Experimental and Clinical Evaluation of Spongostan as a Substitute for Spongel in Sellar Floor Reconstruction during Endoscopic Transsphenoidal Surgery

Abstract

Absorbable gelatin sponges are widely used as hemostatic and reconstructive materials in neurosurgery. Global discontinuation of Gelfoam and withdrawal of Spongel from the Japanese market have created an urgent need for alternatives. This study was performed to evaluate the utility of Spongostan as a substitute for Spongel and Gelfoam in sellar floor reconstruction using the fibrin glue-soaked gelatin sponge method.

Two gelatin sponges (Spongel and Spongostan) and 2 fibrin sealants (Beriplast and Bolheal) were combined to prepare 4 fibrin glue-soaked gelatin sponge combinations. Adhesive strength was measured using a tensile strength test according to ASTM F2458-05 and analyzed using 2-way analysis of variance. A retrospective review was also conducted for patients who underwent endoscopic transsphenoidal surgery for pituitary adenoma between May 2024 and October 2025, in which fibrin glue-soaked gelatin sponge prepared with Spongostan was used for sellar floor reconstruction.

Spongostan showed significantly higher adhesive strength than Spongel (F(1,20) = 13.72, p = 0.0014), whereas neither the fibrin sealant type nor the sponge-fibrin sealant interaction was significant (both p = 0.73). In 11 clinical cases (mean age 66 ± 16 years), intraoperative cerebrospinal fluid leakage occurred in 5 cases and postoperative leakage in one case, in a patient who had undergone prior radiotherapy. No hemorrhage, meningitis, or material-related complications occurred. These findings suggest that Spongostan may serve as a feasible alternative to Spongel for fibrin glue-soaked gelatin sponge-based sellar floor reconstruction during endoscopic transsphenoidal surgery.

Introduction

Absorbable gelatin sponges (Spongel, Gelfoam, and Spongostan) are widely used as topical hemostatic materials in neurosurgical procedures.¹⁾ In addition to their hemostatic role, gelatin sponges are also used in endoscopic endonasal skull base surgery to prevent cerebrospinal fluid (CSF) leakage and reinforce dural repair.^2-5) The fibrin glue-soaked gelatin sponge (FGGS) method is useful for sellar floor reconstruction, providing secure fixation and watertight sealing of the reconstructed area.⁴⁾ However, Gelfoam has recently been discontinued worldwide, and Spongel has been withdrawn from the Japanese market, making the selection of alternative materials an urgent concern for neurosurgeons in Japan. The aim of this study is to examine the usefulness of Spongostan as a substitute for Spongel and Gelfoam in sellar floor reconstruction. The adhesive strengths of Spongel and Spongostan were compared using the FGGS method, and clinical cases in which Spongostan was used for sellar floor reconstruction during transsphenoidal surgery were reviewed.

