Turk Neurosurg. 2019; 29 (3): 440–444. doi: 10.5137/1019–5149.JTN.24773-18.1

22. Kizilay Z, Cetin NK, Topcu A, et al. Effect of Etanercept on the Formation of Epidural Fibrosis in an Experimental Model. Turk Neurosurg. 2018; 28 (1): 111–117. doi: 10.5137/1019-5149.JTN.18460-16.1

23. Sun Y, Zhao S, Li X, et al. Local application of rapamycin reduces epidural fibrosis after laminectomy via inhibiting fibroblast proliferation and prompting apoptosis. J Orthop Surg Res. 2016;11 (1): 58. doi: 10.1186/s13018-016-0391-0