| BACKGROUND CONTEXT:Epidural scar, also known as epidural fibrosis, is the scar or tissue fibrosis formed in the epidural space after surgery, which is the body's repair response to injury. Postoperative epidural fibrosis which adheres to lumbar nerve root is considered as an important reason for the failure of surgery, badly influencing the surgical results and prognosis. So, the control of scar formation has been one of the main concerns in spine surgery. Limited operation, reducing stimulation to tissues in and around the spinal canal and diminishing the extend and scope of injury, and completely clear off exutive tissues, avoiding foreign body left, lowering degree of inflammatory response within the spinal canal and controlling inflammation process are the most basic and important measures to reduce the proliferation and adhesion of scar tissues in the spinal canal. Poly-lactic acid membrane is able to reduce adhesion of dura mater to surrounding tissue and with the absorption of poly-lactic acid membrane a potential gap between dura mater and surrounding tissue is formed, effectively inhibiting the formation of scar. However, poly-lactic acid membranes are planar structures. It can't surround the dura mater and nerve roots in three-dimensional perspective, only reducing the adhesion of dural mater to posterior tissues, which greatly limits the effect of preventing adhesion. Mitomycin belongs to chemotherapy drugs, which has positive effect on inhibiting cell proliferation. However, its cytotoxicity and the administrative pathway prevents its application. Therefore, we designed a new controlled-release delivery system which consisted of mitomycin and poly-lactic acid and used in spinal surgery between the dura mater and the surrounding tissue. There are several benefits. Firstly, the presence of poly-lactic membrane makes the dura mater isolated from the surrounding tissue and hematoma. Secondly, as the degradation of polylactic acid film, mitomycin is released around the surgical area and inhibits the proliferation of fibroblast and formation of matrix, preventing postoperative adhesion of dura mater and nerve roots in three-dimensional perspective.PURPOSE:Our purpose is to design and attest the role of new delivery system MMC-PEG controlled-release film in preventing the epidural scar adhesions after laminectomy in the rat model and inhibiting effectively proliferation of fibroblast in vitro.STUDY DESIGN/SETTING:A total laminectomy of L1 in the rat model was employed to assess epidural fibrosis between and around the spinal nerves using a histochemistry assessment along with flow cytometry analysis.PATIENT SAMPLE:SpragueDawley.OUTCOME MEASURES:Macroscopic evaluation, histological analysis and flow cytometry analysis.METHODS:1.the prepare and test of MMC-PEG:The mitomycin C, sorbic acid, polyvinyl alcohol-124, glycerin, purified water were prepared on pro-rata allocation, which then underwent steam sterilization and were converted into film and dried. Finally, the concentration of MMC was calculated through high-performance liquid chromatography.2. Lumbar laminectomies at L1 and L2 with a L1-L2 disc injury were performed on 64 adult male Sprague-Dawley rats. The rats were then randomized into four groups. In Groupâ… ,25 mg PEG film was applied on the dura mater and mutifidus in the laminectomy area before the layers were sutured. In Group â…¡, a cotton pad soaked with 0.05% MMC solution was kept on the laminectomy area for 5 minutes. In Groupâ…¢,25 mg PEG film containing 0.01% MMC was implanted on the laminectomy area. In Groupâ…£, the laminectomy area was flushed with saline before wound closure.3. The rats were executed 4 weeks after the operation. Macroscopic evaluation and histological analysis of epidural scar adhesion with the HE stain and Masson stain were employed followed by the quanitification of hydroxyproline and flow cytometry analysis of the apoptosis of fibroblasts in the scar tissues.4. The SD rat fibroblasts were cultured in vitro and fibroblast apoptosis was analyzed using MTT method and flow cytometry analysis.RESULTS:The average concentration of mitomycin C in the controlled-release MMC-PEG film was 0.096%. The recovery of all rats was uneventful after the operations. In the laminectomy sites of rats treated with MMC or MMC-PEG, the dura mater was clean without any evident adhesion or membrane. Collagen tissue hyperplasia significantly decreased in the MMC or MMC-PEG treated models. Accordingly, hydroxyproline concentration was significantly reduced in these two groups compared with saline-control group. And the apoptosis of fibroblasts, however, was significantly elevated in the MMC or MMC-PEG group compared with saline-control group.CONCLUSIONS:These results demonstrate that the treatment of postlaminectomy wounds with MMC-PEG film reduces the severity of adhesion by decreasing the concentration of hydroxyproline and increasing the apoptosis of fibroblasts. |
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