2025 Volume 12 Pages 477-482
DuraGen, a collagen matrix-based artificial dura mater, is widely used in neurosurgery because of its biocompatibility and ease of use. Although generally considered safe, we present a rare case of a foreign body reaction to DuraGen presenting as a sterile inflammatory response. A 40-year-old woman underwent total resection of a right convexity meningioma, with dural repair using DuraGen. On postoperative day 31, she developed headache, nausea, and vomiting. Imaging revealed significant cerebral edema around the surgical cavity with midline shift but no signs of infection on diffusion-weighted imaging. To rule out infection, reoperation was performed. Intraoperatively, there was no purulence or necrosis, but DuraGen was found adherent to the cortical surface. The artificial dura was removed and replaced with Gore-Tex. Microbiological cultures were negative. Histopathology showed inflammatory granulation tissue with eosinophilic infiltration, indicating a foreign body reaction. The patient's symptoms resolved immediately after surgery, and follow-up imaging at 5 months confirmed complete radiological resolution. This case highlights a rare but significant complication of DuraGen, demonstrating that foreign body reactions can mimic infectious processes and lead to severe cerebral edema and intracranial hypertension. Awareness of this potential complication is important for neurosurgeons, especially when infection is suspected but not clearly supported by imaging or intraoperative findings. Timely recognition and removal of the offending material can lead to rapid clinical and radiological improvement. This case underscores the importance of considering foreign body reaction in the differential diagnosis of delayed deterioration after duraplasty, particularly when infection is not definitively confirmed.
Dural defect repair is a common procedure in neurosurgery after various interventions such as tumor resection, decompressive craniectomy, and trauma management. Traditionally, autologous tissues such as fascia lata have been used for dural reconstruction. However, artificial dura mater substitutes have gained popularity because of their availability, standardized quality, and ability to reduce operative time.
DuraGen, a collagen matrix-based artificial dura mater derived from bovine Achilles tendon, has been widely adopted for neurosurgical applications. Its porous structure allows fibroblast infiltration and neovascularization, promoting natural dural regeneration while providing a watertight barrier to prevent cerebrospinal fluid leakage.1,2) Studies have demonstrated its success in cerebrospinal fluid containment in over 95% of cases, with the material allowing sutureless application.3)
Foreign body reactions are complex immune responses to implanted biomaterials characterized by protein adsorption, acute and chronic inflammation, foreign body giant cell formation, and fibrous encapsulation.4,5) Although DuraGen undergoes viral inactivation processing and is designed to minimize immunogenicity, rare cases of adverse reactions have been documented with various dural substitutes.6)
When such reactions occur, they may present with symptoms including headache, neurological deficits, or signs of intracranial hypertension. Recent studies have also noted concerning findings such as meningioma cell invasion into DuraGen-derived dura mater.7)
We report a rare case of sterile inflammatory response with intracranial hypertension caused by a foreign body reaction to DuraGen, which was successfully treated by removal of the material and alternative dural reconstruction, aiming to highlight diagnostic and therapeutic considerations in post-duraplasty complications.
A 40-year-old woman without significant medical history was incidentally found to have a right convexity meningioma on a head computed tomography performed during a dental procedure. Serial imaging revealed gradual growth of the tumor (Fig. 1A and B). Preoperative fluid-attenuated inversion recovery (FLAIR) imaging revealed no peritumoral edema (Fig. 1C), indicating a well-circumscribed lesion without surrounding pial disruption. The patient underwent craniotomy for tumor resection, achieving Simpson grade I total removal. The dural defect was repaired using DuraGen, and the immediate postoperative course was uneventful, except for minor surgical site pain. Postoperative magnetic resonance imaging (MRI) confirmed complete tumor resection with no complications (Fig. 1D and E).
Preoperative and immediate postoperative MRI findings. (A) T1-weighted MRI with gadolinium 2 years before surgery showing the initial meningioma. (B) T1-weighted MRI with gadolinium at admission showing tumor growth. (C) Preoperative FLAIR imaging showing the meningioma without peritumoral edema; no high signal intensity is observed in the surrounding brain parenchyma. (D) Immediate postoperative T1-weighted MRI with gadolinium confirming complete tumor resection. (E) Immediate postoperative FLAIR imaging showing no high signal intensity in the brain parenchyma.
FLAIR: fluid-attenuated inversion recovery; MRI: magnetic resonance imaging
A total of 31 days after surgery, the patient presented to the emergency department with sudden onset of headache, nausea, and vomiting. On examination, she was drowsy but arousable (Glasgow coma scale E3V5M6), without focal neurological deficits. Notably, there was no evidence of fever, erythema, swelling, or tenderness at the surgical site.
