Postoperative epidural fibrosis and adhesion are common occurrences during the healing process of injured tissue after a spinal operation. Postoperative epidural, peridural, or perineural adhesions after a laminectomy frequently results in failed spinal surgeries122). A large number of patients also experience a recurrence of pain after spinal decompression surgery7202932). Consequently, approximately 19% of surgical patients undergo at least one additional spine operation within 5 years after the initial spinal operation45), while as few as 65% of patients return to normal daily activities and only 61% return to work after spinal surgery3). Most of these patients undergo additional surgical procedures because of the development of new musculoskeletal and radicular symptoms29). The operation time length and the incidence of iatrogenic nerve root damage and dural tears are often increased in these patients due to technical difficulties arising from the presence of epidural fibrosis or adhesion tissue from their initial surgeries212449).

Many factors have been suggested as triggers of adhesion formation, including foreign materials (e.g., starch, surgical gloves, and suture materials), infection, and duration of surgery952). However, even the careful management of these factors has not reduced the rate of adhesion occurrence. Tissue hypoxia can also induce adhesion formation40); a routine spinal surgery incision that interrupts blood circulation can produce hypoxia52), which alters the phenotype of normal fibroblasts to adhesion fibroblasts39) and triggers superoxide production and inflammation19), thus leading to postoperative adhesion.

Surgeons rely on several classic strategies for adhesion prevention or reduction. For example, they avoid the use of powdered gloves; minimize tissue handling and trauma; use sufficient irrigation; minimize the use of electro-coagulation; perform meticulous hemostasis; use small, biocompatible suture materials; and avoid desiccation of the tissue273447). However, these surgical strategies are not completely effective. Various treatments, such as the use of low-dose irradiation, non-steroid anti-inflammatory drugs (NSAIDs), and steroids, have been tested for their ability to reduce peridural adhesion after spinal surgery121417). The use of physical barriers has also been reported, including nonbiological synthetic membranes and forms, as well as free or pedicle fat grafts61011284248).

Physical barriers rely on a separation of the injured tissue surface from adjacent tissues as the basic mechanism for the prevention of epidural adhesion41). Numerous studies have employed physical barrier methods to prevent postoperative tissue adhesion10111625282935363748), but sufficient anti-adhesion effects can only be achieved if the barrier is placed between the dura and its surrounding tissues for an adequate amount of time, and after the healing process is complete, the barrier must be resolved or absorbed naturally into the body, rather than remaining as a foreign body. The barrier material must also be nontoxic while it is in the body2551).

Guardix-SG® (Genewel, Dongsung Company, Seongnam, Korea) is a poloxamer-based, temperature-sensitive, anti-adhesive agent (TSAA agent)183536). This TSAA agent is a complex consisting of crosslinked poloxamer, alginate, and CaCl₂, that overcomes the most critical fault of poloxamer as a barrier material-absorption by the body before an anti-adhesion effect can occur43). Notably, this TSAA agent also has the ability to transform from a solution to a gel form at body temperature, which enhances its properties as a physical barrier (Fig. 1). The purpose of this study is to examine the efficacy of the TSAA agent as a mechanical barrier for the prevention or reduction of peridural scar adhesion in a rabbit laminectomy model.

The general condition of all rabbits remained good after surgery, with no cases of postoperative paralysis or infection noted. As a result, the control group (for whom the defect was left empty and covered by a re-approximation of soft tissue and skin at the laminectomy site) and the experimental group (for whom 2 mL of the TSAA agent was applied to the dura) each consisted of 26 samples (Fig. 6, 7, Table 1).

Postoperative peridural adhesion causing compression or tethering of the nerve root has been proposed as one of the possible factors leading to a poor clinical outcome after a successful laminectomy3238). After surgery, some patients show increased susceptibility to recurrent disc herniation or stenosis because of scar tissues that may restrict nerve root mobility42). The relationship between clinical symptoms and adhesion formation is still unclear, but peridural scar adhesion is attributed to as many as 24% of all failed back surgery cases38).

The precise mechanism of postoperative peridural adhesion is not clear. LaRocca and McNabb26) have reported that epidural and peridural adhesion, forming a membrane called the laminectomy membrane, is caused by a posterior invasion of fibroblasts from the erector spinal muscles. Songer et al.45) have proposed that epidural fibrosis arises from replacement of the epidural fat by a hematoma. The absorption of the hematoma then leads to replacement with granulation tissues, which mature into dense fibrotic tissue. However, regardless of the exact mechanism of formation of postoperative peridural adhesions, preventing or limiting fibroblast proliferation from coming into contact with the exposed dura in the early healing phase seems to be a key factor in preventing adhesion formation842). In other words, postoperative peridural adhesion occurs following a proliferation of fibroblasts and biosynthesis of collagen and the extracellular matrix.

Many previous studies have used experimental animal models to determine the efficacy of various anti-adhesive agents for the prevention or reduction of adhesion10111625282935363748). For example, Songer et al.4445) have shown that the anti-adhesive agent sodium hyaluronic acid solution greatly reduced scar formation after a laminectomy and discectomy in a dog model. They found less fibrosis and thinner collagen layering around the nerve roots and dura in histological sections. The current study assessed the effects of the TSAA agent, Guardix-SG® compared with an untreated group by utilizing the rabbit laminectomy model used in several previous studies and found that the thickness of the dura was significantly less and the distance from the surface of dura to the scar tissues was greater in the TSAA agent treatment group than in the untreated group.

