Postoperative Epidural Fibrosis Research Articles

Postoperative Epidural Fibrosis: Challenges and Opportunities - A Review.

Postoperative epidural fibrosis (EF) is still a major limitation to the success of spine surgery. Fibrotic adhesions in the epidural space, initiated via local trauma and inflammation, can induce difficult-to-treat pain and constitute the main cause of failed back surgery syndrome, which not uncommonly requires operative revision. Manifold agents and methods have been tested for EF relief in order to mitigate this longstanding health burden and its socioeconomic consequences. Although several promising strategies could be identified, few have thus far overcome the high translational hurdle, and there has been little change in standard clinical practice. Nonetheless, notable research progress in the field has put new exciting avenues on the horizon. In this review, we outline the etiology and pathogenesis of EF, portray its clinical and surgical presentation, and critically appraise current efforts and novel approaches toward enhanced prevention and treatment.

Ligamentum Flavum Flap Technique in Lumbar Microdiscectomy.

Microdiscectomy has been the gold-standard technique for the treatment of lumbar disc herniation. A potential reason for suboptimal symptom resolution following microdiscectomy is postoperative epidural fibrosis1. Preservation of the ligamentum flavum through the use of the ligamentum flavum flap technique reduces postoperative epidural fibrosis and leads to a favorable long-term prognosis. The L5-S1 interlaminar space on the operative side is exposed with use of a standard microsurgical approach, and the level is confirmed. The ligamentum flavum is held taut with use of tooth forceps, holding onto superficial layers, and a flap with its base on the lateral side is created. Initial separation is made at the midline (where the flavum is very thin) with use of a no.-15-blade scalpel. The flap is elevated by detaching the ligamentum flavum between the lower border of the L5 lamina and sacrum with use of a 1-mm Kerrison rongeur. The detachment of the ligamentum flavum is performed carefully, preserving the attachments on the lateral border. Having a thin base allows the flap to be elevated and rotated, and the flap thus can be tucked into the muscle above the facet joint. The nerve root is retracted, and discectomy is performed according to the location and size of the disc. After achieving good hemostasis, the ligamentum flavum flap is gently rotated back to its normal position. In most cases, the flap can be returned back to its original position without any gap and without any need for suture. Closure is performed in layers. Nonoperative treatment yields good pain relief in more than 80% of patients with disc herniation. However, if surgery is required, the primary concern for the surgeon is the prevention of postoperative scarring and fibrosis around the nerve root. Previous attempts to mitigate this potential complication have revolved around the placement of a subcutaneous fat graft over the nerve root; however, no firm evidence exists to support this technique. Synthetic materials such as expanded polytetrafluoroethylene, Adcon-L gel (Wright Medical Technologies), and sodium hyaluronate have also been utilized to prevent epidural scarring; however, the ligamentum flavum is a natural biological solution. Postoperative fibrosis may occur if there is a dead space as a result of the excision of the ligamentum flavum or due to inflammation. Restoration of native tissue anatomy with use of the ligamentum flavum technique can prevent such fibrosis, as has been reported previously. In addition to reducing scar formation, preserving the ligamentum flavum can make revision surgery (which is rarely required) safer, as there is less or no epidural fibrosis or nerve root scarring. Patients undergoing this procedure have shown good improvement in the Oswestry Disability Index (ODI) and a clinically notable reduction in visual analog scale (VAS) pain scores in the immediate postoperative period as well as on long-term follow-up. The chances of epidural fibrosis have been shown to be significantly decreased over long-term follow-up. Li et al. reported substantially lower VAS and ODI scores among patients who underwent the ligamentum flavum flap technique compared with a control group, as well as a significantly lower grade of epidural fibrosis at 6 months postoperatively2. In a similar study, Özay et al. highlighted significant clinical improvement and reduced chances of postoperative epidural fibrosis in 51 patients who underwent the ligamentum flavum flap technique3. Additionally, Li et al. showed that patient age and the area of the laminar space were the 2 important factors that determine the preservation of the ligamentum flavum, as the failure rate was significantly higher in elderly patients (>43.5 years) and those with small interlaminar space (<1.95 cm2). ODI and VAS scores were substantially better, and fibrosis formation, as assessed on computed tomography (CT) scans with intravenous iopamidol injection, was significantly reduced in patients with preserved ligamentum flavum4. Properly set up the operating microscope and fluoroscopy unit in order to ensure accurate starting points.Utilize minimal cautery at all levels of dissection.Hold the ligamentum flavum taut superficially while incising with use of a no.-15 scalpel.Detach the ligamentum flavum while safely preserving the attachments on the lateral border.Perform proper repositioning of the ligamentum flavum after achieving hemostasis. ODI = Oswestry Disability IndexVAS = visual analog scaleCT = computed tomographyLF = ligamentum flapSLRT = straight leg raise testAP = anteroposteriorMRI = magnetic resonance imagingASIS = anterior superior iliac spineCSF = cerebrospinal fluid.

