Epidural Scar Formation Research Articles

Hydrogen-releasing magnesium hydrogel mitigates post laminectomy epidural fibrosis through inhibition of neutrophil extracellular traps

Epidural fibrosis is a primary contributor to the failure of laminectomy surgeries, leading to the development of failed back surgery syndrome (FBSS). Post-laminectomy, neutrophils infiltrate the surgical site, generating neutrophil extracellular traps (NETs) that contribute to epidural fibrosis. Reactive oxygen species (ROS) play a pivotal role in mediating NETs formation. Molecular hydrogen, recognized for its selective antioxidant properties and biosafety, emerges as a potential therapeutic gas in suppressing epidural fibrosis. In this study, we developed an in-situ hydrogen release hydrogel that inhibits the formation of NETs and mitigates epidural scarring. Biodegradable magnesium (Mg) microspheres served as a hydrogen source, coated with PLGA to regulate hydrogen release. These microspheres (Mg@PLGA) were then incorporated into a PLGA-PEG-PLGA thermosensitive hydrogel (Mg@PLGA@Gel), providing a surgical implant for sustained, long-term hydrogen release. In vitro experiments confirmed the biocompatibility of the system, demonstrating that hydrogen produced by Mg@PLGA effectively neutralizes neutrophil intracellular ROS and inhibits NETs formation. Histological analyses, including H&E staining, MRI, Masson staining, and immunohistochemistry, collectively indicate that Mg@PLGA@Gel is biocompatible and effectively inhibits epidural fibrosis post-laminectomy. Furthermore, Mg@PLGA@Gel inhibits ROS accumulation and NETs formation at the surgical site. These findings suggest that Mg@PLGA@Gel ensures continuous, therapeutic hydrogen concentration, providing relief from epidural fibrosis in a laminectomy mouse model. Statement of significance•The hydrogen-releasing hydrogel combines the therapeutic effects of a physical barrier with immunomodulation.•In situ-generated molecular hydrogen scavenges ROS caused by surgical stress and suppresses NETs formation.•The hydrogen-releasing hydrogel is demonstrated to exhibit high biocompatibility and inhibit epidural scar formation in vivo.

LncRNA-COX2 inhibits Fibroblast Activation and Epidural Fibrosis by Targeting EGR1.

Rationale: Epidural fibrosis is one of the contributors to failed back surgery syndrome (FBSS) with a high incidence of about 80,000 cases per year. The fibrosis spreads from the operative region to the dura mater or the nerve root and results in functional incapacity and pain after laminectomy. Our previous study showed that down-regulation of lncRNA-COX2 is involved in the epidural scar formation. However, it remains unknown whether lncRNA-COX2 participate in the fibroblast activation and epidural fibrogenesis.Methods: LncRNA-COX2 and EGR1 expression were assessed by qRT-PCR and western blotting. Fibroblasts differentiation, proliferation and migration was determined by Collagen I/ɑ-SMA, 5-ethynyl-2'-deoxyuridine (EdU) and Transwell Assay respectively. Luciferase reporter assay was performed for the verification of target of LncRNA-COX2. Laminectomy was performed to establish the model of epidural fibrosis in mice. Epidural scar was evaluated by hematoxylin and eosin (HE) staining and Masson Trichrome staining.Results: Based on the result of transcriptome profiling, we found LncRNA-COX2 was significantly decreased in epidural tissues after laminectomy and in activated fibrotic fibroblasts. In vitro, overexpression of LncRNA-COX2 suppressed epidural fibrogenesis by inhibiting fibroblasts differentiation, proliferation and migration. Mechanistically, LncRNA-COX2 functioned as competing endogenous RNA (ceRNA) of EGR1. Gain of LncRNA-COX2 significantly decreased the expression of EGR1 and showed anti-fibrotic effect while EGR1 was markedly increased after loss of LncRNA-COX2. In vivo, LncRNA-COX2 attenuated laminectomy-induced epidural fibrosis in mice.Conclusion: In summary, the results demonstrated that LncRNA-COX2 showed anti-fibrotic effect by targeting EGR1 and identified LncRNA-COX2 as therapeutic molecule for preventing aberrant epidural fibrosis.

Potential roles of lncRNA-Cox2 and EGR1 in regulating epidural fibrosis following laminectomy.

