Efficacy and safety of a thermosensitive poloxamer-based hydrogel as an anti-adhesive agent in full-endoscopic spine surgery: a randomized controlled trial in Thailand

Article information

Asian Spine J. 2026;.asj.2025.0711

Publication date (electronic) : 2026 July 8

doi : https://doi.org/10.31616/asj.2025.0711

Vit Kotheeranurak^1,2, Nattapat Tangchitcharoen¹, Sompoom Sunpaweravong³, Surachat Jaroenwareekul¹, Worawat Limthongkul^1,2, Wicharn Yingsakmongkol^1,2, Jin-Sung Kim⁴, Weerasak Singhatanadgige^1,2

¹Department of Orthopaedics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand

²Center of Excellence in Biomechanics and Innovative Spine Surgery, Chulalongkorn University, Bangkok, Thailand

³Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

⁴Spine Center, Department of Neurosurgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

Corresponding author: Weerasak Singhatanadgige, King Chulalongkorn Memorial Hospital, 1873, Rama 4 Road, Pathumwan, Bangkok 10330, Thailand, Tel: +66-2-256-4000 (ext. 61208), Fax: +66-2-256-4000, E-mail: spinechula@gmail.com

Received 2025 November 13; Revised 2026 January 19; Accepted 2026 February 20.

Abstract

Introduction

Lumbar disc herniation (LDH) is a major cause of disability that can significantly impair patients’ quality of life and work capacity. Although both conservative and surgical treatments can be effective, surgery generally provides greater symptom relief and gains in quality-adjusted life years for patients with moderate to severe LDH [1]. Nevertheless, up to 30% of patients report persistent postoperative leg pain following lumbar discectomy [2,3].

Epidural fibrosis, defined as scar tissue formation encasing the dura and nerve roots at the surgical site, has been considered a key contributor to residual pain [4,5]. Several studies have demonstrated a correlation between the degree of fibrosis and the severity of postoperative back and leg pain [6–9]. Preventive strategies targeting the mechanisms of scar formation have therefore been developed [10]. Minimally invasive approaches, such as microdiscectomy, and adjuvant techniques, including low-dose radiation, have shown some benefit in reducing fibrotic adhesion [11]. Aside from such approaches, anti-adhesive biomaterials are also being explored. The ideal material should be biocompatible, be easily applied at the target site, and maintain a stable form long enough to inhibit fibrosis [4]. However, previous studies on anti-adhesive agents have reported variable results across surgical fields [4,10].

Poloxamer-based thermosensitive hydrogels represent a promising approach. These synthetic biomaterials undergo sol-to-gel transition at body temperature, enabling straightforward intraoperative delivery and persistence at the surgical site. One such formulation (Mediclore; CGBio Co. Ltd., Seongnam, Korea) that contains poloxamer, polyethylene glycol, and chitosan has demonstrated anti-adhesive efficacy in abdominal, gynecologic, and otolaryngologic surgery [12–17]. To date, however, evidence in lumbar spine surgery has been limited to animal models [18–20].

The present randomized controlled trial therefore aimed to evaluate the efficacy and safety of a thermosensitive poloxamer-based anti-adhesive hydrogel in patients undergoing full-endoscopic lumbar discectomy for LDH. Specifically, we investigated the effects of this hydrogel on postoperative leg pain, epidural fibrosis assessed via magnetic resonance imaging (MRI), and patient-reported quality-of-life outcomes.

Materials and Methods

Outcomes

Baseline demographic and clinical data, including age, sex, body mass index, preoperative diagnosis, physical examination findings, and radiographic results, were collected by a research assistant before surgery. Intraoperative variables, such as operative level, operative time, and complications, were also documented.

The primary outcome of this trial was the change in leg pain severity measured using the Visual Analog Scale (VAS-leg) 3 months after surgery. VAS-leg was selected as the primary endpoint given that radicular leg pain represents the most disabling symptom of LDH and reflects the clinical benefit most meaningful to patients after nerve-root decompression. Assessments were also performed before and 1, 3, 6, and 12 months after surgery.

Secondary outcomes included back pain intensity (VAS-back, 0–10) and disability measured using the ODI, 0–100 collected during the same follow-up visits. Additional outcomes included perioperative complications and postoperative MRI findings after 3 months to evaluate epidural fibrosis.