Materials and Methods

Experimental evaluation of adhesive strength using the FGGS method

The adhesive strength of FGGS was evaluated in accordance with the Standard Test Method for Wound Closure Strength of Tissue Adhesives and Sealants, ASTM F2458-05 (Reapproved 2024).⁶⁾ Two types of gelatin sponges (Spongel, LTL Pharma, Tokyo, Japan; and Spongostan, Ethicon, Johnson & Johnson, Raritan, NJ, USA) and 2 commercially available fibrin sealants (Beriplast P Combi-Set, CSL Behring K.K., Tokyo, Japan; and Bolheal, Meiji Seika Pharma, Tokyo, Japan) were used to prepare 4 FGGS combinations. Thrombin was diluted with normal saline at a ratio of 1:10, following the protocol described by Campos et al.,⁴⁾ which provides the highest adhesive performance. After the fibrinogen component was applied to the gelatin sponge (1 × 3 cm, 3 mm thickness), the diluted thrombin solution was added, and the mixture was incubated for 20 s to allow polymerization. To ensure reproducibility, FGGS preparation was performed according to a strictly standardized protocol. The size and thickness of the gelatin sponge, concentrations of fibrinogen and thrombin, order of application, incubation time, and compression conditions were kept identical across all trials. All FGGS specimens were prepared by the same investigator to minimize procedural variability. For evaluation of adhesive strength, defatted frozen porcine skin was used, with the dermal side serving as the test substrate. After thawing and rehydrating at room temperature, one skin sheet was mounted on a fixed jig plate and the other on a sliding jig plate, both secured with metal clips (Figure 1). The FGGS was placed at the junction between the 2 skin surfaces, and a 123-g weight was applied for 3 min to ensure uniform adhesion. A tensile strength test was performed using a universal testing machine (EZ-Test, Shimadzu Corp., Kyoto, Japan) at a crosshead speed of 50 mm/min. The maximum tensile load (N) was recorded as adhesive strength. Six independent trials were conducted for each condition, and the mean ± standard deviation was calculated. The sample size (n=6 per condition) was selected in accordance with a previous study⁴⁾ and the exploratory nature of the present work. The study was designed to characterize relative adhesive performance under standardized conditions rather than to establish definitive thresholds. Two-way analysis of variance (ANOVA) was performed with gelatin sponge type (Spongel vs. Spongostan) and fibrin sealant type (Beriplast vs. Bolheal) as fixed effects, and their interaction was included in the model. A p < 0.05 was considered significant. Statistical analyses were conducted using R (ver. 4.4.2; R Foundation for Statistical Computing, Vienna, Austria).

Figure 1.

Experimental setup for the tensile strength test. Two sheets of defatted frozen porcine skin were placed in contact, with one mounted on a fixed jig plate and the other on a sliding jig plate connected to the testing apparatus. The skin sheets were secured with metal clips. An FGGS was placed onto the junction between the two skin surfaces, and a 123-g weight was applied for 3 min to ensure adhesion. Tensile load was then applied at a constant crosshead speed of 50 mm/min using a universal testing machine (EZ-Test, Shimadzu Corp., Kyoto, Japan), and the maximum tensile load (N) was recorded as the adhesive strength.

FGGS: fibrin glue-soaked gelatin sponge

Clinical evaluation of Spongostan in endoscopic transsphenoidal surgery

A retrospective clinical study was conducted to evaluate the efficacy and safety of the FGGS method using Spongostan during endoscopic transsphenoidal surgery (TSS) for pituitary adenoma (pituitary neuroendocrine tumor; PitNET). The subjects were patients who underwent TSS at Yamaguchi University Hospital between May 2024 and October 2025 and received Spongostan for sellar floor reconstruction. For Esposito Grade 0-2 intraoperative CSF leakage, closure was achieved using FGGS prepared with Spongostan. After tumor removal, the arachnoid (diaphragmatic) defect and any visible CSF leakage were gently suctioned dry, and FGGS was applied to cover the defect. The resection cavity within the sella was then filled with FGGS. Subsequently, the dural edges were sutured with one or 2 stitches for primary closure, followed by rigid reconstruction using nasal septal bone, and the sellar floor was covered with 2-3 additional FGGS pieces. The incidence of postoperative CSF leakage, hemorrhage, and other complications was retrospectively assessed.

In Japan, Spongostan does not have an indication for neurosurgery (approved only for postoperative hemostasis for anorectal procedures); therefore, the off-label use of Spongostan^Ⓡ was approved through the hospital's novel medical practice review process (off-label use review), and written informed consent was obtained from each patient prior to its clinical use. Patients were informed of the off-label nature of the material, potential risks associated with the Spongostan, including nerve compression due to material expansion in a confined space, infection or abscess formation, and rare allergic reactions to porcine-derived gelatin, as well as alternative reconstruction methods (such as autologous fat graft, nasoseptal flap, fascia lata, or collagen-based dural substitutes) prior to surgery. The retrospective chart review was approved by the Institutional Review Board of Yamaguchi University Hospital (approval no. H2021-047-5), and the requirement for informed consent was waived due to the retrospective nature of the study.