Epidural fibrosis, one of the common complications after spinal surgery, seriously affects the surgical decompression effect. Effectively inhibiting the fibrous tissue hyperplasia is pivotal to reduce the scar adhesion. Previous studies showed that early growth response 1 (EGR1) is associated with the fibroblast reactivity induced by transforming growth factor-beta (TGF-β) and plays a vital regulatory role in scar formation; however, the upstream targets and mechanisms still remain unclear. In this work, it was found that the level of long non-coding ribonucleic acid (lncRNA)-cyclooxygenase-2 (COX2) was significantly negatively correlated with EGR1 expression and the severity of the scar. Therefore, it was conjectured that lncRNA-COX2 may decrease fibroplasia and scar formation by negatively regulating EGR1. TGF-β was used to activate the embryonic and adult rat fibroblasts. Rats underwent laminectomy to establish the epidural fibrosis model. The changes in the levels of fibroplasia-related genes were measured and analyzed through messenger RNA (mRNA), lncRNA, and micro RNA expression profile chips. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was applied to determine the levels of EGR1 and lncRNA-COX2, and Western blotting was adopted to detect the content of EGR1, collagen I (Col-1), Col-3, and alpha-smooth muscle actin (α-SMA). The scar formation was reflected by hematoxylin and eosin (HE) staining and Masson staining, and the expression level of α-SMA in the scar tissues was measured via immunohistochemistry. Finally, micro-magnetic resonance imaging (MRI) was utilized to examine the different degrees of epidural fibroplasia. It was found that the reactivity of embryonic rat fibroblasts to the TGF-β stimulation was different from that of adult rat fibroblasts. LncRNA-COX2 was highly expressed in the embryonic rat fibroblasts, but lowly expressed in the adult rat fibroblasts, which had negative correlations with the EGR1 level in embryonic and adult rat fibroblasts. In addition, it was revealed that the expression of EGR1 in the adult rat fibroblasts was remarkably higher than that in the embryonic rat fibroblasts after the activation with TGF-β. Meanwhile, the level of lncRNA-COX2 was lowered after the activation, especially in the adult rat fibroblasts. It was discovered in the in-vivo model that the degree of fibroplasia was positively associated with EGR1 level and negatively correlated with lncRNA-COX2 level. The results of this research elucidated that the down-regulation of lncRNA-COX2 is involved in the epidural scar formation and related to the elevated EGR1 level which regulates the activation of fibroblasts and secretion of massive extracellular matrixes, suggesting that lncRNA-COX2 may modulate the role of fibroblasts in scar formation as an upstream action target of EGR1.

MiR‑519d‑3p promotes TGFβ/Smad mediated postoperative epidural scar formation via suppression of BAMBI.

To investigate the role of microRNA (miR)‑519d‑3p in postoperative epidural scar formation and its regulation of the bone morphogenetic protein and activin membrane‑bound inhibitor (BAMBI), miR‑519d‑3p and BAMBI expression levels in the lumbar disc of patients who had undergone laminectomy were detected with reverse transcription‑quantitative polymerase chain reaction and western blotting. The results demonstrated that miR‑519d‑3p expression was significantly increased, whereas BAMBI expression was sharply reduced in the lumbar discs of patients suffering from epidural scars. Subsequently, the miR‑519d‑3p mimic was transfected into primary fibroblasts isolated from epidural scar tissues. Flow cytometric and Cell Countin Kit‑8 analyses indicated that overexpression of miR‑519d‑3p promoted the proliferation of fibroblasts, the production of tumor necrosis factor‑α and interleukin (IL)‑1α, and the expression of typeI collagen(colI), α‑smooth muscle actin (α‑SMA) and fibronectin(FN). Downregulation of miR‑519d‑3p by the miR‑519d‑3p antagomir transfection had the opposite effect. Bioinformatics and luciferase reporter gene analyses demonstrated that BAMBI is a target gene of miR‑519d‑3p: miR‑519d‑3p directly binds to the 3'‑untranslated region of BAMBI mRNA and suppressed BAMBI protein expression. Finally, the pcDNA‑BAMBI vector and BAMBI small interfering RNA were respectively transfected into primary fibroblasts to overexpress and knockdown the BAMBI gene. It was demonstrated that BAMBI overexpression suppressed fibroblast proliferation, TNF‑α and IL‑1α production, and the expression of colI, α‑SMA and FN proteins, whereas, BAMBI knockdown had the opposite effect. In conclusion, it was noted that BAMBI is a target of miR‑519d‑3p and miR‑519d‑3p promotes transforming growth factor β/mothers against decapentaplegic homolog9‑mediated postoperative epidural scar formation via suppression of BAMBI.