Comparison of the effectiveness of diclofenac sodium and tenoxicam in the prevention of epidural fibrosis by topical application with an absorbable gelatin sponge on the dura in an experimental laminectomy model.

There has been an increasing trend in spinal surgery interventions in recent years. Low back pain is a disorder that is seen at least once in the lifetime of approximately 80% of the general population. Today, neurosurgeons perform operations including laminectomy for various reasons. Epidural fibrosis is a scar tissue that develops after posterior spinal surgery. Various synthetic and organic materials have been used in experimental studies to prevent epidural fibrosis in laminectomy defects. In this study we aimed to investigate and observe histopathologically the effectiveness of cyclooxygenase inhibitor drugs; tenoxicam and diclofenac sodium in the experimental rat laminectomy model in preventing the postoperative spinal epidural fibrosis. In this study, 32 Wistar-Albino female rats were used. 8 mg/kg tenoxicam and 1.5 mg/kg diclofenac sodium were applied on the dura with an absorbable gelatin sponge. After decapitation, L1-L4 laminectomy area was totally removed and histopathological examination was performed. It has been shown that the topical application of diclofenac sodium and tenoxicam, which are selective Cox inhibitor drugs, prevents fibroblast migration by forming a local barrier and Cox inhibitors are caused by the inhibition of prostanoids, which are inflammatory mediators.

High-Frequency Bipolar Coagulation Limits Epidural Fibrosis in Lumbar Microdiscectomy.

We propose a vast study to examine the effect of high-frequency bipolar coagulation used in the operating room to prevent the development of epidural fibrosis after lumbar microdiscectomy. A total of 1004 participants were divided into two groups: no high-frequency bipolar coagulation (NC group) and high-frequency bipolar coagulation (C group). Postoperative epidural fibrosis, infection rates, reoperation status, and dural injury complications during the operation were recorded. Considering the epidural fibrosis rates of the two groups, epidural fibrosis was seen in 10.6% of the patients in the NC group. In contrast, it was seen in only 6.2% of the patients in the C group. The complication of epidural fibrosis that develops after lumbar microsurgery operations both impairs patient comfort and brings with it the complications of reoperation. After performing hemostasis with bipolar, coagulating the annulus may effectively reduce epidural fibrosis and prevent reoperation.

Artificial lamina after laminectomy: Progress, applications, and future perspectives.

