Met Fibrotic tissue formation, a physiological part of wound healing after all surgical interventions, can become a problem when intense ( 1 , 2 ). Undesirable density fibrotic tissue that develops in the epidural space, dura surface, and around the nerve root after laminotomy/laminectomy applied in patients such as narrow spinal canal (NSC), lumbar disc herniation (LDH) who do not benefit from conservative treatment and have surgical indications for Failed Back Surgery (FBS) syndrome ( 3 , 4 ). In order to prevent epidural fibrosis or the resulting fibrosis from reaching the spinal dura mater, it is necessary to create an anatomical or physiological barrier between the dura mater and the m. erector spinae. For this purpose, various biological and non-biological materials have been used for many years. These include fat grafts as solid barriers, fascia grafts, kiel bone grafts, polyvinyl alcohol hydrogel membrane, polytetrafluoroethylene membrane, polylactic acid membrane, vicryl mesh, hyaluronate as the viscous solution, gel as fibrinolytic agent, recombinant plasminogen activator, urokinase gel, hemostat. Sponge, microfibrillar collagen, methylprednisolone, triamcinolone, prednisolone, ketoprofen as an anti-inflammatory agent, dexamethasone, CO ₂ laser, and Antiadhesion Barrier Gel (ADCON-L), a carbohydrate polymer developed in recent years for the prevention of epidural fibrosis, were used ( 5 – 10 ). However, there is no adopted standard treatment protocol to prevent or minimize occurrence of epidural fibrosis ( 11 – 13 ). It is well known that ADCON-L, a carbohydrate polymer developed in recent years, is highly effective in preventing epidural fibrosis, and this is proportional to clinical improvement ( 14 ). Frederickson showed in vitro that astrocytes respond to damage by forming a gliotic scar, that this gliotic scar creates a barrier against the spread of neuritis in the brain, and that proteoglycans, a component of this scar, can inhibit the spread of neuritis ( 15 ). Studies with proteoglycans and related molecules have shown that this substance can act as a barrier against fibroblasts; this formed the scientific logic in the production of ADCON-L ( 16 , 17 ). It has been reported that with further tests on the proteoglycan molecule, it has been determined that the main responsible for the barrier effect is the carbohydrate content, and ADCON-L was developed with this basic logic ( 15 , 18 ).

This study aims to compare the efficacy of ADCON-L and free fat graft used to prevent epidural fibrosis in experimental laminectomy model in rabbits.

This study was carried out within the facilities of Erciyes University Faculty of Medicine (E.U.T.F) Hakan Çetinsaya Experimental and Clinical Research, Orthopedics and Traumatology and Pathology departments.

Ethics Committee approval was obtained from the Erciyes University, Faculty of Medicine, the experimental research ethics Committee (Approval No: 02.02.43, 2003). Our study used 30 adults (1-year-old) male New Zealand-type white rabbits weighing 2500-3000 grams. Three groups of ten were formed. New subjects and all subjects who replaced subjects who died during the study and follow-up period were sacrificed at the end of the 12th week.

Group I (n: 10) control group: The group that underwent laminectomy but no material was placed in the distance.

Group II (n:10) free fat graft group: The autologous free fat graft was placed in the distance after laminectomy.

Group III (n:10) ADCON-L group: The group injected with ADCON-L gel into the (Gliatech, Cleveland, OH,USA) laminectomy distance after laminectomy.

The subjects were taken into operation after fasting for 4 hours. Anesthesia was provided to the subjects by intramuscular injection of 40 mg/kg ketamine hydrochloride (Ketalar 50 mg/ml, 10ml vial, Eczacıbaşı İlaç Sanayi Istanbul, Turkey). Cefazolin sodium (Cefazol I.M. vial 1000 mg, Mustafa Nevzat) at 70 mg/kg was administered intramuscularly for prophylactic purposes. The lumbar region was shaved, and the hair was removed. Subjects were fixed in the prone position on the operating table prepared for this study. After determining the distance in the lumbar region for the operation area, a skin incision of approximately 4 cm was made over the spinous processes from the midline. The iliac wings were palpated, and the L ₅ level was determined. The lumbar fascia was opened from the midline, and the paravertebral muscles were stripped bilaterally by blunt dissection. After the spinous process was removed with a rongeur, a total laminectomy was performed at the L5 level with the help of a drill.