A New Grading of Epidural Hematoma or Scar Formation after Posterior Cervical Spine Surgery: Evaluation of Perioperative Related Factors, Distributions, and Clinical Outcomes after Surgery.

Introduction The purpose of this study was to evaluate surgical outcomes using a new grading of postoperative epidural hematoma (EH) or epidural scar formation after posterior cervical spine surgery. Methods Postoperative EH or epidural scar formation after cervical laminoplasty (LP) or posterior decompression and fusion (PDF) were graded into Grades 1-5 by magnetic resonance imaging at 24 hours, 2 weeks, 6 months, and one year after surgery. The patients were divided into the Mild group (Grades 1-3) and the Severe group (Grades 4, 5). Perioperative factors were compared between the two groups at 24 hours after surgery. Distribution of EH or scar formation was investigated according to two surgeries. The recovery rate of Japanese Orthopedic Association (JOA) scores and the improvements of neck disability index (NDI) were compared between the two groups at one year postoperatively. Results Of the postoperative factors, posterior shift of the cervical spinal cord at C4 and C7 significantly differed between the two groups. Patients in the Severe group at 24 hours after surgery (17%) increased to 41% at 2 weeks and subsequently decreased to 16% at 6 months after LP. After PDF, 3% in the Severe group at 24 hours after surgery increased to 15% at 2 weeks and then decreased to 3% at 6 months postoperatively. Only one (3%) patient remained in the Severe group at 1 year after PDF. The recovery rate of JOA score (47.5%) of the patients in the Mild group showed trend larger than that of the Severe group (34.7%) after LP. Preoperative NDI (15.6 points) significantly improved postoperatively to 12.1 points in only the Mild group after LP. Conclusions The patterns of distribution of EH or scar formation did not differ between the two surgical methods. The severity of postoperative scar formation related to surgical outcomes after LP.

Comparison of the effectiveness of vertebral arch replantation and laminectomy in the treatment of mild to moderate isthmic spondylolisthesis

To compare the effectiveness of vertebral arch replantation and laminectomy in the treatment of mild to moderate isthmic spondylolisthesis. The clinical data of 66 patients with isthmic spondylolisthesis treated with vertebral arch replantation or laminectomy between March 2014 and July 2016 were retrospectively analyzed. They were divided into trial group (34 cases, treated with complete replantation of vertebral arch, intervertebral fusion, and internal fixation) and control group (32 cases, treated with laminectomy with intervertebral fusion and internal fixation) according to different surgical methods. There was no significant difference in general data of gender, age, disease duration, lesion segment, Meyerding grade, and preoperative visual analogue scale (VAS) score, Oswestry disability index (ODI) score, Japanese Orthopaedic Association (JOA) score between the two groups ( P>0.05). The operation time, intraoperative blood loss, complications, vertebral arch fusion of trial group, and epidural scar formation of the two groups were recorded. The VAS score, JOA score, and ODI score were evaluated at preoperation, 3, 6, 12 months after operation, and at last follow-up. The effectiveness was evaluated according to HOU Shuxun's criteria. All the patients successfully completed the surgery, without any aggravation of nerve injury, dural tear, infection, etc. There was no significant difference in the operation time between the two groups ( t=0.583, P=0.562), but the intraoperative blood loss was significantly lower in the trial group than that in the control group ( t=2.134, P=0.037). All the 66 patients were followed up 13-18 months (mean, 16.2 months). Postoperative clinical symptoms of all patients were significantly improved. In the control group, 7 cases were found to have symptoms of spinal canal stenosis with postoperative posture changes at 3 months after operation, and 5 cases showed mild lower limb numbness at 18 months after operation. No complication such as infection and nerve injury occurred in other patients. In the trial group, 34 cases of epidural scar tissue were completely blocked outside the replantation vertebral arch, while in the control group, 11 cases of epidural scar tissue invaded the spinal canal. At last follow-up, the fusion rate of intervertebral bone grafting and vertebral arch replantation in the trial group was 100%, and the fusion rate of intervertebral bone grafting in the control group was also 100%. The VAS score, ODI score, and JOA score were significantly improved at each time point after operation ( P<0.01). The ODI score and JOA score of the trial group were significantly better than those of the control group at 3 months after operation and at last follow-up ( P<0.05), and there was no significant difference in scores between the two groups at other time points ( P>0.05). According to HOU Shuxun's criteria, the excellent and good rate was 91.2% in the trial group and 84.4% in the control group, showing no significant difference ( χ 2=1.092, P=0.573). Compared with laminectomy, vertebral arch replantation can better improve postoperative neurological symptoms, maximize the reconstruction of the bone spinal canal, restore the stability of the intraspinal environment, and it is a better surgical method for lumbar isthmic spondylolisthesis.

