A Unique Approach to Neurosurgical Wound Closure With Porcine Urinary Bladder Matrix: An Illustrative Case Series

PUBM is a xenograft used for surgical reinforcement and management of soft tissue wounds and burns. It is composed of an ECM derived from the inner 2 layers of the porcine urinary bladder, specifically, the epithelial and lamina propria layers.¹ This completely resorbable xenograft accelerates wound healing by facilitating constructive remodeling. The xenograft seems to have antimicrobial properties; however, studies have shown that the antibacterial activity is not due to the ECM itself but instead results from its degradation products.² This includes activity against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. 

Once the ECM is implanted, it initiates recruitment of white blood cells as well as fibroblasts into the scaffold to facilitate constructive remodeling. Fibroblasts deposit collagen to increase the strength and integrity of the tissue, and neovascularization occurs through endothelial growth factors including VEGF. Host tissue at the site of the reconstruction receives signals from the ECM to stimulate an adaptive response. The matrix is ultimately reabsorbed into the tissue, thus requiring no extraction or removal process after healing has been achieved. In this report, 2 cases of neurosurgical wounds successfully managed with PUBM are described.

Written informed consent was obtained on admission, and all material presented in this report has been deidentified. Institutional Review Board approval was exempt for this report.

Case 1

A 23-year-old White female presented with a past medical history of achondroplasia, body mass index of 31.89 kg/m², and no history of smoking or current alcohol use. Neurologically, the patient was fully oriented, and level of consciousness was appropriate for age. Cranial nerves were II-XII intact, motor strength was decreased in the legs, sensation was decreased in the lower extremities, and speech was normal. There were no active home medications that would have interfered with wound healing and no electrolyte abnormalities were noted. This patient initially underwent laminectomy for a World Health Organization grade I ependymoma extending from T10-S1 vertebral levels. After initial laminectomy, the patient was returned to the OR by the neurosurgical team 19 days after the index operation for a wound infection and high output CSF fistula. At that time, the wound measured 27 cm × 3.1cm × 7.2 cm. 

The patient was taken to the OR for wound debridement and implantation of PUBM 3 days after surgical wound care consultation (ie, 29 days after initial wound complications were documented; Figure 1A). Examination of the wound revealed areas of fat necrosis, fibrinous exudate, and dermal dehiscence. The resulting wound post debridement in the OR measured 22 cm in length with a maximum width of 4 cm; the depth measured 2 cm cephalad and progressed to a maximum depth of 6.5 cm near the caudad portion of the wound. Clear fluid was emanating from the caudad area, consistent with a CSF fistula (Figure 1A). The patient was seen to have drainage from the lower aspect of the incision. Fluid collections for beta-2 transferrin were sent. After surgical debridement, a reasonable bed of granulation tissue or viable subcutaneous tissue remained. The implantation began with 500 mg of PUBM in particulate form, which comprised a single layer of PUBM that was lyophilized and ground to a fine powder. A 3-layer PUBM wound sheet measuring 10 cm × 15 cm was hydrated, cut into strips, and implanted over the powder. A strip of this 3-layer sheet was also packed in the CSF fistula tract. The skin edges were somewhat scalloped from previous pull-through of suture material, raising concern for dermal ischemia. No sutures were used in the dermal closure because of this concern. The skin edges were opposed with strips of adhesive tape used for primary wound closure. The open wound was approximated with a NPWT drape. The drape was left in place until progress on the wound and drainage were noted; there was no set duration for the drape to remain. There was no periwound erythema but moderate amounts of drainage owing to xenograft implantation were noted. Blood cultures prior to surgery were clean with no growth for 5 days. The patient was given intravenous antibiotics for 1 day until transition to oral cephalexin until discharge on postoperative day 6 status post-surgical debridement of the wound on the back and implantation of the PUBM sheet. The patient was not diagnosed with sepsis or septic shock throughout the operative course. It was suspected that a contributing factor to the wound was pressure related. Therefore, an electric air fluidized therapy bed and patient instruction to offload the midback area was strongly recommended. At 12 days post application of PUBM, the wound had closed (Figure 1B, C).