Peridural adhesion after spinal surgery ultimately results in the release of vasoactive factors at the damage site and induces accumulation of inflammatory cells, thereby inducing the formation of collagen-rich vessels and infiltration of fibroblasts, macrophages, and giant cells. Gradually, the normal tissue is substituted by angiogranular tissue and the adhesion becomes permanent16). The current study has identified a significantly lower concentration of collagen in the experimental group than in the control group. The number of inflammatory cells was not significantly different in the two groups at postoperative 6 weeks, although the mean number of inflammatory cells was relatively lower in the experimental group than in the control group. These results suggest that the swelling of the dura or spinal cord due to inflammation was reduced by the TSAA agent treatment and that the TSAA agent effectively prevented invasion by scar tissue. Additionally, based on the observations of the rabbit histological sections, this study has indicated that treatment with the TSAA agent has several advantages. First, because the TSAA agent is a sterile, absorbable gel matrix, it is non-toxic and does not induce granuloma formation. Second, the anti-fibrotic properties of the TSAA agent are localized to the discrete area to which it is applied, so healing of the adjacent tissue is not significantly affected. No damage to the skin, the subcutaneous tissue, or the muscle was identified in the present study-the use of the TSAA agent primarily resulted in the prevention scar formation and adhesion adjacent to the dura at the laminectomy site.

As previously stated, histological sections were obtained at postoperative 6 weeks in this study. An experimental period of 6 weeks is short for evaluating the degree of peridural adhesion, but the formation of dense fibrosis at the laminectomy site at least 4 weeks postoperatively in rabbits is a reliable finding46). In addition, previous studies have reported that significant bone regeneration can be seen about 9 weeks postoperatively in rabbit models46). Therefore, this study limited the experimental period of peridural adhesion to only 6 weeks to eliminate the confounding bias of bone growth. In addition, in current study, the L3 laminectomy site only was used in the control group and the L6 laminectomy site only was used in the experimental group. Rabbits are quadrupeds with seven vertebrae. Because the difference is at least between the upper lumbar and lower lumbar in the quadrupeds, which is different from bipeds, different levels within same animal were used for the control and experimental groups23).

In general, physical barriers, such as anti-adhesive agents, prevent adhesion after a laminectomy by a basic mechanism that involves the separation of the surrounding injured tissue surface from the adjacent dura membrane41). Many kinds of biological and nonbiological materials have been tested since LaRocca and McNabb first published the use of the laminectomy membrane in 197461011162528293536374248). Among these, suitable materials for clinical use are film, solution, gel, and the recently developed sol-gel transition-type barriers. The film-type barrier is easily handled and can be cut into a shape that fits the form of the exposed area. However, the most critical disadvantage of the film barrier is potential reduction of the anti-adhesive effects because this type of barrier cannot ensure complete coverage of nerves in the marginal area after laminectomy and can cause the proliferation of fibrous tissue in gaps between the barrier and the tissues1531). The solution-type barrier can be easily applied to surgery irrespective of the shape of the exposed laminectomy site, and it overcomes the concerns regarding incomplete coverage of the nerves in the marginal area. However, it cannot be fixed onto the surgical site due to flow to other regions and can be drained too early by drainage catheters before adhesion can be prevented233). The gel-type barrier can cover almost the whole site of the nerves in the marginal area regardless of the shape of the exposed laminectomy site because of its high shape-molding capacity or shape-filling effect. The disadvantage of the gel type is that the material is relatively difficult to handle251).

The current study investigated the effectiveness of the TSAA agent, Guardix-SG® developed to remedy the shortcomings of the existing types of anti-adhesive agents. This TSAA agent is a complex of CaCl₂, alginate, and poloxamer. Alginate, a hydrogel form extracted from seaweed, is commonly used clinically36). A previous study by Nagakura et al.30) demonstrated that a pure viscous injectable alginate solution reduced scar formation by forming a physical barrier against fibroblast invasion and that it also stimulated wound healing in the surrounding tissue. Poloxamer, a complex of nonionic triblock copolymers of central hydrophobic polypropylene and side hydrophilic polyethylene, is used clinically as a surfactant because of its amphiphilic characteristics. Poloxamer exists in the solution form at room temperature but transforms to a gel form at body temperature. Therefore, it provides a convenient and efficient means for forming a firm physical barrier during a laminectomy procedure36). Reigel et al.37) have demonstrated that poloxamer had an approximately 50% anti-adhesion effect in a rabbit laminectomy model. Furthermore, the gel that adhered to the tissue was hydrolyzed and, absorbed and was then excreted renally after several weeks50). Thus, the TSAA agent does not remain as a foreign body at the application site.

The TSAA agent, Guardix-SG® is easily applied to a laminectomy site after spinal surgery, it ensures complete coverage of the dura, and it localizes to the desired area due to its gel-forming capacity at body temperature. This experimental study assessed the efficacy of the TSAA agent in the prevention of postoperative adhesions in a rabbit laminectomy model. The findings of this study show that the TSAA agent appears to be useful as an interpositional physical barrier after laminectomy for the prevention or reduction of adhesions. Further experimental studies are needed to confirm its clinical value.