MMC controlled-release membranes attenuate epidural scar formation in rat models after laminectomy.

Epidural scar formation after laminectomy impede surgical outcomes of decompression. Mitomycin C (MMC) has been demonstrated to have significant inhibitory effects on epidural scar. This study was undertaken to develop an effective MMC controlled-release membrane and to investigate its effects on epidural scar in rat models of laminectomy. A total of 72 rats that underwent laminectomy were divided into three groups. Among them, 24 were treated with mitomycin C-polylactic acid (MMC-PLA) controlled-release membrane, 24 with mitomycin C-polyethylene glycol (MMC-PEG) controlled-release membrane, and no treatment was performed for the remaining 24 rats (control group). In the following 4 weeks, magnetic resonance image (MRI), macroscopic observation, histology and hydroxyproline (Hyp) concentration analysis were performed to explore the effects of these three therapies on epidural scar. MRI revealed a significant reduction of epidural fibrosis in MMC-PLA and MMC-PEG treatment groups, compared with the control group. Histological results also showed that collagen deposition was significantly reduced after being treated with MMC-PLA or MMC-PEG membranes. Likewise, Hyp concentrations of the epidural scar tissue in MMC-PLA and MMC-PEG groups were markedly lower than those in the control group. However, regarding the effects on reducing epidural scar, no significant difference was found between the MMC-PLA and MMC-PEG groups. In conclusion, MMC-PLA and MMC-PEG membranes are safe and effective in reducing fibrosis. Thus, MMC-controlled-release membranes promises to be a potential therapeutic in preventing epidural scar formation after laminectomy.

Remote Cauda Equina Syndrome Due to Overgrowth of Epidural Free Fat Graft: Case Report

Lumbar discectomy is being done in increasing frequency worldwide where formation of epidural scar formation has been known as a common cause of its failure. Application of a free fat graft despite controversies has been widely used to prevent further adhesion and post-laminectomy scarring. Single nerve root compression and cauda equina syndrome due to compressive effect of free fat graft with a few days to weeks after laminectomy is well known early complication of lumbar discectomy. However, late neurological deficit as the result of significant increase of fat graft volume has been not addressed previously in the literature. Herein, the authors present a middle-age man who was admitted with cauda equina syndrome for one day duration developing 11 years after a redo laminectomy for recurrent disc herniation and local stenosis. The MRI obtained urgently revealed significant overgrowth of the free fat graft that had been already used for prevention of scar formation. Piecemeal surgical removal of fat with clearance of the theca and the corresponding nerve roots result in steady but good recovery within a few weeks. To our knowledge, although overgrowth of fat has been reported in other locations, but this is the first example occurring after its application at the site of laminectomy. Therefore, overgrowth of free fat graft should be added to all previously describe unusual complication of lumbar discectomy.