Case 2

A 76-year-old Hispanic female with poorly controlled type 2 diabetes, hypertension, and hypothyroidism underwent an open posterior spinal fixation and instrumented fusion of C5-T5 vertebral levels after sustaining unstable C6-T4 spinal fractures in a rollover motor vehicle collision. The patient’s point-of-care glucose was between 204 and 343 with a hemoglobin A_1c of 7.7 managed on sliding scale insulin therapy upon admission. This was previously poorly controlled on insulin human isophane (100 units), glyburide (5 mg), and metformin (500 mg). The patient’s erythrocyte sedimentation rate was 81 and their elevated C-reactive protein was 16.8. Additionally, the patient had elevated liver enzymes with alkaline phosphatase (277 U/L), alanine aminotransferase (65 U/L), and aspartate aminotransferase (43 U/L). The patient’s neurological function was fully oriented, level of consciousness appropriate for age, cranial nerves II-XII intact, motor strength equal and normal bilaterally, sensation equal and normal bilaterally, and speech was normal. Pressures were elevated and managed on 10 mg of amlodipine daily. Three days after discharge to a rehabilitation facility, the patient developed dermal dehiscence at the caudad aspect of the wound and a surgical site infection. She was readmitted to the authors’ facility and was found to have purulent drainage from the open wound with surrounding moist eschar and a tunnel measuring at least 6.2 cm at the 12 o’clock position (Figure 2A). A CT scan revealed a small abscess in the posterior soft tissues measuring approximately 2.5 cm × 1.5 cm. Cultures were taken in the OR after the identification of the spinal epidural abscess. The patient was started on meropenem and vancomycin as the wound and blood cultures demonstrated Enterobacter cloacae and Acinetobacter pittii preoperatively. The wound was dressed with silver-impregnated antimicrobial dressing and covered with the silver dressing. 

The patient was taken to the OR for debridement and PUBM application 5 days after readmission. The wound tunneled to the most cephalad aspect of the surgical scar. Exposed hardware and bone graft material was affected from the C5 to T5 level resulting in a wound size of 21 cm × 7 cm × 5 cm. The wound was debrided and irrigated. Autograft bone fragments installed during the previous surgery were removed, cleansed, and reimplanted. A 3-layered PUBM wound sheet measuring 10 cm × 15 cm was then hydrated, delaminated, and secured to the subcutaneous tissue to adequately cover all exposed hardware and bone from the C5 to T5 levels. A 15 French Blake drain (Ethicon) then was placed directly on top of the PUBM for additional drainage (Figure 2B). The skin edges were then approximated with interrupted 3-0 nylon vertical mattress sutures (Figure 2C), after which absorbent dressings, soft silicone foam dressings, and silver-impregnated surgical dressings were applied. The patient was admitted after initial surgery for the wound and repeat debridements (ie, both in the same admission). Postoperatively, the patient did quite well and was seen by infectious disease who recommended 6 weeks of ertapenem therapy. 

ECM is primarily made of collagen and used as a scaffold to promote constructive tissue remodeling. ECM comes in many forms, including sheets and powder. Although the exact mechanism of ECM-induced tissue remodeling is unknown, it is hypothesized that growth factor and cytokine content in addition to collagen, laminins, and other binding molecules play an important role.³ PUBM is a non-crosslinked, resorbable, acellular material derived from the lamina propria of porcine urinary bladder. It is used as an ECM scaffold to induce reconstruction of native tissue with minimal scar tissue. Such xenografts must be extensively processed before use to prevent an immunologic rejection and to decrease risk of infection. An advantage to using PUBM to promote wound healing is its eventual resorption. In treatment of periocular skin defects, complete resorption and replacement of a xenograft by native tissue took 21 days.⁴ Crosslinked scaffolds are less readily absorbed compared to non-crosslinked scaffolds, such as PUBM. Another advantage of PUBM is its antimicrobial properties, as it can recruit white blood cells including macrophages and neutrophils into the scaffold.⁵ ECM scaffolds also have been shown to facilitate site-appropriate host tissue remodeling in skeletal muscle, esophageal tissue, and the urinary tract.⁵ The flexibility of scaffolds, including varying forms and ability to be shaped to the wound’s dimensions, allows physicians to manage complex wound management and reconstruction.

