Spinal fixation after laminectomy in pigs prevents postoperative spinal cord injury

BACKGROUND: A safe, effective, and ethically sound animal model is essential for preclinical research to investigate spinal medical devices. We report the initial failure of a porcine spinal survival model and a potential solution by fixating the spine. METHODS: Eleven female Dutch Landrace pigs underwent a spinal lumbar interlaminar decompression with durotomy and were randomized for implantation of a medical device or control group. Magnetic resonance imaging (MRI) was performed before termination. RESULTS: Neurological deficits were observed in 6 out of the first 8 animals. Three of these animals were terminated prematurely because they reached the predefined humane endpoint. Spinal cord compression and myelopathy was observed on postoperative MRI imaging. We hypothesized postoperative spinal instability with epidural hematoma, inherent to the biology of the model, and subsequent spinal cord injury as a potential cause. In the subsequent 3 animals, we fixated the spine with Lubra plates. All these animals recovered without neurological deficits. The extent of spinal cord compression on MRI was variable across animals and did not seem to correspond well with neurological outcome. CONCLUSION: This study shows that in a porcine in vivo model of interlaminar decompression and durotomy, fixation of the spine after lumbar interlaminar decompression is feasible and may improve neurological outcomes. Additional research is necessary to evaluate this hypothesis

Minimizing complications in a porcine survival craniotomy model

A large craniotomy survival porcine model is useful for scientific research. The surgical approaches and complications of craniotomies in pigs have not been published before. This study describes how large craniotomies were performed in 46 pigs and how the risk of complications was minimized. The major complications were direct postoperative epidural hematomas (n = 3) and sagittal sinus rupture (n = 4). The measures taken to prevent postoperative epidural hematomas consisted of optimizing anesthesia, using bone wax to stop trabecular bleeding, increasing blood pressure before bone flap replacement, tranexamic acid administration, and postoperative recovery of the pigs in the prone position in a dedicated hammock. After these measures, no pig died from a postoperative epidural hematoma. Iatrogenic sagittal sinus rupture occurred in cases where the dura shifted into the craniotome during craniotomy. The dura was detached from the skull through drill holes with custom elevators before craniotomy to minimize the risk of a sagittal sinus rupture. In conclusion, pigs can undergo craniotomy and survive if the right measures are put in place

Usefulness of Sealants for Dural Closure: Evaluation in an In Vitro Model

BACKGROUND Cerebrospinal fluid (CSF) leakage occurs in 4% to 32% of cranial surgeries and is associated with significant patient burden and expense. The use of sealant as an adjunct to primary dural closure is assumed to help prevent CSF leakage. OBJECTIVE To examine the utility of different sealants for dural closure using an in Vitro model. METHODS We evaluated 9 commonly used dural sealants, including Tachosil (Takeda Inc, Osaka, Japan), Adherus (Hyperbranch Inc, Durham, North Carolina), Duraform (Codman, Raynham, Massachusetts), Tissudura (Baxter, Deerfield, Illinois), Hemopatch (Baxter), TissuePatchDural (Tissuemed, Leeds, United Kingdom), Tisseel (Baxter), Duragen Secure (Integra, Plainsboro, New Jersey), and Duraseal, (Integra). Sealants were tested in 2 novel in Vitro setups using fresh porcine dura: the first tested the acute burst pressure of a sealed 3-mm gap, while the second examined resistance to a pressure wave mimicking intracranial pressure for 72 h. RESULTS Adherus showed the highest mean burst pressure (87 ± 47 mmHg) followed by Tachosil (71 ± 16 mmHg) and Duraseal (51 ± 42 mmHg); these were the only 3 sealants showing burst pressures above normal physiological intracranial pressure. In the 72-h setup, only Adherus and Duraseal maintained appropriate sealing for the duration of the experiment. Tachosil released from the dura after 1.4 h (95% confidence interval, −1.8-4.7). CONCLUSION Given the high cost of sealants and the results of this study, we advocate a critical attitude toward sealant application as an adjunct to classic dural closure