In clinical practice, laminectomy is a commonly used procedure for spinal decompression in patients suffering from spinal disorders such as ossification of ligamentum flavum, lumbar stenosis, severe spinal fracture, and intraspinal tumors. However, the loss of posterior column bony support, the extensive proliferation of fibroblasts and scar formation after laminectomy, and other complications (such as postoperative epidural fibrosis and iatrogenic instability) may cause new symptoms requiring revision surgery. Implantation of an artificial lamina prosthesis is one of the most important methods to avoid post-laminectomy complications. Artificial lamina is a type of synthetic lamina tissue made of various materials and shapes designed to replace the resected autologous lamina. Artificial laminae can provide a barrier between the dural sac and posterior soft tissues to prevent postoperative epidural fibrosis and paravertebral muscle compression and provide mechanical support to maintain spinal alignment. In this paper, we briefly review the complications of laminectomy and the necessity of artificial lamina, then we review various artificial laminae from clinical practice and laboratory research perspectives. Based on a combination of additive manufacturing technology and finite element analysis for spine surgery, we propose a new designing perspective of artificial lamina for potential use in clinical practice.

Long-term outcomes of the repeated lumbar microdiscectomies using polyacrylamide hydrogel: clinico-radiological relevance

Background. Epidural fibrosis (EF) is one of the reasons of the failed back surgery syndrome manifesting in back pain and pain in extremities as well as other signs of the compression or irritation of the nerve structures. The numerous approaches to prevent EF have been elaborated. Nowadays, many years of experience in the usage of different barrier materials in microdiscectomy such as polyacrylamide hydrogel (PAH) have been accumulated. Nevertheless, the results of such treatment are rather controversial. The aim of the study was to assess the radiological data on the state of the backbone according to MRI findings and the clinical symptoms of the patients following the surgery as well as to determine the long-term strength of the interaction between the factors under study after the repeated lumbar microdiscectomies performed with intraoperative epidural PAH administration. Materials and methods. The results of the clinical and radiological assessment of 96 patients (mean age 45.7 years; 95 % CI [43.5; 47.9]; 59 males and 37 females) enrolled into the single-center prospective cohort study performed at the State Institution «Romodanov Neurosurgery Institute National Academy of Medical Sciences of Ukraine» have been presented. The patients were divided into two groups. The main group (MG) consisted of 35 (36.5 %) patients with recurrent intervertebtral disc (IVD) herniation to whom PAH was administered epidurally at the final step of the surgery comprising disc removal and decompression of the nervous structures with the aim of preventing cicatrical adhesive EF. In control group (61 patients, 63.5 %), barrier materials were not used. The primary end-points of the study were the long-term outcomes of the repeated lumbar microdiscectomies: EF rate at the postoperative site; the rate of the displacement of spinal root at the postoperative site; the rate of the repeated recurrent IVD herniation and de novo IVD herniation; the rate of the cases with the residual radicular pain localized in the area of the surgical intervention and the extent of the worsening of life quality in the treated patients. The secondary end-points of the study were the following: the analysis of the associations with delineation of the strength of such factorsaffecting the residual radicular pain as EF, the displacement of spinal root at the postoperative site, the repeated recurrent IVD herniation the repeated recurrent IVD herniation and de novo IVD herniation. Results. In 12 months following the surgical treatment, EF frequency was significantly lower in MG as compared with CG where PAH was not used (p = 0.02936). Nevertheless, the difference between groups was not significant when MRI findings of the displacement of spinal root at the postoperative site (р = 0.46759), the frequency of the repeated recurrent IVD herniation (p = 0.90904) and de novo IVD herniation (p = 0.60385) were compared. In study group, there were no association between MRI signs of postoperative EF, the displacement of spinal root or new recurrent IVD herniation on the one hand and the frequency of the radicular pain localized at the area of the surgical intervention on the other hand (p = 0.66482; p = 0.09515; p = 0.22857, respectively). In CG, the significant association between the displacement of spinal root at the postoperative site and the clinical symptoms above was revealed (p = 0.00222) with association coefficient φ = 0.41 indicating the moderate strength of this association. Conclusions. The data obtained generally suggest the reasonability of applying PAH manufactured in Ukraine as a barrier material at least for the treatment of the patients with recurrent IVD herniation representing the challenging category of spinal patients.

The Preventive Effect of Decorin on Epidural Fibrosis and Epidural Adhesions After Laminectomy.