The presence of a CSF fistula complicates wound closure, as it increases the risk of meningitis, excludes the use of negative pressure wound therapy, and often requires prolonged antibiotic therapy and hospitalization. Treatment of CSF fistulas has been controversial and various methods have been posited, such as bedrest, oversewing of the wound, closed subarachnoid drainage, percutaneous injection of an epidural blood patch, and even reoperation for repair of the dura mater.⁶ Early intervention with PUBM in future cases could potentially decrease hospital length of stay and greatly reduce health care costs. Upon review of the literature, the authors found no documented cases of successful use of PUBM for treatment of CSF fistulas. As there is not one clearly superior method to treating this neurosurgical issue, the authors believe that use of PUBM could be implemented for successful sutureless closure of these wounds.

Postoperative spinal infections are a complication that can put patients at risk of returning to the OR, worsened long-term outcomes, and even death.⁷ The incidence varies with the type of operation performed and the specific surgical approach and can vary from 0% to 18%.⁸ The gold standard for diagnosis of postoperative spinal infection is a positive deep wound culture; however, erythrocyte sedimentation rate, C-reactive protein, and CT and magnetic resonance imaging scans have all been demonstrated to be useful diagnostic indicators.⁷ Management of these wounds can be difficult and involves long-term antibiotic therapy, repeat surgical debridement, and possibly even sepsis protocol.⁷ Debridement may be complicated by poor vascularity of the tissue bed and may result in repeat debridement. NPWT or primary closure is traditionally used after debridements.⁷ NPWT was not used due to concerns of CSF leak, increased time for healing, pain, and uncomfortable location of the potential NPWT. PUBM provides an alternative treatment for these wounds that may be more challenging to manage and require repeat debridements. Case 1 highlights definitive closure of a chronic 29-day-old wound with a CSF fistula achieved in 12 days using PUBM application and sutureless skin edge apposition. In case 2, successful wound closure was achieved in 2 weeks after admission with PUBM intervention and no complications had resulted at the time of 1-month follow-up. 

In addition to decreased complications and wound healing over a shortened time frame, there is a cost benefit to both the health care system and patient. The patient in case 1 was in the ICU for a total of 29 days with a chronic wound owing to failure of closure. According to a 2005 study analyzing the cost of an ICU stay, the first day averages $6667 US dollars, the second day $3496 US dollars, and after the third day the cost is relatively stable at $3184 US dollars.⁹ According to these calculations, the cost for a 29-day stay in the ICU for the patient in case 1 was approximately $96 131 US dollars. This cost is likely underestimated, as these data were collected about 20 years ago. Following application of PUBM, the patient was discharged in 3 days. Studies measuring cost of ICU stay are still being completed to present day. ICU costs vary throughout different states and regions, even these studies used data regarding costs from 2013.¹⁰

Limitations include the small number of patients in which the therapy has been utilized. This is especially true for these complex neurosurgical wounds. Often, other more traditional methods are used. It was only after repeated failure of therapies that the authors’ wound management methods were initiated. In addition to this, the ICU costs are an estimate. ICU costs were calculated from a 2005 study and did not account for inflation, changes in protocol since that time, or the fact that these prices could range at the national level. 

This report highlights a unique application of PUBM in 2 neurosurgical wound cases. Neurosurgical wounds and resulting complications can require complex intervention and management that may result in life-long consequences for patients. From these cases, it can be inferred that PUBM may provide an alternative early intervention in wounds that are difficult to manage or in which traditional methods of closure are not successful.

These methods can be beneficial for difficult-to-manage wounds such as CSF fistulas, which do not have an empiric standard method of treatment widely used by physicians. PUBM accelerated wound healing in case 1, facilitating discharge 3 days after application. This is after the patient’s ICU stay had been complicated by a wound that had not healed for 29 days. CSF fistula wounds are traditionally difficult to close. To the authors’ knowledge, this is the first documented use of PUBM technology for closure of a CSF fistula, which was successfully achieved. Not only do these cases highlight accelerated wound healing, especially in the span of 12 days for case 2, but also emphasizes that early intervention of such wounds could result in great cost reduction for both the patient and the health care system.