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SEM observation of PCL fibrous membranes (a), PCL-2%-CEL fibrous membrane (b), and PCL-6%-CEL fibrous membrane (c). The cumulative release profiles of CEL-loaded PCL fibrous membranes (d).
Source publication
To date, failed back surgery syndrome (FBSS) remains a therapy-refractory clinical condition after spinal surgery. The antiadhesion membrane is applied to prevent FBSS by isolating fibrosis; however, the inflammation stimulated by the foreign body and surgical trauma needs to be further resolved simultaneously. Therefore, we developed new electrosp...
Citations
... Chronic inflammation plays an important role in the induction of dural fibrosis, wound healing, and pain sensitization. The local inflammatory response is a complex pathological process, which not only produces pain-inducing inflammatory mediators but also accelerates the formation of dural fibrosis [28]. Previous studies have suggested that inflammation-related arachnoiditis, rather than mechanical compression, may be an important pathological mechanism of CPSS [28]. ...
... The local inflammatory response is a complex pathological process, which not only produces pain-inducing inflammatory mediators but also accelerates the formation of dural fibrosis [28]. Previous studies have suggested that inflammation-related arachnoiditis, rather than mechanical compression, may be an important pathological mechanism of CPSS [28]. Clinical evidence has shown that numerous inflammatory mediators, including IL-6, IL-8, and prostaglandin E2 (PGE2), have been found in wound drainages in patients who have undergone spinal surgery [29]. ...
... Certain materials can also act as carriers to control local drug release [18]. For example, electrospun polycaprolactone (PCL) fibrous membranes loaded with celecoxib (CEL) induced a slow release of CEL for 2 weeks and attenuated fibrosis and inflammation associated with CPSS in rats [28]. ...
Chronic pain after spine surgery (CPSS) is often characterized by intractable low back pain and/or radiating leg pain, and has been reported in 8–40% of patients that received lumbar spine surgery. We conducted a literature search of PubMed, MEDLINE/OVID with a focus on studies about the etiology and treatments of CPSS and low back pain. Our aim was to provide a narrative review that would help us better understand the pathogenesis and current treatment options for CPSS. This knowledge will aid in the development of optimal strategies for managing postoperative pain symptoms and potentially curing the underlying etiologies. Firstly, we reviewed recent advances in the mechanistic study of CPSS, illustrated both structural (e.g., fibrosis and scaring) and non-structural factors (e.g., inflammation, neuronal sensitization, glial activation, psychological factor) causing CPSS, and highlighted those having not been given sufficient attention as the etiology of CPSS. Secondly, we summarized clinical evidence and therapeutic perspectives of CPSS. We also presented new insights about the treatments and etiology of CPSS, in order to raise awareness of medical staff in the identification and management of this complex painful disease. Finally, we discussed potential new targets for clinical interventions of CPSS and future perspectives of mechanistic and translational research. CPSS patients often have a mixed etiology. By reviewing recent findings, the authors advocate that clinicians shall comprehensively evaluate each case to formulate a patient-specific and multi-modal pain treatment, and importantly, consider an early intraoperative intervention that may decrease the risk or even prevent the onset of CPSS.
Translational potential statement
CPSS remains difficult to treat. This review broadens our understanding of clinical therapies and underlying mechanisms of CPSS, and provides new insights which will aid in the development of novel mechanism-based therapies for not only managing the established pain symptoms but also preventing the development of CPSS.
... Their hypothesis was confirmed by the reduced type I and type III collagen expression. In 2021, celecoxib was also used in a PCL electrospun nanofibrous membrane for the treatment of failed back surgery syndrome with similar results of anti-inflammatory response [189]. ...