Laminectomy is commonly performed to treat degenerative spinal diseases by reducing compression on the spinal cord and nerve roots. The postoperative epidural fibrosis and epidural adhesions may result in failed back surgery syndrome, which is characterized by the symptoms of lower back pain or leg pain. There is currently no satisfactory treatment for this complication. The pathological processes of epidural fibrosis and epidural adhesions are relevant to the proliferation of fibroblasts, transdifferentiation of fibroblasts into myofibroblasts, and the excessive deposition of extracellular matrix (ECM) protein. According to reports, transforming growth factor-β1 (TGF-β1) played a vital role in the development of fibrosis by promoting aforementioned processes. Decorin, an endogenous proteoglycan and natural inhibitor of TGF-β1, has exhibited prominent anti-fibrosis activity in various scar formation and fibrosis models of many organs. However, the preventive effect of decorin on epidural fibrosis and epidural adhesions requires further investigation. Here, we investigated the therapeutic effects and potential mechanisms of decorin on epidural fibrosis and epidural adhesions. Our results indicated that decorin could significantly suppress the TGF-β1-induced proliferation, transdifferentiation, and extracellular matrix production in primary fibroblasts. Furthermore, Smad2/3 signaling pathway had been demonstrated to be involved in the preventive effect of decorin. Moreover, administration of decorin in vivo could notably inhibit epidural fibrosis and epidural adhesions after laminectomy. To date, there is no approved therapy to target TGF-β1 for the treatment of epidural fibrosis and epidural adhesions after laminectomy. Our research proved the anti-fibrosis effect of decorin, which may provide an effective and promising treatment for epidural fibrosis and epidural adhesions.

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&lt;0.001), the number of fibroblasts (F = 11.158, p&lt;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.

IFN-α-2b Inhibits the Proliferation and Migration of Fibroblasts via the TGFβ/Smad Signaling Pathway to Reduce Postoperative Epidural Fibrosis

Epidural fibrosis after lumbar laminectomy refers to a serious complication, and excessive proliferation of fibroblasts is considered the major factor. Interferon-alpha-2b (IFN-α-2b) can exert antiviral and antiproliferative effects, which has been suggested to effectively prevent several fibrotic diseases. However, the effect of IFN-α-2b on the prevention of epidural fibrosis (EF) and its possible mechanism remain unclear. In this study, in vitro and in vivo experiments were performed to examine the possible mechanism of IFN-α-2b for preventing EF. Cell counting kit-8 (CCK-8), cell cycle test, Edu incorporation, wound healing assay, transwell test, and Western blotting assay were performed to investigate the inhibitory effect of IFN-α-2b on the proliferation and migration of fibroblasts in vitro. As indicated from the results, IFN-α-2b was capable of inhibiting proliferation and migration of fibroblasts and inhibiting the activity of the transforming growth factor β (TGFβ)/Smad signaling pathway. In vivo, the effect of IFN-α-2b on the reduction of EF was determined by performing histological macroscopic evaluation and histological and immunohistochemical staining. As suggested from the results, IFN-α-2b significantly inhibited EF after laminectomy. As revealed from the mentioned results, IFN-α-2b may have a promising application for preventing EF in the future.

Antifibrotic Effect of Bletilla striata Polysaccharide-Resveratrol-Impregnated Dual-Layer Carboxymethyl Cellulose-Based Sponge for The Prevention of Epidural Fibrosis after Laminectomy.