Hemostasis vs. epidural fibrosis?: A comparative study on an experimental rat model of laminectomy

AimThe aim of this study was to evaluate the histopathological and biochemical impact and effectiveness of two hemostatic agents, Ankaferd blood stopper (ABS) and Microporous Polysaccharide Hemospheres (MPH), on epidural fibrosis in an experimental rat laminectomy model. Material and methodsTwenty adult Wistar albino rats were divided into MPH-treated (n=6), ABS-treated (n=6) and control (n=8) groups. Laminectomy of the lumbar spine was performed in all animals and treatment groups were exposed to MPH and ABS while closure was applied in control group as per usual. Epidural fibrosis was evaluated in all groups macroscopically, histopathologically, biochemically and with electron microscopy four weeks later. ResultsStatistically, it was found that MPH-treated group had significantly less epidural fibrosis compared to ABS-treated and control groups. ConclusionWe compared two hemostatic agents for their propensity to cause adhesions in the present study. Our results show that MPH significantly reduces epidural scar formation and dural adhesion in a rat model of laminectomy while ABS increases postoperative fibrosis.

Pentoxifylline Inhibits Epidural Fibrosis in Post-Laminectomy Rats.

BackgroundThe aim of this experimental study was to investigate the effectiveness of intramuscular pentoxifylline in the prevention of postoperative fibrosis.Material/MethodsWe divided 16 adult Wistar albino rats into 2 equal groups: treatment and control. Both groups underwent L1 vertebral total laminectomy to expose the dura. The intramuscular treatment group received pentoxifylline. Four weeks later, epidural fibrosis was studied in both groups using electron microscopy, light microscopy, histology, biochemistry, and macroscopy.ResultsThe evaluation of epidural fibrosis in the 2 groups according to macroscopic (p<0.01) assessment and light microscopy revealed that epidural scar tissue formation was lower in the treatment group compared to the control group (p<0.001) and the number of fibroblasts was also decreased significantly in the pentoxifylline-treated group (p<0.05). More immature fibers were demonstrated in the treatment group by electron microscopy in comparison with the control group. In biochemical analysis, a statistically significant decrease was detected in hydroxyproline, which indicates fibrosis and myeloperoxidase activity, and shows an inflammatory response (P<0.001).ConclusionsSystemic pentoxifylline application prevents postoperative epidural fibrosis and adhesions with various mechanisms. Our study is the first to present evidence of experimental epidural fibrosis prevention with pentoxifylline.

The role and mechanisms of action of SIRT6 in the suppression of postoperative epidural scar formation.

In order to investigate the role which sirtuin-6 (SIRT6) plays in lumbar spinal epidural fibrosis (EF) and scar formation in vitro and in vivo, SIRT6 and transforming growth factor β (TGF‑β) protein levels in the lumbar disc of patients were detected using western blotting in patients who had undergone a laminectomy. The results demonstrated that SIRT6 expression was significantly reduced in the lumbar discs of patients in whom an epidural scar had formed, but the expression pattern of TGF-β2 was much higher. Subsequently, a pcDNA‑SIRT6 expression vector was constructed and transfected into the primary fibroblasts isolated from the epidural scars. Flow cytometric and MTT analyses indicated that overexpression of SIRT6 suppressed the proliferation of the fibroblasts, and TGF‑β2 and interleukin-1α expression, as well as collagen type I (Col I) production. The results of bioinformatics and molecular biological analyses demonstarted that TGF‑β2 was a target of microRNA-21 (miR-21) and SIRT6 overexpression suppressed the levels of TGF-β2 through promoting the expression of miR-21. Finally, by injecting the pcDNA-SIRT6 vector, it was possible to observe that SIRT6 suppressed EF and epidural scar formation in vivo. In conclusion, we noted that SIRT6 suppressed EF and epidural scar formation in vitro and in vivo. It was also noted that SIRT6 overexpression suppressed TGF-β2 levels by promoting the expression of miR-21.

An injectable hydrogel with or without drugs for prevention of epidural scar adhesion after laminectomy in rats