Postoperative fibrosis was assessed via MRI 3 months after surgery according to the epidural fibrosis grading method described by Ross et al. [21]. The surgical site was divided into five contiguous slices on axial images, with the third slice being the intervertebral disc of the operated level. Each image was then divided into four quadrants with the center of the neural foramen as the center point. The amount of fibrosis in each quadrant of each level was individually assessed. Fibrosis was graded on a scale of 0 to 4, with Grades 0 indicating no fibrosis and Grades 1, 2, 3, and 4 indicating fibrosis involving <25%, 25%–50%, 50%–75%, and >75% of the quadrant, respectively (Fig. 1). The highest grade was reported as an epidural scar, whereas Grades 3 and 4 indicated an extensive scar.

Fig. 1

Representative magnetic resonance imaging (MRI) images of epidural fibrosis graded according to the Ross classification. (A) Grade 1 epidural fibrosis. Axial T1-weighted MRI demonstrating minimal hypointense fibrotic tissue involving less than 25% of the epidural space (3A-1), with preservation of normal peridural fat signal. (B) Grade 2 epidural fibrosis. Axial T1-weighted MRI showing hypointense fibrotic tissue occupying approximately 25%–50% (4A-2) of the epidural space, with partial obscuration of peridural fat planes. (C, D) Grade 3 epidural fibrosis. (C) Axial T1-weighted MRI demonstrating hypointense fibrotic tissue involving approximately 50%–75% (3A-3 and 3C-3) of the epidural space, with marked loss of normal peridural fat planes. (D) Corresponding contrast-enhanced axial T1-weighted magnetic resonance image illustrating enhancement of epidural fibrotic tissue. (E) Grade 4 epidural fibrosis. Axial T1-weighted MRI demonstrating diffuse hypointense fibrotic tissue occupying more than 75% (3A-4) of the epidural space, with near-complete obliteration of peridural fat signal.

Although both epidural fibrosis and recurrent disc fragments may produce a mass effect, they can be differentiated by evaluating signal intensity, morphology, and their relationship to adjacent structures. Epidural fibrosis typically demonstrates increased signal intensity on early postcontrast T1-weighted sequences and appears as a curvilinear structure encasing the dural sac. This configuration reflects fibrous adhesions to the spinal canal and may create traction on the dura, causing displacement or distortion toward the scar. In contrast, recurrent disc herniation usually lacks enhancement on early postcontrast T1-weighted images and is characterized by a polypoid morphology protruding outward from the parent disc [7].

Sciatic nerve tension was assessed using the Straight Leg Raising (SLR) test, with the results being recorded as positive or negative. The test was performed before and 1 and 3 months after surgery. For the SLR test, the patient lay supine on the examination table with their knee fully extended while the examiner passively raised their leg. The test was considered positive if leg pain or radicular symptoms occurred before 70° of hip flexion. In positive cases, the exact angle of hip flexion at symptom onset was documented.

Results

A total of 82 patients were assessed for eligibility. Four patients were excluded, among whom two did not meet the inclusion criteria, one declined participation, and one had a documented allergy to crustaceans (a contraindication for the anti-adhesive material). A total of 78 patients were randomized at a 1:1 ratio (39 per group). Seven patients were excluded after randomization, among whom four were transferred to premium care, and three were lost to follow-up. Ultimately, data from 71 patients were available for analysis, forming the modified intention-to-treat population (Fig. 2). Baseline characteristics and intraoperative parameters are summarized in Table 1.

Fig. 2

CONSORT (Consolidated Standards of Reporting Trials) 2025 flow diagram of participants throughout the study.

Table 1

Demographic data

Patient-reported outcomes

Patient-reported outcomes are detailed in Table 2 and Fig. 3. VAS scores for leg pain, back pain, and numbness, as well as ODI scores, improved significantly from baseline at all follow-up visits (1, 3, 6, and 12 months; all p<0.0001 within groups), with no between-group differences having been observed at any timepoint. At 12 months, mean VAS-leg was 0.89 and 1.17 in the antiadhesive and control group, corresponding to mean reductions of −5.91 and −5.92 from baseline, respectively (p=0.995). Similar sustained improvements were observed for VAS-back and ODI scores, with no differences between the groups (Table 2).