The application of antifibrotic materials can alleviate epidural fibrosis by restricting excessive fibroblast proliferation and mitigating scar tissue formation. Here, a biodegradable carboxymethyl cellulose (CMC)-Bletilla striata polysaccharide (BSP)-resveratrol (RES) sponge was fabricated to inhibit scar tissue formation post laminectomy surgery. Fibroblasts NIH/3T3, myoblasts C2C12, neural cells PC-12, and Schwann cells RSC96 were used to evaluate the in vitro cytocompatibility. Laminectomies on 10 Sprague–Dawley rats with/without the application of the CMC-BSP-RES sponge were performed. The severity of adhesion between the dura mater and formed scar tissue was qualitatively scored. All cell lines exhibited good viability with no significant difference in cytotoxicity when cultured with variable extractions of the CMC-BSP-RES sponge. S100a4 and P4hb expressions were downregulated in NIH/3T3 cultured in the CMC-BSP-RES sponge, implying that this sponge potentially inhibits fibroblast activity. No post-operative shrinkage or dura mater expansion along the surgical site was detected. The peel-off tests revealed that the tenacity of adhesion de-creased. Histopathological examinations verified that the average number of fibroblasts in the CMC-BSP-RES group considerably decreased. The CMC-BSP-RES sponge is a biocompatible and effective material for alleviating post-operative epidural fibrosis and mitigating fibroblast expression following laminectomy.

Microsphere-Embedded Hydrogel Sustained-Release System to Inhibit Postoperative Epidural Fibrosis.

As a common complication of spine surgery, postoperative epidural fibrosis is an important cause of failed back surgery syndrome (FBSS), yet there is no effective clinical intervention to tackle it. Herein, for the first time, we develop a strategy of combining a gelatin methacryloyl (GelMA) hydrogel matrix with poly(lactic-co-glycolic acid) (PLGA) microsphere-encapsulated resveratrol (RSV), which aims to synergistically promote the inhibition effect on epidural fibrosis. The resultant RSV@PLGA-GelMA (8% w/v) hydrogels possess optimal mechanical properties and prompt the matrix sustainably and stably to release RSV for several weeks. It is further shown that the hybrid hydrogels without the drug exhibit good biosafety without distinct cytotoxicity, while RSV@PLGA-GelMA could prevent fibroblast proliferation and migration. Further rat laminectomy model indicates that the RSV@PLGA-GelMA hydrogels reduce epidural fibrosis by inhibiting fibroblast proliferation and extracellular matrix overexpression and deposition via a TGF-β/Smad signaling pathway. Consequently, we believe that such a creative structural combination will be a promising strategy for preventing postoperative epidural fibrosis of spine surgery.

The use of various materials and drugs for the prevention of the development of postoperative lumbar epidural fibrosis: literature review

The paper is a review of the current literature data on the use of various materials and drugs for the prevention of the development of postoperative lumbar epidural fibrosis. Literature searches were performed in the Pubmed, Medline, EMBASE, Cochrane Library and eLibrary databases. The formation and growth of fibrous tissue in the epidural space, followed by tissue adhesion to the dura mater, is the leading cause of pain afferentation in the lumbar spine and/or lower extremities. Several molecular and cellular mechanisms play an important role in the pathophysiology of connective tissue formation in the epidural space. An analysis of experimental and clinical studies examining the effectiveness of various materials and drugs is presented. The authors present the current data on new therapeutic approaches to the prevention of postoperative epidural fibrosis. Topical, unresolved issues which necessitate further research on the pathophysiology of epidural fibrosis are indicated.

Postoperative Epidural Fibrosis Prevention: Which Is Better-Autologous Fat versus Gelfoam.

Study DesignProspective, randomized study of 100 patients with prolapsed intervertebral disc with an average of 12- to 18-month follow-up postoperatively.PurposeTo compare the role of Gelfoam and autologous fat in the prevention of postoperative epidural fibrosis (EF) after lumbar spine surgery.Overview of LiteratureEF is a possible sequelae of lumbar disc surgery. Different treatments and surgical strategies have been attempted to prevent postoperative fibrosis without providing consistent long-term results.MethodsThe study was conducted on 100 adult patients. The patients were randomly allocated into two groups of 50 patients each: group A, autologous fat group, and group B, Gelfoam group. The postoperative follow-up was conducted at intervals of 6 weeks, 3 months, 6 months, and 12 months. Both groups were evaluated clinically (Oswestry Low Back Pain Disability Questionnaire [ODI], Visual Analog Scale [VAS], Straight Leg Raising Test [SLRT]) and radiologically (using Ross grading by contrast magnetic resonance imaging [MRI]) for development of radicular pain and hence EF.ResultsBased on the analysis, improvement in mean values of ODI score, VAS score, and SLRT were found to be statistically significant postoperatively at intervals of 6 weeks, 3 months, 6 months, and 12 months when compared individually in both groups. However, improvement was greater in the autologous fat group than in the Gelfoam group. Based on contrast-enhanced MRI, the number of patients who developed EF was smaller in the autologous fat group than in the Gelfoam group.ConclusionsIn the present study, on clinical and radiological assessment, we conclude that both groups prevent radicular pain and postoperative EF individually but relatively autologous fat was found to be more effective than Gelfoam in the prevention of EF and hence radicular pain.

