Temperature-sensitive hydrogel loaded with DNase I alleviates epidural fibrosis in a mouse model of laminectomy

Excessive epidural fibrosis attached to the dura mater is the major cause of recurrent failed back surgery syndrome after spine surgery. Neutrophil extracellular traps (NETs) promote epidural fibrosis, raising the possibility that the DNA backbone of NETs may be a potential target in the therapy of epidural fibrosis. Human body temperature-sensitive hydroxypropyl chitin hydrogel solutions were prepared to encapsulate DNase I, which gradually decomposed in vivo. DNase I, which was released from temperature-sensitive hydrogels, destroyed the DNA backbone of NETs and dispersed the clustering of myeloperoxidase (MPO) in NETs. Evidence from MRI, H&E and Masson staining supported that hydroxypropyl chitin hydrogels loaded with DNase I were nontoxic and reduced epidural fibrosis. As expected, fibronectin in the wound was significantly abridged in the mice treated with hydrogels loaded with DNase I. Compared with the gelatin sponge absorbing DNase I, temperature-sensitive hydroxypropyl chitin hydrogels loaded with DNase I were more powerful in the therapy of epidural fibrosis. These results indicate that temperature-sensitive hydroxypropyl chitin hydrogels were effective in DNase I encapsulation and alleviation of epidural fibrosis in a mouse model of laminectomy.

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<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.

Quercetin Inhibits Rat Epidural Fibrosis by Regulating the Biological Behavior of Fibroblasts

Objective: This study attempted to investigate the effects of quercetin on postoperative fibrosis in the epidural as well as any potentially relevant signaling pathways.Methods: The effect of quercetin on reducing epidural fibrosis was confirmed via histological staining and immunohistochemical analysis in vivo. Accordingly, cell counting kit-8 (CCK-8), Western blot analysis, immunofluorescence and Eedu staining, TUNEL staining and transmission electron microscopy were used to detect the effects of quercetin on the proliferation and apoptosis of fibroblasts and explore the possible signal transduction pathway.Results: HE staining and Masson staining showed that quercetin could reduce the number of fibroblasts and collagen content. Moreover, LC3 immunohistochemical staining demonstrated that quercetin could induce autophagy, while CCK-8 showed that quercetin inhibited fibroblast viability in a concentration and time-dependent manner. The results of Edu staining, TUNEL staining and Western blot illustrated that quercetin could inhibit the proliferation and promote the apoptosis of fibroblasts. Additionally, immunofluorescence showed that quercetin could inhibit the migration of fibroblasts and reduce collagen content. LC3 immunofluorescence staining, Western blot and transmission electron microscopy demonstrated that quercetin could induce autophagy. Furthermore, following intervention with autophagy inhibitor 3-MA, quercetin was suggested to affect the proliferation and apoptosis of fibroblasts via autophagy, possibly through the PI3K / Akt / mTOR signaling pathway.Conclusion: Quercetin can regulate fibroblast proliferation, apoptosis, migration and other biological behaviors through autophagy, thereby preventing epidural fibrosis. The specific corresponding pathway may be the PI3K / Akt / mTOR signaling pathway.

Effect of Cerebrospinal Fluid on Fibroblasts Concerning Epidural Fibrosis: An In Vitro Study

One of the most common treatments for lumbar disc herniation and other lumbar disorders is lumbar laminectomy. There may be some unwanted and serious complications with this procedure such as the “failed back surgery syndrome (FBSS)”. Epidural fibrosis (EF), mainly due to fibroblast proliferation, emerges as the main cause of failed back surgery syndrome. According to the current literature and practice techniques, different agents are being used to prevent EF formation. To date there is no single agreed upon treatment method of EF. In this study, dilutional effect of CSF, together with low potassium levels, on primary skin fibroblast cultures was studied as a possible material for EF prevention. CSF at different concentrations (0-100%) were tested to see its effect on Skin fibroblast proliferation. A wound healing assay was also performed to see the effect of CSF on wound healing. The cell proliferation goes up from 24h to 72hr in all CSF percentages from 0-75% but the proliferation was inhibited at 100% CSF. The “wound” is closed successfully in all CSF percentages between 0-75. The 100% CSF fails to completely close the wound. Adverse effects of low concentrations of potassium levels and dilutional effect of CSF may be a promising solution in the prevention of EF. Further in vivo and in vitro experiments are required to characterize its use.