Usefulness of Sealants for Dural Closure : Evaluation in an In Vitro Model

BACKGROUND: Cerebrospinal fluid (CSF) leakage occurs in 4% to 32% of cranial surgeries and is associated with significant patient burden and expense. The use of sealant as an adjunct to primary dural closure is assumed to help prevent CSF leakage. OBJECTIVE: To examine the utility of different sealants for dural closure using an in Vitro model. METHODS: We evaluated 9 commonly used dural sealants, including Tachosil (Takeda Inc, Osaka, Japan), Adherus (Hyperbranch Inc, Durham, North Carolina), Duraform (Codman, Raynham, Massachusetts), Tissudura (Baxter, Deerfield, Illinois), Hemopatch (Baxter), TissuePatchDural (Tissuemed, Leeds, United Kingdom), Tisseel (Baxter), Duragen Secure (Integra, Plainsboro, New Jersey), and Duraseal, (Integra). Sealants were tested in 2 novel in Vitro setups using fresh porcine dura: the first tested the acute burst pressure of a sealed 3-mm gap, while the second examined resistance to a pressure wave mimicking intracranial pressure for 72 h. RESULTS: Adherus showed the highest mean burst pressure (87 ± 47 mmHg) followed by Tachosil (71 ± 16 mmHg) and Duraseal (51 ± 42 mmHg); these were the only 3 sealants showing burst pressures above normal physiological intracranial pressure. In the 72-h setup, only Adherus and Duraseal maintained appropriate sealing for the duration of the experiment. Tachosil released from the dura after 1.4 h (95% confidence interval, -1.8-4.7). CONCLUSION: Given the high cost of sealants and the results of this study, we advocate a critical attitude toward sealant application as an adjunct to classic dural closure

Safety and biodegradability of a synthetic dural sealant patch (Liqoseal) in a porcine cranial model

Background Liqoseal consists of a watertight layer of poly(ester)ether urethane and an adhesive layer containing polyethylene glycol-N-hydroxysuccinimide (PEG-NHS). It is designed to prevent cerebrospinal fluid (CSF) leakage after intradural surgery. This study assessed the safety and biodegradability of Liqoseal in a porcine craniotomy model. Methods In 32 pigs a craniotomy plus durotomy was performed. In 15 pigs Liqoseal was implanted, in 11 control pigs no sealant was implanted and in 6 control pigs a control dural sealant (Duraseal or Tachosil) was implanted. The safety of Liqoseal was evaluated by clinical, MRI and histological assessment. The degradation of Liqoseal was histologically estimated. Results Liqoseal, 2 mm thick before application, did not swell and significantly was at maximum mean thickness of 2.14 (±0.37) mm at one month. The foreign body reaction induced by Liqoseal, Duraseal and Tachosil were comparable. Liqoseal showed no adherence to the arachnoid layer and was completely resorbed between 6 and 12 months postoperatively. In one animal with Liqoseal, an epidural fluid collection containing CSF could not be excluded. Conclusion Liqoseal seems to be safe for intracranial use and is biodegradable. The safety and performance in humans needs to be further assessed in clinical trials

Safety and biodegradability of a synthetic dural sealant patch (Liqoseal) in a porcine cranial model

Background: Liqoseal consists of a watertight layer of poly(ester)ether urethane and an adhesive layer containing polyethylene glycol-N-hydroxysuccinimide (PEG-NHS). It is designed to prevent cerebrospinal fluid (CSF) leakage after intradural surgery. This study assessed the safety and biodegradability of Liqoseal in a porcine craniotomy model. Methods: In 32 pigs a craniotomy plus durotomy was performed. In 15 pigs Liqoseal was implanted, in 11 control pigs no sealant was implanted and in 6 control pigs a control dural sealant (Duraseal or Tachosil) was implanted. The safety of Liqoseal was evaluated by clinical, MRI and histological assessment. The degradation of Liqoseal was histologically estimated. Results: Liqoseal, 2 mm thick before application, did not swell and significantly was at maximum mean thickness of 2.14 (±0.37) mm at one month. The foreign body reaction induced by Liqoseal, Duraseal and Tachosil were comparable. Liqoseal showed no adherence to the arachnoid layer and was completely resorbed between 6 and 12 months postoperatively. In one animal with Liqoseal, an epidural fluid collection containing CSF could not be excluded. Conclusion: Liqoseal seems to be safe for intracranial use and is biodegradable. The safety and performance in humans needs to be further assessed in clinical trials

Usefulness of Sealants for Dural Closure: Evaluation in an In Vitro Model

BACKGROUND: Cerebrospinal fluid (CSF) leakage occurs in 4% to 32% of cranial surgeries and is associated with significant patient burden and expense. The use of sealant as an adjunct to primary dural closure is assumed to help prevent CSF leakage. OBJECTIVE: To examine the utility of different sealants for dural closure using an in Vitro model. METHODS: We evaluated 9 commonly used dural sealants, including Tachosil (Takeda Inc, Osaka, Japan), Adherus (Hyperbranch Inc, Durham, North Carolina), Duraform (Codman, Raynham, Massachusetts), Tissudura (Baxter, Deerfield, Illinois), Hemopatch (Baxter), TissuePatchDural (Tissuemed, Leeds, United Kingdom), Tisseel (Baxter), Duragen Secure (Integra, Plainsboro, New Jersey), and Duraseal, (Integra). Sealants were tested in 2 novel in Vitro setups using fresh porcine dura: the first tested the acute burst pressure of a sealed 3-mm gap, while the second examined resistance to a pressure wave mimicking intracranial pressure for 72 h. RESULTS: Adherus showed the highest mean burst pressure (87 ± 47 mmHg) followed by Tachosil (71 ± 16 mmHg) and Duraseal (51 ± 42 mmHg); these were the only 3 sealants showing burst pressures above normal physiological intracranial pressure. In the 72-h setup, only Adherus and Duraseal maintained appropriate sealing for the duration of the experiment. Tachosil released from the dura after 1.4 h (95% confidence interval, -1.8-4.7). CONCLUSION: Given the high cost of sealants and the results of this study, we advocate a critical attitude toward sealant application as an adjunct to classic dural closure