Computed tomography revealed significant cerebral edema around the surgical cavity with midline shift (Fig. 2A). T1-weighted images with gadolinium showed enhancement of the capsule surrounding the artificial dura (Fig. 2B). Diffusion-weighted imaging demonstrated partial high signal intensity in the epidural region but not the typical pattern seen in pyogenic abscesses (Fig. 2C). FLAIR imaging showed extensive high signal intensity in the surrounding brain parenchyma (Fig. 2D).
Radiological findings at symptom onset (31 days post-surgery). (A) CT scan showing cerebral edema around the surgical cavity. (B) T1-weighted MRI with gadolinium demonstrating thickening and enhancement of DuraGen (white arrows). (C) Diffusion-weighted imaging showing high signal intensity only in the epidural space, not typical of pyogenic abscess. (D) FLAIR imaging revealing extensive high signal intensity in the surrounding brain parenchyma. (E) FLAIR imaging 5 months after DuraGen removal showing complete resolution of parenchymal high signal intensity.
CT: computed tomography; FLAIR: fluid-attenuated inversion recovery; MRI: magnetic resonance imaging
Considering the clinical and radiological findings, infectious abscess and foreign body reaction were considered in the differential diagnosis. Despite the absence of typical infection signs, such as wound erythema or fever, we proceeded with reoperation to remove the bone flap and DuraGen, initially planning to reconstruct the dura with fascia lata.
During the second operation, examination of the retracted scalp and surgical site revealed no evidence of erythema, swelling, or other signs of infection (Fig. 3A). After removing the bone flap, the onlay DuraGen was clearly visible and could be easily removed (Fig. 3B). However, the inlay DuraGen was noted to be firmly adherent to the brain surface, with granulation tissue formation, requiring careful dissection to reduce the mass effect without causing additional brain injury (Fig. 3C). There was no evidence of infection, such as purulence, malodor, or discoloration of tissues. Complete removal of the DuraGen was achieved, followed by dural reconstruction using Gore-Tex synthetic dura mater. The autologous bone flap was then replaced. Antibiotics were administered for only 3 days postoperatively. Intraoperatively, there was no clear difference in the degree of adhesion across different regions; rather, DuraGen exhibited uniformly strong adhesion to the cortical surface throughout the contact area. In the initial tumor resection, adhesion between the tumor and brain surface was observed only at the central (deepest) portion, where the arachnoid membrane was likely absent, potentially contributing to direct contact between DuraGen and brain cortex, which may have played a role in the subsequent inflammatory response.
Surgical findings during DuraGen removal. (A) Retracted scalp and surgical site showing no evidence of erythema, swelling, or other signs of infection. (B) After bone flap removal, the onlay DuraGen was clearly visible and easily removed. (C) The inlay DuraGen was found adherent to the brain surface with granulation tissue formation, requiring careful dissection to reduce mass effect.
All microbiological cultures from the surgical specimens returned negative for bacterial growth. Histopathological examination revealed inflammatory granulation tissue with marked eosinophilic and lymphocytic infiltration around the artificial dura, consistent with a foreign body reaction rather than bacterial infection (Fig. 4A-D).
Histopathological findings of the removed DuraGen material. (A) Low-power view showing inflammatory granulation tissue with dense cellularity (H&E stain, scale bar = 500 μm). (B) High-power view revealing prominent infiltration of eosinophils within the granulation tissue (H&E stain, scale bar = 50 μm). (C) Inflammatory cell infiltration surrounding the artificial dura mater (H&E stain, scale bar = 100 μm). (D) Lymphocyte-predominant inflammatory infiltrate within the fibrous matrix (H&E stain, scale bar = 100 μm).
H&E: hematoxylin and eosin
After the second surgery, the patient's symptoms of intracranial hypertension resolved promptly. Postoperative MRI showed resolution of the midline shift, and follow-up MRI at 5 months revealed complete resolution of the high-intensity signals on FLAIR imaging (Fig. 2E). Based on these findings, we diagnosed the condition as a sterile inflammatory response caused by a foreign body reaction to DuraGen.
DuraGen is composed of type I collagen derived from bovine Achilles tendon, processed to remove cellular components while preserving the collagen matrix structure. It undergoes viral inactivation treatment and is designed to minimize immunogenicity.1) Its porous architecture facilitates fibroblast infiltration and neovascularization, promoting tissue integration and dural regeneration.2) Although generally well-tolerated, DuraGen can occasionally induce a significant foreign body reaction, as demonstrated in our case.