Epidural scarring occurs inevitably in the defect after spinal laminectomy, and thus how to prevent or reduce it becomes a challenging topic. In the present study, an injectable hydrogel and its dexamethasone (DEX)-loaded hydrogel systems were adopted to prevent epidural scarring in a postlaminectomy rat model. The hydrogel system composed of poly(D,L-lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers was a free-flowing sol at room temperature, and spontaneously turned into a semi-solid gel at body temperature. A lumbar 3 total laminectomy was performed on Sprague Dawley (SD) rats, and the efficacy of the injectable hydrogel with or without drugs in preventing epidural scar formation was evaluated via the gross anatomical observation and histological examination at one month post-surgery. The results demonstrate that the use of hydrogel alone reduced epidural scarring significantly, whereas the efficacy of the DEX-loaded hydrogels presented an irregular dose-dependency of drug and even the inappropriate drug doses resulted in the negative results. Therefore, the present study confirms that the PLGA-PEGPLGA hydrogel holds potential as a barrier device to decrease peridural scarring, and reveals that the sustained delivery of the steroid hormone DEX to prevent surgery-related adhesions in the laminectomy defect is complex. Moreover, our in vivo studies also remind the researchers to pay attention to the irregular dose-dependency of the hormone drugs.

An Interlaminotomy New Zealand White Rabbit Model to Evaluate Novel Epidural Strategies

The New Zealand White (NZW) rabbit model is an established animal model for examining surgical methods to prevent epidural scar formation after spine surgery. As most approaches include complete laminectomy of the rabbit vertebra, this procedure is associated with high morbidity and mortality rates. We examined a less invasive technique, the microsurgical interlaminotomy, for testing epidural substance application in the rabbit spine. Surgery was performed in the cadaver rabbit spine to evaluate the approach before performing it in NZW rabbits. All surgical procedures were performed under an operation microscope. Female rabbits with a mean weight of 4770 g ± 240 g were used. Neurologic symptoms were analyzed based on predefined scores. After resection of the spinal process, the caudal part of the upper lamina was resected using a drill and a 1-mm Kerrison punch. The yellow ligament was resected resulting in a dural exposure of ∼ 5 × 10 mm. Eight pilot interlaminotomies were performed on three cadaveric spines to establish the surgical approach. Twenty-one NZW rabbits were then operated on using the interlaminotomy model. Three rabbits (14.3%) died during surgery due to anesthesia-related complications. Two rabbits (9.5%) showed partial paresis of the lower extremities and one (4.8%) a complete paraplegia. The remaining 15 rabbits (71.4%) had an uneventful recovery without neurologic symptoms. The mean surgical duration was 88 +/- 28 minutes. The rabbit interlaminotomy model is associated with few neurologic deficits and a relatively short operating time.

The effect of interference of perlecan expression on generation of type I collagen in epidural scar cells

Objective To investigate the effect of interference of perlecan expression on generation of type Ⅰ collagen in epidural scar cells.Methods Thirty SD male rats,weighing 250 grams and 2 months of age,were subjected to complete posterior lumbar laminectomy on L4-5.The epidural scar tissues were sampled at 20 days postoperatively for cellular culture by adherence.The third passage fibroblasts derived from the cellular culture were randomized into 3 groups (6 samples in each group):group A subjected to interference of perlecan expression by lentivirus mediated shRNA,group B subjected to interference of perlecan expression by lentivirus without shRNA mediation and group C,the blank control.Then hematoxylin-eosin staining (HE) was done to observe the formation of epidural scar and the activity of fibroblasts and the quantity of collagen synthesis.Western Blot and RT-PCR were performed to quantify the expression of perlecan and generation of type Ⅰ collagen after interference by lentivirus mediated shRNA.Comparisons were done between the 3 groups.Results The multiplicity of infection of 100 was the optimal when the cultured cells exhibited normal morphology and clear outline.RT-PCR showed the ratio of absorbance of the target bands of the type Ⅰ collagen RNA to that of the reference bands was 0.043 ± 0.003 in group A,0.473 ±0.011 in group B and 0.475 ± 0.013 in group C.Western Blot showed the ratio of absorbance of the target bands of the type Ⅰ collagen RNA to that of the reference bands was 0.190±0.005 in group A,2.116±0.012 in group B and 2.122±0.009 in group C.There were significant differences between group A and groups B and C regarding the above indexes (P ＜ 0.05).The generation of type Ⅰ collagen in group A was significantly lower than in groups B and C (P ＜ 0.05).Conclusion Since the interference of perlecan expression by lentivirus mediated shRNA can reduce the expression of type Ⅰ collagen in epidural scar fibroblasts,it can be used to inhibit epidural scar formation after laminectomy. Key words: Laminectomy; Cicatrix; Collagen type Ⅰ; Fibroblasts; Perlecan