Histological and magnetic resonance imaging assessment of Liqoseal in a spinal in vivo pig model

BACKGROUND Liqoseal (Polyganics, B.V.) is a dural sealant patch for preventing postoperative cerebrospinal fluid (CSF) leakage. It has been extensively tested preclinically and CE (Conformité Européenne) approved for human use after a first cranial in-human study. However, the safety of Liqoseal for spinal application is still unknown. The aim of this study was to assess the safety of spinal Liqoseal application compared with cranial application using histology and magnetic resonance imaging characteristics. METHODS Eight female Dutch Landrace pigs underwent laminectomy, durotomy with standard suturing and Liqoseal application. Three control animals underwent the same procedure without sealant application. The histological characteristics and imaging characteristics of animals with similar survival times were compared to data from a previous cranial porcine model. RESULTS Similar foreign body reactions were observed in spinal and cranial dura. The foreign body reaction consisted of neutrophils and reactive fibroblasts in the first 3 days, changing to a chronic granulomatous inflammatory reaction with an increasing number of macrophages and lymphocytes and the formation of a fibroblast layer on the dura by day 7. Mean Liqoseal plus dura thickness reached a maximum of 1.2 mm (range 0.7-2.0 mm) at day 7. CONCLUSION The spinal dural histological reaction to Liqoseal during the first 7 days was similar to the cranial dural reaction. Liqoseal did not swell significantly in both application areas over time. Given the current lack of a safe and effective dural sealant for spinal application, we propose that an in-human safety study of Liqoseal is the logical next step

Safety and biodegradability of a synthetic dural sealant patch (Liqoseal) in a porcine cranial model

Background: Liqoseal consists of a watertight layer of poly(ester)ether urethane and an adhesive layer containing polyethylene glycol-N-hydroxysuccinimide (PEG-NHS). It is designed to prevent cerebrospinal fluid (CSF) leakage after intradural surgery. This study assessed the safety and biodegradability of Liqoseal in a porcine craniotomy model. Methods: In 32 pigs a craniotomy plus durotomy was performed. In 15 pigs Liqoseal was implanted, in 11 control pigs no sealant was implanted and in 6 control pigs a control dural sealant (Duraseal or Tachosil) was implanted. The safety of Liqoseal was evaluated by clinical, MRI and histological assessment. The degradation of Liqoseal was histologically estimated. Results: Liqoseal, 2 mm thick before application, did not swell and significantly was at maximum mean thickness of 2.14 (±0.37) mm at one month. The foreign body reaction induced by Liqoseal, Duraseal and Tachosil were comparable. Liqoseal showed no adherence to the arachnoid layer and was completely resorbed between 6 and 12 months postoperatively. In one animal with Liqoseal, an epidural fluid collection containing CSF could not be excluded. Conclusion: Liqoseal seems to be safe for intracranial use and is biodegradable. The safety and performance in humans needs to be further assessed in clinical trials

Targeting prolyl endopeptidase with valproic acid as a potential modulator of neutrophilic inflammation

A novel neutrophil chemoattractant derived from collagen, proline-glycine-proline (PGP), has been recently characterized in chronic obstructive pulmonary disease (COPD). This peptide is derived via the proteolytic activity of matrix metalloproteases (MMP's)-8/9 and PE, enzymes produced by neutrophils and present in COPD serum and sputum. Valproic acid (VPA) is an inhibitor of PE and could possibly have an effect on the severity of chronic inflammation. Here the interaction site of VPA to PE and the resulting effect on the secondary structure of PE is investigated. Also, the potential inhibition of PGP-generation by VPA was examined in vitro and in vivo to improve our understanding of the biological role of VPA. UV-visible, fluorescence spectroscopy, CD and NMR were used to determine kinetic information and structural interactions between VPA and PE. In vitro, PGP generation was significantly inhibited by VPA. In vivo, VPA significantly reduced cigarette-smoke induced neutrophil influx. Investigating the molecular interaction between VPA and PE showed that VPA modified the secondary structure of PE, making substrate binding at the catalytic side of PE impossible. Revealing the molecular interaction VPA to PE may lead to a better understanding of the involvement of PE and PGP in inflammatory conditions. In addition, the model of VPA interaction with PE suggests that PE inhibitors have a great potential to serve as therapeutics in inflammatory disorders