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.

Excessive production of epidural fibrosis in the nerve root can be a pain source after laminectomy. Pharmacotherapy is a minimally invasive treatment option to attenuate epidural fibrosis by suppressing proliferation and activation of fibroblasts, inflammation, and angiogenesis, and inducing apoptosis.
We reviewed and tabulated pharmaceuticals with their respective signaling axes implicated in reducing epidural fibrosis. Additionally, we summarized current literature for the feasibility of novel biologics and microRNA to lessen epidural fibrosis.
Systematic Review.
According to the PRISMA guidelines, we systematically reviewed the literature in October 2022. The exclusion criteria included duplicates, nonrelevant articles, and insufficient detail of drug mechanism.
We obtained a total of 2,499 articles from PubMed and Embase databases. After screening the articles, 74 articles were finally selected for the systematic review and classified based on the functions of drugs and microRNAs which included inhibition of fibroblast proliferation and activation, pro-apoptosis, anti-inflammation, and antiangiogenesis. In addition, we summarized various pathways to prevent epidural fibrosis.
This study allows a comprehensive review of pharmacotherapies to prevent epidural fibrosis during laminectomy.
We expect that our review would enable researchers and clinicians to better understand the mechanism of anti-fibrosis drugs for the clinical application of epidural fibrosis therapies.

BACKGROUND: Amniotic membrane tissue has been thought to potentiate healing in many soft tissue conditions. Specifically, recent studies have shown its therapeutic potential for treatment in the setting of spinal pathologies. The purpose of this study is to thoroughly review the existing scientific literature and evidence concerning the clinical use of amniotic membrane-derived biologic agents on postoperative outcomes following spinal surgery.
METHODS: A systematic review was conducted following preferred reporting items for systematic reviews and meta-analyses guidelines using PubMed, Embase, and Cochrane databases up to December 2020 to identify animal and clinical studies examining the therapeutic potential for amniotic membrane tissue in the setting of spinal pathologies (including disc herniation, prevention of epidural fibrosis, and spinal fusion). Studies were broken down into 2 categories: experimental model type and the type of amnion product being analyzed.
RESULTS: A total of 12 studies (4 clinical studies and 8 studies utilizing animal models) met inclusion criteria. Additionally, the major types of amnion product were divided into cryopreserved/freeze-dried amniotic membrane, human amniotic fluid, human amniotic membrane, cross-linked amniotic membrane, and amnion-derived epithelial cells. While heterogeneity of study design precludes definitive specific results reporting, most studies showed positive benefits on healing/outcomes with amniotic augmentation. Specifically, amnion products have shown promising effects in reducing epidural adhesions and scar tissue after spine surgery, improving spinal fusion rate and postoperative pain scores, and promoting better functional outcomes after spine surgery.
CONCLUSIONS: A review of the limited number of reported studies revealed a wide variety of amniotic membrane preparations, treatment regimens, and indications, which limit definitive conclusions. To date, while there is no definitive clinical proof that amniotic tissues enhance tissue repair or regeneration, the aggregate results demonstrate promising basic science and outcomes potential in spinal surgery. Further study is warranted to determine whether this application is appropriate in the clinical setting.
CONCLUSIONS: This systematic review provides a summary of the existing literature regarding the use of amniotic membrane preparations, treatment regimens, and indications within spinal surgery. With the growing popularity and utilization of biologic agents such as amniotic membrane-derived products in orthopedic and neurologic surgery, this systematic review gives physicians a concise summary on the outcomes and indications associated with amniotic membrane products.
METHODS:

Spinal cord stimulation is a safe method for treating chronic pain syndromes. Spinal cord stimulators can be placed either surgically by creating a laminectomy defect for paddle leads or percutaneously by inserting electrodes. They are usually not associated with major complications. There have been several reports of epidural fibrosis formation after paddle lead placement but only 1 case of excessive fibrosis following percutaneous lead placement. We describe the unique case of excessive cervical fibrosis formation with creation of tolerance phenomenon, clinically significant stenosis, cord compression, and myelopathy after percutaneous lead placement, which improved after surgical removal of the implant. We also reviewed the PubMed and Medline databases for all cases of significant epidural fibrosis related to spinal cord stimulator lead placement, including both surgically implanted paddles and percutaneously implanted leads. This is an uncommon complication after placement of spinal cord stimulators, but it can carry a clinically significant impact and be the source of severe morbidity. It should especially be suspected if the successful placement of the device is followed by development of a \"tolerance\" phenomenon, with progressive loss of satisfactory pain control and development of new myelopathic symptoms.