Table 2

Patient-reported outcomes

Fig. 3

Line graphs showing patient-reported outcomes with standard error bars at baseline and 1, 3, 6, and 12 months after surgery. (A) Visual Analog Scale (VAS) back pain, (B) VAS leg pain, (C) leg numbness, and (D) Oswestry Disability Index (ODI). Blue dotted lines represent the control group; red solid lines represent the anti-adhesive group.

MRI outcomes

Out of the 71 patients analyzed, 48 patients (67.6%; 23 in the anti-adhesive group and 25 in the control group) underwent postoperative MRI at 3 months. Notably, 23 patients did not undergo MRI primarily due to personal refusal or inability to return for imaging due to nonmedical reasons. Baseline demographic and clinical characteristics were comparable between patients who did and did not undergo MRI. MRI findings are presented in Table 3. Accordingly, no significant differences in the prevalence of Grade 1 and 2 epidural fibrosis were observed between the groups. However, extensive fibrosis (Grades 3–4) occurred significantly less often in the anti-adhesive group than in the control group (8.7% vs. 32.0%, p=0.047).

Table 3

Result of epidural fibrosis from MRI at 3-month post-operation

Discussion

This randomized controlled trial showed that both groups exhibited significant improvements in patient-reported outcomes at 1, 3, 6, and 12 months after endoscopic lumbar discectomy. However, no between-group differences in leg pain, back pain, or disability scores were observed at any timepoint, and the magnitude of between-group differences remained well below established minimal clinically important difference thresholds [23]. These findings indicate that the addition of a thermosensitive anti-adhesive hydrogel did not confer clinically meaningful benefit in routine single-level endoscopic discectomy. However, the anti-adhesive group did exhibit a significantly lower incidence of extensive epidural fibrosis on MRI 3 months after surgery, reflecting a positive radiographic effect without the corresponding clinical benefits.

Various strategies have been explored to prevent epidural fibrosis and its potential contribution to postoperative symptoms. Unfortunately, the clinical effectiveness of such strategies has remained inconsistent. In human spine surgery, approaches such as suction drains, autologous fat grafts, and local steroid application have been shown to reduce epidural fibrosis on imaging and, in selected cohorts, may be associated with improved pain and functional outcomes [24,25]. However, these effects appear to vary according to surgical technique and patient-related factors. Other anti-adhesive materials have demonstrated mixed results. In particular, steroids and hyaluronic acid–based barriers offer only transient effects due to their short in vivo persistence, whereas ADCON-L gel, despite its early promise, was later found to be associated with adverse effects, such as delayed bone fusion and impaired muscle healing [26,27]. Thermosensitive poloxamer-based hydrogels have shown favorable anti-adhesive properties across different surgical specialties. For instance, Chung et al. [14] demonstrated reduced urethral stricture rates following transurethral resection of the prostate, while Choi et al. [15] reported improved postoperative shoulder mobility after axillary lymph node dissection in breast cancer patients. However, findings have not been uniformly positive. Indeed, Ahn et al. [12] found no significant improvements in swallowing function or cosmesis after thyroid surgery, while Kim et al. [13] reported reduced abdominal adhesions but no difference in adhesion-related symptoms after benign gynecologic surgery. Collectively, these mixed results suggest that the clinical efficacy of anti-adhesive agents is highly dependent on the surgical context and underlying pathology.

Evidence regarding thermosensitive anti-adhesive hydrogels in spine surgery has been largely confined to preclinical animal models. Shin et al. [19] demonstrated an approximately 50% reduction in adhesions after laminectomy in rabbits, while Park et al. [20] reported similar findings in another rabbit laminectomy model. Although these results are encouraging, they provide only radiographic and histologic validation. Translating these preclinical benefits into human clinical outcomes remains a key challenge and a principal motivation for the present randomized controlled trial.