Dose preservation of ligament flavum really help prevent postoperative epidural fibrosis and improve outcome in microdiscectomy?

ObjectiveA prospective, randomized, controlled clinical study was conducted with surgery performed by the same surgeon. The aim was to present a new technique for preserving the ligament flavum during lumbar microdiscectomy, and to evaluate whether this helps prevent postoperative fibrosis and improve outcome. MethodsFrom January to December 2017, 251 patients with indication for microdiscectomy were randomly divided into test group using ligament flavum preservation technique and control group using conventional procedures. Visual analogue scale (VAS) scores and Oswestry Disability Index (ODI) were assessed before the surgery, and 3 days, 1 month, 6 months, 1 year and 2 years after the operation respectively. The grade of epidural fibrosis on MRI after 6 months was evaluated by two radiologists independently and double-blindly. ResultsBoth groups’ VAS and ODI were significantly improved after surgery, but there was no significant difference between two groups at 3d and 1 month after operation. The grade of epidural fibrosis in test group was significantly lower than that in control group at 6 months postoperative. The VAS and ODI were significantly lower in test group than that in control group at 6 months,1 year and 2 years after operation. ConclusionPreservation of more ligament flavum is practicable during the procedure of microdiscectomy. It can prevent postoperative epidural fibrosis, and is helpful to achieve a better clinical outcome.

A comparative study between laminectomy and laminotomy in patient of lumbar disc prolapse

Introduction and Objective: The study aims to compare the effectiveness of laminectomy and laminotomy for treating lumbar disc prolapse. Materials and Methods: A prospective study of comparative study between laminectomy and laminotomy. In patient of lumbar disc bulge will be conducted in the department of Orhtopaedics, Sir Takhtsinhji Hospital, Bhavnagar, after getting permission from Institutional Review Board, Government Medical College, Bhavnagar. The Study will compose of 30 patients of lumbar disc bulge admitted in the Department of Orhtopaedics, Sir Takhtsinhji General Hospital, Bhavnagar. Patients will be included after approval of Institutional Review Board, Government Medical College, Bhavnagar. Detailed history regarding personal date, history of mechanism, pre- injury ambulatory status, preexisting local and systemic condition, menopausal status that may affect recovery. Full clinical examination will be done to assess the general condition of the patient, range of movement and any associated complains. MRI whole spine screening will be taken. After deciding the appropriate plan, patient will be prepared for surgery. Every patient will be operated upon as early as possible or within two days of getting fitness for anesthesia. All patients will be assessed with regard to operative time day of getting fitness for anesthesia. All patients will be assessed with regard to operative time, blood loose, hospital stay and post operative complications. Dressing will be checked on the 2nd , 4th, 6th post – operative day. Patients will be discharged and then after will be followed on 2nd wk, 6th wk, 12th wk, and 6th month. On follow up visits patients’ will be evaluated with odoms criteria, general and systemic examination. Results: Laminotomy has definitive advantages over leminectomy in terms of SHORT hospital stay an average of 5 days, less blood loss, Less postoperative pain and Epidural hematomas and Fibrosis, It has the advantage that it’s shorter length