Results

Experimental evaluation

Four FGGS combinations were tested. Load-displacement curves obtained from the tensile strength tests are shown in Figure 2. The mean adhesive strength (N, mean ± standard deviation) was 0.316 ± 0.054 for Spongel/Bolheal, 0.268 ± 0.058 for Spongel/Beriplast, 0.546 ± 0.228 for Spongostan/Bolheal, and 0.545 ± 0.232 for Spongostan/Beriplast. A 2-way ANOVA revealed a significant main effect for gelatin sponge type (F(1,20)=13.72, p = 0.0014), but no significant main effect of fibrin sealant or the sponge-fibrin sealant interaction (both p = 0.73; Table 1). The results of the interaction analysis are illustrated in Figure 3. These data show that adhesive strength was primarily determined by the intrinsic properties of the gelatin sponge, rather than by the type of fibrin sealant.

Figure 2.

Load-displacement curves obtained from tensile strength tests using the FGGS method. (A) All load-displacement curves from tensile tests performed using Bolheal as the fibrin sealant. (B) All load-displacement curves from tensile tests performed using Beriplast. In each panel, curves obtained with Spongostan are shown in black, and those obtained with Spongel are shown in gray. The vertical axis represents tensile load (N) applied in the test, and the horizontal axis represents displacement (mm). The maximum tensile load recorded during each test was defined as the adhesive strength.

FGGS: fibrin glue-soaked gelatin sponge

Table 1.

Summary of 2-Way ANOVA for Adhesive Strength of FGGS Specimens

Effect	df	Sum Sq	Mean Sq	F value	p
gelatin sponge	1.0	0.384	0.384	13.7	0.001
fibrin sealant	1.0	0.003	0.003	0.1	0.728
gelatin sponge × fibrin sealant	1.0	0.003	0.003	0.1	0.734
Residuals	20.0	0.560	0.028

Two-way analysis of variance was performed to evaluate the effects of gelatin sponge type (Spongel vs. Spongostan) and fibrin sealant type (Beriplast vs. Bolheal) on adhesive strength. A significant main effect was found for the gelatin sponge factor (F(1,20) = 13.72, p = 0.0014), indicating that Spongostan has significantly higher adhesive strength than Spongel. Neither the fibrin sealant factor nor the interaction between the two factors was significant (both p = 0.73).

ANOVA: analysis of variance; df: degrees of freedom; Mean Sq: mean square; Sum Sq: sum of squares

Figure 3.

Interaction plot of adhesive strength analyzed by 2-way ANOVA. The horizontal axis indicates the type of gelatin sponge (Spongostan and Spongel), and the vertical axis represents adhesive strength (N). Each point represents the mean adhesive strength from six independent trials, and error bars denote the SEM, indicating the precision of the estimated group means. Lines represent the type of fibrin sealant: red for Bolheal and black for Beriplast. The nearly parallel profiles of the 2 lines indicate no significant interaction between the gelatin sponge and fibrin sealant, whereas Spongostan exhibited a consistently higher adhesive strength than Spongel (P= 0.0014).

ANOVA: analysis of variance; SEM: standard error of the mean

Clinical evaluation

A total of 11 patients (6 men, 5 women; mean age, 66 ± 16 years) with macroadenomas were included in the study. Intraoperative CSF leakage occurred in 5 cases (45.5%; Esposito Grade 1: 3 cases, grade 2: 2 cases). Five other cases had an Esposito Grade of 0. FGGS prepared with Spongostan had satisfactory handling characteristics and secure adhesion without the use of additional packing materials. No intraoperative detachment or displacement was observed. Postoperatively, CSF leakage occurred in only 1 case: a patient who had undergone stereotactic radiotherapy (21 Gy / 3 fractions) 15 years earlier and had grade 2 intraoperative leakage. No other cases showed CSF leakage. There was no postoperative hemorrhage, meningitis, allergic reactions, or other complications. The mean follow-up period was 7.7 ± 4.2 months.

Discussion

This study showed that Spongostan exhibited significantly greater adhesive strength than Spongel when evaluated using the FGGS method.⁴⁾ There was no significant difference between the 2 fibrin sealants, indicating that the intrinsic physical properties of the gelatin sponge itself, rather than the type of fibrin sealants, determine adhesive performance. The absence of an interaction effect further suggests that no synergistic or antagonistic effect arises from specific sponge-fibrin sealant combinations. From a clinical perspective, these findings suggest that Spongostan may represent a feasible option for FGGS-based sellar floor reconstruction in selected cases.