Percutaneous discectomy: Minimally invasive method for treatment of recurrent lumbar disc herniation

ObjectivesRecurrent lumbar disc herniation has been reported in 5–11% of patients. Revision surgery carries a higher risk of complications due to epidural scar formation and difficulty in identifying the bony landmarks. The present study was conducted to apply an innovative procedure which optimally has lower complications, and decrease the need for major surgery for high risk patients. Patient and methodOur study presents six patients of recurrent herniation after past performed procedures such as microdiscectomy, or a laminectomy and discectomy who were readmitted and treated with APLD (automated percutaneous lumbar discectomy) as the first line. The APLD criteria for patient selection in the present study are those with predominantly leg pain that failed conservative treatment for at least 6 weeks and, after lumbar surgery for at least 6 months at the same level. ResultsFour of the patients have sciatica recovery signs ranging between excellent to good and, two showed no improvement. None of the screened patients in this study developed any serious complications. ConclusionAlthough this is a small series with a short follow up duration, it can be postulated that in the absence of objective evidence of spinal instability, recurrent disc herniation with predominantly leg pain may be treated by APLD as a first line. This can be especially helpful in patients with high risk for anesthesia.

Prevention of anterior scar formation following discectomy with a medishield adhesion barrier: randomized experimental trial

To investigate whether carboxymethylcellulose/polyethylene oxide (CMC/PEO) gel has a protective effect against epidural scar formation anterior to the dura following discectomy. A barrier gel comprised of CMC and PEO (MediShield) was studied as a material to reduce anterior epidural scar formation in a rabbit laminotomy and discectomy model. After laminotomy and disc puncture, the surgical side was either treated with MediShield or used as a surgical control, as determined by random allocation. Two months after surgery, the animals were euthanized, and their lumbar spines were removed in an en bloc excision for pathological evaluation. Scar formation was evaluated as present or absent. The MediShield group contained 12 rabbits, and the control group contained 7 rabbits. Epidural fibrosis was observed in two out of twelve specimens (17%) in the MediShield group and in three of seven (43%) cases in the control group (P=0.305, Fisher's Exact Test). Though it was not statistically significant, we observed a difference between the MediShield and control group that favored the MediShield group. The application of the CMC/PEO gel might protect against epidural fibrosis after lumbar discectomy, but its efficacy needs to be investigated in larger experimental trials.

Remarkable epidural scar formation compressing the cervical cord after osteoplastic laminoplasty with hydroxyapatite spacer

The authors report on an 81-year-old woman whose condition deteriorated 2 months after undergoing osteoplastic laminoplasty with placement of hydroxyapatite spacers. Magnetic resonance imaging showed postlaminectomy scar formation compressing the cervical spinal cord. The patient underwent laminectomy and removal of remarkably thick epidural scar tissue, which resulted in resolution of her symptoms. Histological diagnosis of the scar was fibrous granulation tissue with foreign body granuloma, characterized by multinucleated giant cells and marked increases of capillary vessels, fibroblasts, and collagen fibers. This case of symptomatic postlaminectomy scar formation after osteoplastic laminoplasty suggests that osteoplastic laminoplasty cannot always prevent laminectomy membrane formation.

Application of liposome-encapsulated hydroxycamptothecin in the prevention of epidural scar formation in New Zealand white rabbits