Emodin promotes fibroblast apoptosis and prevents epidural fibrosis through PERK pathway in rats

BackgroundLaminectomy is usually classed as a common orthopedic surgery, but postoperative epidural fibrosis often leads to less-than-desirable clinical outcomes. As demonstrated by prior studies, emodin (EMO) exerts an anti-fibrotic effect. Here, we carried out investigation into the inhibitory effect created by EMO application on epidural fibrosis after laminectomy in rats.MethodsThe paper conducts a series of experiment. In vitro, we observed the effect of EMO on fibroblasts by Cell Counting Kit-8 (CCK-8) assay. Apoptosis of fibroblasts induced by EMO was detected by western blot, TUNEL assay, and flow cytometry. The results revealed that EMO was capable of inducing fibroblast apoptosis, and the proteins of PERK pathway also changed accordingly. In vivo, the effect of EMO on epidural fibrosis in 12 male Sprague-Dawley rats was observed by histological staining.ResultsCCK-8 assay indicated that EMO was effective in reducing fibroblast viability in a time- and a dose-dependent manner. TUNEL assay and flow cytometry analysis have demonstrated that the apoptotic rate of fibroblasts increased as the EMO concentration rose. Western blot analysis proved that EMO promoted the relative expression of p-perk and p-eIF2α and that the expression of its downstream proteins CHOP and GRP78 was also enhanced. The expression of apoptotic protein Bax and cleaved PARP was upregulated, whereas the expression of anti-apoptotic protein Bcl-2 was downregulated. In addition, histological and immunohistochemical analysis demonstrated that EMO functioned to inhibit epidural fibrosis and increase GRP78 expression in fibrous tissue by promoting apoptosis of fibroblasts.ConclusionsEMO could have inhibitory effect on epidural fibrosis in a concentration-dependent manner. The potential mechanism might be through PERK signaling pathway to promote fibroblast apoptosis. It has a possibility to be taken as a novel method for the treatment of epidural fibrosis.

Prevention of postoperative epidural fibrosis: current status of the issue

Epidural fibrosis is a common cause of a failed back surgery syndrome. The current scientific literature proposed many methods for prevention of epidural fibrosis, however, universal methods to fully solve the problem was not found. Prevention tasks in the preoperative period include the identification of risk factors for the development of epidural fibrosis with the correction of the revealed violations. Intraoperative prevention involves the development of barriers in the form of natural and synthetic polymeric materials that impede the formation of epidural fibrosis after laminectomy. The complex of measures to prevent the development of epidural fibrosis in the postoperative period is supposed to include a list of manipulations consisting of epidural blockades with a common complex anti-inflammatory drug therapy. The study presents an analysis of 63 literary sources from PubMed, EMBASE, Cochrane Library, and eLIBRARY databases most fully reflecting the pathogenetically substantiated prevention of the epidural fibrosis development in the preoperative, intraoperative and postoperative periods.

A novel bacterial cellulose membrane immobilized with human umbilical cord mesenchymal stem cells-derived exosome prevents epidural fibrosis.

IntroductionFailed back surgery syndrome is a situation where there is failure after lumbar surgery aimed at correcting lumbar disease that is characterized by continuous back and/or leg pain. Epidural fibrosis and adhesions are among the major causes of failed back surgery syndrome. In recent years, several biomaterials have been applied as barriers or deterrents to prevent the compression of neural structures by postsurgical fibrosis.MethodsIn this study, a new bacterial cellulose (BC) anti-adhesion membrane, composed of exosomes from human umbilical cord mesenchymal stem cells, was developed. Its structure and morphology, water content, thickness, and mechanical properties of elasticity were analyzed and characterized. The degradation of the BC+exosomes (BC+Exos) membrane in vitro was evaluated, and its in vitro cytotoxicity and in vivo biocompatibility were tested. The prevention effect of BC+Exos membrane on epidural fibrosis post-laminectomy in a rabbit model was investigated.ResultsThe BC+Exos membrane showed a three-dimensional network structure constituted of high-purity cellulose and moderate mechanical properties. No degeneration was observed. The BC+Exos membrane showed no cytotoxicity and displayed biocompatibility in vivo. The BC+Exos film was able to inhibit epidural fibrosis and peridural adhesions.ConclusionBased on the current findings, the BC+Exos membrane is a promising material to prevent postoperative epidural fibrosis and adhesion.