Bleeding was stopped by applying a compress and using Surgicell. Surgicell was removed after bleeding control. After the operation area was washed with physiological saline, the necrotic paravertebral muscles were deprived. No other action was taken in the operation area of Group I. Autologous free fat graft was placed in the laminectomy distance of Group II, covering the dura mater. The free fat graft was obtained by releasing the adipose tissue in the epidural space. 0.5cc of ADCON-L was injected into the laminectomy distance of Group III ( 19 ).

Subjects were sacrificed at week 12. After the skin was opened in all subjects, the prevertebral region was reached with a transverse incision approximately 2 cm distal to and 2 cm proximal to the L5 level. The vertebral column, which was cut with bone scissors, was removed as a whole and sliced at 5mm intervals. It was detected in 10% formaldehyde solution in the Department of Pathology for 48-72 hours. After fixation, they were decalcified in 10% EDTA solution. After decalcification, laminectomy zones were taken into routine tissue follow-up for histopathological examination. After decalcification, laminectomy zones were taken into routine tissue follow-up for histopathological exam. Sections of 3-4 micron thickness were obtained from the blocked tissues with a microtome and stained with Hematoxylin-Eosin (H&E) and Masson Trichrome (MT). The criteria of He et al. ( 20 ) were used in the histopathological evaluation of the obtained preparations by light microscopy (Table 1).

In spinal surgery, epidural fibrosis, which develops on the dural sac and around the nerve root, especially after decompression and LDH surgeries, causes neurological symptoms with the effect of traction or compression, causes the patient's complaints to persist, and/or causes additional complaints, is one of the problems that still awaits a solution in spinal surgery. Research on the causes, prevention, and treatment of epidural fibrosis is ongoing, and opinions differ. Epidural fibrosis is one of the causes accepted to cause FBS syndrome, and it is reported to cause clinical complaints at a rate of 6-25% ( 4 , 21 , 22 ).

Histological examinations in experimental studies showed that after lumbar laminectomy and discectomy, a large hematoma appeared in the first two days, and fibrosis began in 2 weeks and became evident in 4 weeks ( 23 , 24 ). In a study, he et al. examined rats by sacrificing them on the 8 ^th , 15 , 30 , and 90 days ( 20 ). They reported that the laminectomy membrane started to appear on the 15 ^th day, the laminectomy site was closed after 30 days, and after 90 days, massive scar tissue was located on the defect and adhered to the dura mater ( 20 ). Songer et al. reported that the adhesion maturity or strength was not different at the 12 ^th and 26 ^th weeks in their examination in dogs at the 2 ^nd , 4 ^th , 12 ^th , and 26 ^th weeks ( 8 ). Our study aimed to see the final state of scar tissue formation by sacrificing all subjects at the end of the 12 ^th week.

Gerszten et al. found in their study on dogs that the laminectomy defect was covered with scar tissue originating from the paraspinal muscles and advancing toward the epidural region ( 25 ). Yang et al. ( 26 ) and Sobti et al. ( 27 ) found similar results in similar studies. Our study found that fibroblastic proliferation was more in the parts close to the paraspinal muscles. This finding can be interpreted as a substance that will be placed in the laminectomy or laminectomy area and will prevent the progression of the scar and may block the laminectomy membrane. When groups were evaluated regarding fibroblastic proliferation, there was no significant difference between the control and fat graft groups. In contrast, the ADCON-L group's fibroblastic proliferation was considerably lower than the other two groups. La Rocca et al., in their study on dogs, found that the laminectomy defect was covered with scar tissue originating from the paraspinal muscles and advancing toward the epidural region. ( 28 ). Keller et al. and Vaquero et al. found similar results in similar studies. ( 29 , 30 ). Our study found that fibroblastic proliferation was more in the parts close to the paraspinal muscles. This finding can be interpreted as a substance that will be placed in the laminectomy or laminectomy area and will prevent the progression of the scar and may block the laminectomy membrane. When the groups were evaluated regarding fibroblastic proliferation, there was no significant difference between the control and fat graft groups. In contrast, the ADCON-L group's fibroblastic proliferation was considerably lower than the other two groups.