Poloxamer, the active component of the investigated hydrogel, has been recognized by the US Food and Drug Administration as an inactive pharmaceutical excipient with a favorable safety profile [28]. Clinical studies in diverse surgical fields have reported no increase in complication rates when poloxamer-based agents were applied, supporting their biocompatibility and tolerability [12,15]. Although direct clinical data in human spine surgery remain limited, preclinical and translational studies on nerve and spinal cord regeneration, as well as other surgical settings, have consistently demonstrated acceptable safety outcomes. When formulated as a thermosensitive, poloxamer-based anti-adhesive hydrogel, the material exhibits biodegradable properties that allow it to transform into a gel at body temperature and maintain a temporary barrier effect before being resorbed, typically within approximately 2–4 weeks [18,19]. This resorption period is sufficient to cover the critical postoperative window of fibrotic adhesion formation [10], thereby providing a mechanistic rationale for its potential role in reducing epidural fibrosis after discectomy. Moreover, poloxamer-based hydrogels are biocompatible, well-tolerated, and, as demonstrated in our trial, did not cause any additional intraoperative or postoperative complications.

Despite the clear mechanistic basis for reducing fibrosis, the current study showed that both the intervention and control groups exhibited comparable clinical outcomes. This finding aligns with previous reports indicating that the presence or extent of epidural fibrosis does not consistently correlate with postoperative pain or functional limitation. Although Coskun et al. [29] observed significant differences in fibrosis grades on imaging, postoperative pain scores did not correspond to these radiological findings, suggesting that fibrosis may be an imaging marker rather than a direct cause of pain. Similarly, Annertz et al. [30] found no differences in the prevalence or size of epidural fibrosis between symptomatic and asymptomatic patients. They note that six of the eight patients who underwent reoperation for persistent sciatica continued to experience symptoms despite surgical removal of the fibrotic tissue. Taken together, these studies and the present findings indicate that although thermosensitive hydrogels can reduce the radiographic burden of scar formation, such reductions do not necessarily translate into clinically meaningful improvements following routine single-level endoscopic discectomy.

This study has several limitations. First, the follow-up period was limited to 12 months, which is adequate for assessing pain and disability but may be too short to evaluate long-term recurrence or reoperation rates associated with epidural fibrosis. Second, not all participants underwent postoperative MRI, primarily due to personal refusal or logistical barriers, which may have modestly reduced the statistical power for our radiographic analysis. Third, the use of methylprednisolone as the control intervention constitutes an additional consideration. Corticosteroids possess well-established anti-inflammatory and antifibrotic properties and have been commonly administered during lumbar discectomy to reduce postoperative nerve-root irritation [31]. As such, methylprednisolone likely functioned as an active comparator, potentially attenuating between-group differences and reducing the observable effect size of the anti-adhesive hydrogel. Fourth, all procedures were performed using the uniportal interlaminar endoscopic approach, which inherently minimizes soft tissue trauma. This low baseline tissue disruption may have created a ceiling effect, limiting the measurable clinical benefit of additional anti-adhesive intervention. Moreover, although fibrosis reduction may not provide tangible benefits in routine single-level discectomy, it could hold greater clinical relevance in revision or multilevel surgeries wherein postoperative adhesions are a well-recognized cause of technical difficulty and recurrent symptoms. Finally, the single-center design and modest sample size may limit the generalizability of our findings to broader or higher-risk populations. Although the single-surgeon design enhanced procedural consistency and minimized technical variability, it may limit the generalizability of our findings to surgeons with different levels of experience or those at varying stages of the endoscopic learning curve. Future multicenter studies with longer follow-up and standardized fibrosis grading protocols are warranted to validate these findings and determine the clinical contexts in which anti-adhesive materials offer the greatest value.

Conclusions

This randomized controlled trial revealed that the thermosensitive poloxamer-based anti-adhesive hydrogel did not promote greater improvements in the primary outcome (i.e., leg pain) than did the control condition, as both groups achieved similar and clinically meaningful recovery following full-endoscopic lumbar discectomy. However, the hydrogel significantly reduced the incidence of extensive epidural fibrosis on MRI 3 months after surgery, indicating a clear radiographic benefit without added risk or complications. These findings suggest that although fibrosis reduction may not enhance outcomes in standard single-level procedures, such materials could have greater relevance in revision or multilevel surgeries where postoperative adhesions are more likely to affect recovery and reoperation risk.

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