The pathophysiology of foreign body reactions involves several phases: protein adsorption to the biomaterial surface, acute inflammation with neutrophil recruitment, chronic inflammation characterized by monocytes/macrophages, foreign body giant cell formation, and finally, fibrous encapsulation.4,8) In our case, histopathological findings of eosinophilic infiltration strongly suggest an allergic or hypersensitivity component to the reaction.
Differentiating between foreign body reactions and infections can be challenging in the postoperative period. In our case, several features-including radiological findings, intraoperative observations, and histopathology-supported a diagnosis of foreign body reaction rather than infection: the absence of typical infectious signs clinically, the pattern of signal abnormality on diffusion-weighted imaging, negative bacterial cultures, histopathological evidence of eosinophilic infiltration, and the rapid resolution of symptoms after DuraGen removal with minimal antibiotic therapy.
Imaging plays a crucial role in diagnosing foreign body reactions. MRI typically shows abnormal enhancement and surrounding edema, which can mimic tumor recurrence or infection. In our patient, the extensive cerebral edema and midline shift without typical diffusion restriction patterns of pyogenic abscess were key findings suggesting a foreign body reaction.
The treatment strategies for foreign body reactions to dural substitutes depend on the severity of symptoms. Mild cases may be managed conservatively with anti-inflammatory medications and steroids. However, in cases with significant mass effect or intracranial hypertension, as in our patient, surgical removal of the material is indicated. Our case demonstrates that prompt removal of the reactive material and replacement with an alternative dural substitute can result in a rapid resolution of symptoms.
Foreign body reactions in the brain generally follow the classical cascade seen in peripheral tissues-beginning with protein adsorption on the biomaterial surface, progressing through acute and chronic inflammation, and culminating in fibrous encapsulation.4,5,8) However, in the central nervous system, this process may be amplified by blood-brain barrier disruption, loss of arachnoid protection, and localized neuroinflammation, making the response more clinically significant. A collagen-based implant such as DuraGen, despite being processed to reduce immunogenicity, can trigger this cascade in susceptible individuals. Factors influencing this include the degree of direct cortical contact, contamination with blood products, and the patient's immunological predisposition. Our histopathological findings-marked eosinophilic and lymphocytic infiltration-are consistent with these mechanisms, suggesting a helper T cell-skewed immune response possibly linked to delayed-type hypersensitivity.
In rare instances, foreign body reactions to DuraGen have been reported, although most did not result in abscess formation. For example, Tamura et al.7) reported meningioma cell invasion into DuraGen-derived dura mater accompanied by inflammation but without abscess formation. To the best of our knowledge, only a few reports describe abscess-like or sterile inflammatory presentations because of artificial dural substitutes.6,9) Sapkota and Karn documented an extradural abscess after synthetic fabric duraplasty, indicating that collagen-based and non-collagenous materials can occasionally provoke sterile inflammatory responses.10) In most of these cases, the pathological findings included chronic inflammation, fibrous granulation, and eosinophilic or lymphocytic infiltrates, which were consistent with our own findings.
When faced with similar clinical scenarios, surgeons should consider rapid intraoperative assessment techniques, such as Gram staining and frozen section pathological examination, to differentiate between infection and foreign body reaction. This distinction has important implications for postoperative management, particularly, regarding the duration of antibiotic therapy. Moreover, strategies to minimize the risk of foreign body reaction should be considered when using collagen-based dural substitutes, such as DuraGen. These may include thorough intraoperative irrigation to reduce residual blood or proteinaceous debris that may potentiate inflammation and careful placement to avoid direct cortical contact when not necessary. Although routine prophylactic removal is not currently recommended, in cases where unexplained postoperative symptoms arise, early suspicion and prompt intervention are warranted. Awareness and preparedness for such rare complications can significantly improve patient outcomes and inform future material selection in dural reconstruction.
Written informed consent was obtained from the patient for publication of this case report and accompanying images.
This case highlights the potential for DuraGen to cause a foreign body reaction manifesting as a sterile inflammatory response with intracranial hypertension. Although rare, neurosurgeons should be aware of this potential complication and include it in the differential diagnosis when patients present with neurological deterioration after dural repair with DuraGen, particularly when infection indicators are equivocal. Careful radiological evaluation, clinical assessment, and, when necessary, surgical exploration are essential for establishing the correct diagnosis. Prompt removal of the artificial dura mater and alternative dural reconstruction provides definitive treatment in severe cases. Our experience suggests that even materials designed to minimize immunogenicity, such as DuraGen, can occasionally trigger significant foreign body reactions in susceptible individuals.
All authors have no conflict of interest. All authors are members of The Japan Neurosurgical Society (JNS) have completed the Self-reported Conflict of Interest Disclosure Statement Forms available at the website for JNS members.