Although the precise mechanisms underlying the greater adhesive strength of Spongostan remain unclear, several plausible hypotheses may explain this observation. Based on our operative experience, Spongostan appears to be more compressible and pliable, resembling Gelfoam, whereas Spongel tends to be denser and less deformable. Such differences in handling characteristics may reflect variations in porosity and elastic behavior, which could influence fibrin penetration, retention within the sponge matrix, and mechanical interlocking at the tissue-sponge interface. In addition, the greater variability in maximum tensile load observed for Spongostan may reflect heterogeneity in sponge microstructure or fibrin distribution. Importantly, these hypotheses are speculative and are derived from subjective intraoperative handling experience, rather than from objective material characterization or quantitative analysis. Objective evaluation of material properties was not feasible because Spongel has been discontinued and is difficult to obtain as a comparative material. Given the current supply status of Spongel, similar objective validation will remain difficult. This limitation should be considered when interpreting the findings and their generalizability.

One case of postoperative CSF leakage occurred following reoperation in a patient with prior radiotherapy. Repeat TSS after radiotherapy has been reported as a risk factor for CSF leakage,⁷⁾ likely due to impaired tissue healing and altered vascularity. Therefore, in patients with prior radiotherapy or other high-risk features, multilayer reconstruction using autologous fat grafts and/or a vascularized nasoseptal flap may be more appropriate than FGGS-based reconstruction alone. While the present clinical observations generally support the experimental findings, direct extrapolation from an in vitro adhesive test to in vivo performance should be approached with caution, as factors such as tissue moisture, CSF pulsation, and postoperative inflammatory responses can significantly influence adhesion and healing.

Collagen-based dural substitutes such as DuraGen have been widely used for skull base reconstruction in cases with high-flow CSF leakage.⁸⁾ In contrast, FGGS-based reconstruction using gelatin sponges is generally applied for small to moderate CSF leakage or as an adjunct to multilayer reconstruction techniques.^4,8,9) From this perspective, Spongostan should be regarded not as a replacement for established dural substitutes, but as a complementary option. In addition, cost considerations differ between gelatin sponges and collagen-based dural substitutes, and prices may vary across countries and healthcare systems.

Beyond the specific comparison of gelatin sponge materials, the present study has broader implications in the context of medical material availability in Japan. Recent discontinuation and supply constraints of commonly used surgical materials have demonstrated the vulnerability of clinical practice to changes in manufacturing and distribution. In such circumstances, systematic evaluation of alternative materials becomes increasingly important to maintain the continuity and safety of standard surgical procedures. From this perspective, the present work provides an example of how existing, clinically available materials can be reassessed and positioned as potential substitutes based on objective experimental data and carefully interpreted clinical observations, rather than empirical substitution alone.

This study has several limitations. First, Spongostan is not approved for skull base reconstruction in Japan, and its clinical use in this cohort constituted an off-label application conducted under institutional oversight with appropriate informed consent. Therefore, the findings require further validation before any consideration of broader clinical application. Second, this study evaluated adhesive strength, but did not assess hemostatic efficacy. Third, Gelfoam, which has been widely used and reported in prior literature,⁴⁾ was unavailable in our setting, precluding direct comparison with Spongostan or Spongel. Fourth, the experimental component was designed as an exploratory analysis under standardized conditions, and the small clinical sample size and single-center retrospective design limit generalizability.

In conclusion, Spongostan demonstrated superior adhesive strength compared with Spongel under standardized experimental conditions. Although clinical conclusions must be interpreted cautiously, the present findings suggest that Spongostan may serve as a practical and feasible alternative to Spongel for FGGS-based sellar floor reconstruction during endoscopic TSS.

Disclaimer

Author Hideyuki Ishihara is one of the Editorial Board members of the Journal. This author was not involved in the peer-review or decision-making process for this paper.

Conflicts of Interest Disclosure

All authors have no conflict of interest.