Background context Epidural adhesion and fibrosis attribute to the prevalence of pain in normal wound healing after laminectomy surgery. Hydroxycamptothecin (HCPT), an antitumor drug, has proved to be effective in preventing fibroblast proliferation and reducing epidural adhesion after laminectomy in vivo animal study. However, HCPT’s disadvantages, such as poor solubility and short half-life, limit its application clinically. Compared with HCPT, the liposome-encapsulated HCPT (L-HCPT) could reduce epidural fibrosis by preventing the proliferation of fibroblast in the scar tissues with longer half-life and increased solubility. Purpose To evaluate the suitability of L-HCPT in the laminectomy models on rabbits and to explore the mechanisms in the prevention of epidural scar formation. Study design An original investigation that characterizes the novel delivery system in the combinational application of HCPT and liposome (L-HCPT). Patient sample The sample comprises 24 mature New Zealand white adult rabbits. Methods Lumbar laminectomies at L4 and L6 with an L5 disc injury were performed on 24 mature New Zealand white adult rabbits. The rabbits were then randomized into three groups. In Group I, the laminectomy site was treated with a cotton pad soaked with HCPT solution (1 mg/mL) for 5 minutes (HCPT group) and was flushed with saline completely. In Group II, 1 mL of L-HCPT was seeded on the laminectomy area (L-HCPT group). In Group III, the laminectomy area was flushed with saline before wound closure (control group). After 28 days, the animals underwent magnetic resonance imaging. The animals were euthanized; the spinal section was removed for macroscopic evaluation, and hydroxyproline in the scar tissue was quantified. Results Operation in all the animals yielded a reproducible laminectomy, without complication or mortality. In the laminectomy sites treated with L-HCPT, the dura mater was clean without any evident adhesion. Magnetic resonance imaging analysis implied that L-HCPT treatment could reduce the epidural scar significantly compared with saline control group, which was further proved by the decreased concentration of hydroxyproline in the scar tissues. Conclusion These results demonstrate that the treatment of postlaminectomy wounds in rabbits with L-HCPT reduces the severity of adhesion.

The effect of methylene blue on peridural fibrosis formation after laminectomy in rats: an experimental novel study

Background context Despite progress in surgical techniques, some patients still face postoperative recurrence of pain, although the rate of successful outcomes is estimated to be approximately 70% and 86% after primary decompression spinal surgery. Recently, attention has been focused on peridural fibrosis (PF), which may be responsible for recurrent pain after laminectomy or discectomy. Methylene blue (MB) has been shown to prevent fibrosis formation in various tissues. Purpose The aims of this study were to investigate the effects of MB and assess the effects of different doses on the prevention of postlaminectomy fibrosis formation in a rat model. This preclinical model is a potential platform for future clinical trials to identify an effective agent for the prevention of clinically important epidural scar formation. Study design An established bilateral L5–L6 rat laminectomy model was used to evaluate postlaminectomy PF with macroscopic and microscopic analyses. Patient sample Seventy-five male adult white Sprague-Dawley rats that underwent laminectomy at the L5–L6 levels were divided into five groups of 15 rats each. Outcome measures Dissected specimens were evaluated macroscopically and microscopically by examiners who were unaware of the group assignment to record the presence or absence of PF formation. Methods Groups A and B served as controls and Groups C, D, and E received treatment. Group A (sham) underwent laminectomy, and Group B was treated with normal saline at the laminectomy site. Rats in Groups C, D, and E received 0.1 mL MB at concentrations of 0.5%, 1%, and 2%, respectively, at the laminectomy site. All rats were killed 4 weeks after laminectomy. The results were compared statistically with the nonparametric Kruskal–Wallis test and Poisson regression. Results Peridural fibrosis was found in five rats (33%) in control Groups A and B and in two rats (10%) in MB-treated laminectomy Groups C and D. The difference between control and MB groups was not statistically significant (p=.27). The preventive effect of MB on PF was not seen at the highest dose of MB (2%) in Group E. Severity of fibrosis was lower in Groups C (MB 0.5%) and D (MB 1%) than in Group E (MB 2%) (p<.01). Wound healing was not affected, and there was no cerebrospinal fluid leakage. No neurological deficits were seen. Conclusion Low doses of MB may be an effective agent in preventing PF formation after lumbar laminectomy in rats. Clinical significance and safety in human use are currently undetermined.

Preparation and characterization of a new gellan gum and sulphated hyaluronic acid hydrogel designed for epidural scar prevention

Postsurgical adhesions are a common problem in clinical practice, causing nerve compression, pain and discomfort. A new hydrogel based on gellan gum and sulphated hyaluronic acid was synthesized, with the aim to create an effective barrier for epidural scar formation. Physico-chemical properties of the gel were analyzed, and preliminary biocompatibility data (i.e. cytotoxicity) have been collected in view of its potential clinical use. The characterization of the new material demonstrated that the hydrogel, due to its high-viscosity, could effectively act as a barrier with a long in situ residence time. In addition, the hydrogel can be easily extruded from a syringe and its structure exhibits excellent stabilizing properties. Furthermore, biological assays showed that this gel is suitable for further preclinical development.