Revisiting Ligament-Sparing Lumbar Microdiscectomy: When to Preserve Ligamentum Flavum and How to Evaluate Radiological Results for Epidural Fibrosis.

Preserving the ligamentum flavum (LF) during lumbar spine surgery can help to limit the extent of postoperative epidural fibrosis (EF), which is a potential cause of persistent leg pain. We present a retrospective analysis of microdiscectomy with preservation of the LF to evaluate the effects of the two LF mobilizing techniques (reflecting inferiorly or medially vs. removing completely) on EF and clinical outcomes. Microdiscectomy was performed through a unilateral laminotomy in 93 patients (52 male, 41 female; mean age, 46 years; range, 25-65 years) with L3-L4 (n= 3), L4-L5 (n= 40), and L5-S1 (n= 50) lumbar disc herniation. Patients whose LF was removed were assigned to group 1 (n=42), and patients whose LF was preserved by mobilizing it medially (n= 31) or inferiorly (n= 20) were assigned to groups 2 and 3, respectively. Follow-up visual analog scale (VAS) scores and magnetic resonance images were evaluated. EF scores, particularly for the anterior quadrants, were significantly higher in group 1 than in groups 2 (P= 0.012) and 3 (P= 0.001). Likewise, postoperative VAS scores in group 1 were also significantly higher than in groups 2 (P= 0.009) and 3 (P= 0.044). Our results demonstrate that 1) preserving the LF during lumbar microdiscectomy reduces the formation of postoperative EF and improves clinical outcomes; 2) EF in the anterior, rather than the posterior epidural space, is correlated with clinical results; and 3) the ligament mobilizing technique used should be individually tailored on the basis of the features of disc herniation.

A Novel Technique for Cervical Laminoplasty Fusion: Simultaneously Enhancing Stabilization and Decompression in Various Cervical Myelopathies: A Technical Note and Outcomes.

Cervical laminectomy has 2 major disadvantages: postlaminectomy adhesion of dural membrane and lack of a fusion bed. The objective of this study was to determine whether simultaneous cervical laminoplasty with fusion (CLPF) might overcome these unwanted outcomes. Patients who underwent CLPF for treating cervical myelopathy with instability who were followed up for at least 12 months were enrolled. Preoperative and postoperative Neck Disability Index (NDI) and Japanese Orthopedic Association (JOA) scores before and after surgery, recovery rates (RRs), C2-C7 lordosis, and fusion success rates were evaluated. The study cohort comprised 50 patients (35males and 15 females; mean age, 60.5 ± 14.0 years) who underwent CLPF. The average duration of clinical follow-up was 24.6 ± 16.1 months. Mean preoperative and postoperative NDI scores were 27.0 ± 10.6 and 17.6 ± 7.2, respectively (P= 0.004). Mean preoperative and postoperative JOA scores were 10.4 ± 4.2 and 13.6 ± 3.0, respectively (P= 0.001). The mean JOA RR was 49.8 ± 42.2%. No significant changes in C2-7 lordosis were noted after surgery (preoperative, 7.0 ± 8.0°; postoperative, 7.3 ± 6.3°; P= 0.789). The fusion success rate was 96% (48 of 50 patients). Fusion mass areas at C5 level were significantly different between the opening side and the hinge side (opening side, 15.8 ± 13.1 mm2; hinge side, 50.8 ± 27.2 mm2; P < 0.001). There was no postoperative restenosis or epidural fibrosis. CLPF might be useful for canal decompression and a good fusion bed while avoiding postoperative epidural fibrosis.