A flexor tendon injury is acquired fast and is common for athletes, construction workers, and military personnel among others, treated in the emergency department. However, the healing of injured flexor tendons is stretched over a long period of up to 12 weeks, therefore, remaining a significant clinical problem. Postoperative complications, arising after traditional tendon repair strategies, include adhesion and tendon scar tissue formation, insufficient mechanical strength for early active mobilization, and infections. Various researchers have tried to develop innovative strategies for developing a polymer-based construct that minimalizes these postoperative complications, yet none are routinely used in clinical practice. Understanding the role such constructs play in tendon repair should enable a more targeted approach. This review mainly describes the polymer-based constructs that show promising results in solving these complications, in the hope that one day these will be used as a routine practice in flexor tendon repair, increasing the well-being of the patients. In addition, the review also focuses on the incorporation of active compounds in these constructs, to provide an enhanced healing environment for the flexor tendon.
... For example, cross-linked hyaluronic acid gel decreases epidural adhesion by suppressing inflammation 12 and increasing the production of matrix metalloproteinases 13 . Similarly, electrospun membranes loaded with anti-adhesive drugs (mitomycin C, meloxicam, and celecoxib) effectively reduced scarring formation after spine operation 14,15 . Mitomycin C is an alkylating chemotherapeutic agent in cancer. ...
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.
... 2 Epidural adhesion is considered the most common cause of FBSS and involves various degrees of inflammatory infiltration, scar tissue formation, and tissue adhesions in the epidural space. 3 Although improved surgical methods and drug therapy regimens can exert a degree of control over FBSS, they have limited clinical effects. 4 Recently, with advances in nanomaterials, antifibrotic nanofiber membranes (NFm) have been used to cover the spinal dura mater as a barrier, offering a reliable therapeutic option for halting epidural adhesion and reducing the risks of developing FBSS events. ...
Background
The frequent occurrence of failed back surgery syndrome (FBSS) seriously affects the quality of life of postoperative lumbar patients. Epidural adhesion is the major factor in FBSS.
Purpose
A safe and effective antiadhesion material is urgently needed.
Methods
A superhydrophilic PLGA-g-PVP/PC nanofiber membrane (NFm) was prepared by electrospinning. FTIR was performed to identify its successful synthesis. Scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, and water contact angle measurement were performed. CCK-8 assays were performed in primary rabbit fibroblasts (PRFs) and RAW264.7 cells to explore the cytotoxicity of PLGA-g-PVP/PC NFm. Calcein-AM/PI staining was used to measure the adhesion status in PRFs. ELISA was performed to measure the concentrations of TNF-α and IL-10 in RAW264.7 cells. In addition, the anti-epidural adhesion efficacy of the PLGA-g-PVP/PC NFm was determined in a rabbit model of lumbar laminectomy.
Results
The PLGA-g-PVP/PC NFm exhibited ultrastrong hydrophilicity and an appropriate degradation rate. Based on the results of the CCK-8 assays, PLGA-g-PVP/PC NFm had no cytotoxicity to PRFs and RAW264.7 cells. Calcein-AM/PI staining showed that PLGA-g-PVP/PC NFm could inhibit PRF adhesion. ELISAs showed that PLGA-g-PVP/PC NFm could attenuate lipopolysaccharide-induced macrophage activation. In vivo experiments further confirmed the favorable anti-epidural adhesion effect of PLGA-g-PVP/PC NFm and the lack of a strong inflammatory response.
Conclusion
In this study, PLGA-g-PVP/PC NFm was developed successfully to provide a safe and effective physical barrier for preventing epidural adhesion. PLGA-g-PVP/PC NFm provides a promising strategy for preventing postoperative adhesion and has potential for clinical translation.
Background context:
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.
Purpose:
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.
Study design/setting:
Systematic Review METHODS: According to the PRISMA guidelines, we systematically reviewed the literature in October 2022. The exclusion criteria included duplicates, non-relevant articles, and insufficient detail of drug mechanism.
Results:
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 anti-angiogenesis. In addition, we summarized various pathways to prevent epidural fibrosis.
Conclusion:
This study allows a comprehensive review of pharmacotherapies to prevent epidural fibrosis during laminectomy.
Clinical significance:
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.
