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...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.展开更多
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)leak...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.展开更多
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 (Conformite Européenne) approved f...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 (Conformite 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 first3 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 1.2mm(range 0.7-2.0mm) at day 7.Conclusion:The spinal dural histological reaction to Liqoseal during the first 7days 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.展开更多
基金supported by a research grant from ZonMw(114024064)。
文摘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.
文摘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.
文摘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 (Conformite 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 first3 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 1.2mm(range 0.7-2.0mm) at day 7.Conclusion:The spinal dural histological reaction to Liqoseal during the first 7days 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.