The primary building material of epidural fibrosis or scar tissue is collagen. Fibroblasts form collagen synthesis during wound healing. Barbera et al. determined that the main component originating from the dorsal spinal muscles and filling the laminectomy defect is collagen, and its amount is directly proportional to the size of the scar tissue ( 6 ). Massie et al. determined that main component originating from the dorsal spinal muscles and filling the laminectomy defect is collagen, and its amount is directly proportional to the size of the scar tissue ( 31 ). Ding et al. reached the same conclusion in a similar study ( 32 ). Our study observed that the amount of collagen in the scar tissue showed parallelism with fibroblastic activity in the control and ADCON-L groups but not in the fat graft group.

Autogenous fat grafts are the most effective substance in preventing epidural scarring among the substances ( 33 , 34 ). Vediappan et al. showed in their study that even if the fat graft is alive, it does not prevent the formation of fibrosis in the anterior/antero-lateral regions of the nerve root emerging from the spinal cord ( 35 ). In many cases, the spinal cord was compressed posteriorly by the fat graft. The fat graft may compress the dura posteriorly. In our study, we found moderate scar formation and, in parallel, moderate perineural adhesions in the subjects who used fat grafts. The results were significant compared to the control.

It is known that ADCON-L, a carbohydrate polymer developed in recent years, is highly effective in preventing epidural fibrosis, and this is proportional to clinical improvement ( 11 , 36 ). Kazanci et al. applied ADCON-L to rats after laminectomy and evaluated the scar gross anatomically by microdissection, sacrificing eight weeks later. They reported that ADCON- L reduced epidural fibrosis compared to the control group ( 37 ). Our results were statistically significant, and no adhesion was observed in any subjects using ADCON-L. Dermirel et al. applied ADCON-L to rats after laminectomy, sacrificed the subjects after 2, 4, 8, 16 and 26 weeks, and investigated the effect of ADCON-L gross anatomically and histologically ( 11 ). The surgical area contains minimal scarring, and the dura can be easily seen; In the histological study reported that ADCON-L was resorbed in the fourth week, and there was minimal or no foreign body and inflammatory response to ADCON-L. Kasimcan et al. also reported that the absorption period of ADCON-L was four weeks ( 38 ). In our study results, no foreign body reaction or inflammatory response was observed in any of the subjects using ADCON- L, no residual ADCON-L was found, and it was thought to be completely resorbed. In order to prevent epidural fibrosis, the substance to be used must be resorbed over time because the substance placed for a long time increases the risk of infection.

Epidural fibrosis, a physiological consequence of wound healing after laminectomies, occurred in varying degrees except in ADCON-L injected subjects. We concluded that free autogenous fat grafting does not prevent epidural fibrosis formation at an acceptable level. We concluded that ADCON-L would not cause FBS syndrome because there are no side effects associated with its use, it is absorbed over time, it is easy to apply, the risk of infection is low, and it is an effective substance in the prevention of epidural fibrosis and the second operation can be performed more comfortably and safely in patients who need it. Due to the limited number of studies in the literature, our study makes an essential contribution to the literature. Since the relationship between epidural fibrosis and findings has not been fully demonstrated, we think comparative clinical studies should support the efficacy of ADCON-L.