Biocompatibility of Biocompatibility of Polyimide Based Neural Polyimide Based Neural

Devices for Chronic Devices for Chronic Implant Applications Implant Applications

Samantha WatkinsSamantha WatkinsAdvisor: Dr. Patrick J. Advisor: Dr. Patrick J. RouscheRousche

Neural Engineering & Applications LabNeural Engineering & Applications Lab

Gandhi, D 2006 Assessing Chronic Functionality of Photo-Definable Polyimide Based Flexible Neural Interface for the Central Nervous System Preliminary Thesis PhD. Defense Summary.

Neural Device Neural Device ApplicationsApplications

Gandhi, D 2006 Assessing Chronic Functionality of Photo-Definable Polyimide Based Flexible Neural Interface for the Central Nervous System Preliminary Thesis PhD. Defense Summary. & http://bryanbrandenburg.blog.com/Biomedical/

NeuroNeuro Prosthesis Prosthesis –– Restore functionality in Restore functionality in

central nervous system central nervous system tissuetissue

–– Information exchange Information exchange Delivering and recording Delivering and recording electrical signals to and from electrical signals to and from neuronal cellsneuronal cells

Assess the physiological Assess the physiological environment at a cellular environment at a cellular levellevel

LongLong--Term Term BiocompatibilityBiocompatibility

Minimize foreign body response and immune reactionMinimize foreign body response and immune reactionDecrease the risk of scar tissue formationDecrease the risk of scar tissue formation–– Preventing device isolation from surrounding neural tissue Preventing device isolation from surrounding neural tissue

((gliosisgliosis))

The interface should also reduce mechanical The interface should also reduce mechanical micromotionmicromotionstrain which further reduces strain which further reduces gliosisgliosis

Stimulation & RecordingFunctionality

Brain TissueAcceptance

Gandhi, D 2006 Assessing Chronic Functionality of Photo-Definable Polyimide Based Flexible Neural Interface for the Central Nervous System Preliminary Thesis PhD. Defense Summary.

Mechanical ComplianceMechanical Compliance

Mechanical mismatch between materialsMechanical mismatch between materials–– Polyimide has a YoungPolyimide has a Young’’s Modulus 25s Modulus 25--100 times lower than other 100 times lower than other

materialsmaterialsPolyimide flexibility causes buckling during insertionPolyimide flexibility causes buckling during insertionEnhance device strength by with Enhance device strength by with polyglycolicpolyglycolic acid (PGA)acid (PGA)

Mechanical RigidityMechanical Rigidity

MaterialMaterial YoungYoung’’s Moduluss ModulusTungsten Tungsten MicrowireMicrowire 400 400 GPaGPa

SiliconSilicon 120120--140 140 GPaGPa

PolyimidePolyimide 4 4 GPaGPa

Brain TissueBrain Tissue 0.067 0.067 GPaGPa

PGA MaterialPGA Material

Mechanical rigidityMechanical rigidity–– YoungYoung’’s Modulus s Modulus --> 7GPa> 7GPa

FDA approved and biodegradable suture materialFDA approved and biodegradable suture materialGlass transition temperature Glass transition temperature --> 35> 3500CC–– Stable at room temperatures Stable at room temperatures

and degrades once implantedand degrades once implanted

MeltMelt--coating polyimide coating polyimide devices for implant devices for implant applicationsapplications

–– OneOne--sided coatingsided coating

Polymer Material Polymer Material CharacterizationCharacterization

Utilize polymerUtilize polymer--based devices to assess based devices to assess biocompatibility of neural implants in biocompatibility of neural implants in chronic applicationschronic applications–– Uncoated polyimide devicesUncoated polyimide devices–– PGA coated polyimide devicesPGA coated polyimide devices

Monitor tissue response with histology Monitor tissue response with histology techniquestechniques

4 0 0 μm1 4 6 -1 5 6 μm

1 0 0 0 0 μm 4 0 0 0 μm

4 0 0 μm1 4 6 -1 5 6 μm

1 0 0 0 0 μm 4 0 0 0 μm

1 0 0 0 0 μm 4 0 0 0 μm

1 0 0 0 0 μm 4 0 0 0 μm4 0 0 0 μm

Gandhi, D 2006 Assessing Chronic Functionality of Photo-Definable Polyimide Based Flexible Neural Interface for the Central Nervous System Preliminary Thesis PhD. Defense Summary.

Histology MethodsHistology Methods

Device implantDevice implant-- 15 days15 daysFormalin fixationFormalin fixationParaffin embeddingParaffin embedding88μμm sectionsm sectionsH&E stainingH&E staining–– Cell DistributionCell Distribution

Immunochemistry stainingImmunochemistry staining–– GlialGlial fibrillaryfibrillary acidic protein (GFAP), acidic protein (GFAP),

astrocyteastrocyte--specific marker specific marker –– GlialGlial scar formationscar formation

BrightfieldBrightfield microscopy imagingmicroscopy imaging2 Shaft Polyimide Device

500 um

H&E Results H&E Results ––Uncoated Polyimide DevicesUncoated Polyimide Devices

Sections of four implants Sections of four implants at varying depthsat varying depthsNormal cell interactionNormal cell interaction

100 um

100 um 100 um100 um

H&E Results H&E Results ––PGA Coated DevicesPGA Coated Devices

Sections of three implants Sections of three implants at varying depthsat varying depthsNormal cell behaviorNormal cell behavior–– OneOne--sided responsesided response

100 um 100 um100 um

100 um

GFAP Immunochemistry GFAP Immunochemistry Results Results –– Uncoated Polyimide Uncoated Polyimide DevicesDevices

Sections of two implants at Sections of two implants at varying depthsvarying depthsMinimal Minimal glialglial scar scar formation formation

100 um

100 um

100 um 100 um

GFAP ImmunochemistryGFAP ImmunochemistryResults Results —— PGA Coated DevicesPGA Coated Devices

Sections of three implants Sections of three implants at varying depthsat varying depthsMinimal Minimal glialglial scar scar formation formation –– OneOne--sided responsesided response

100 um 100 um 100 um

100 um

ConclusionConclusion

Polyimide material provides mechanical flexibility to Polyimide material provides mechanical flexibility to reduce reduce micromotionmicromotion strainstrainPGA material provides temporary mechanical PGA material provides temporary mechanical rigidity for insertionrigidity for insertion–– In vitro studies in our lab suggest PGA degrades within In vitro studies in our lab suggest PGA degrades within

three daysthree days

Histology results show successful biocompatibility of Histology results show successful biocompatibility of polymer materials with only a slight tissue responsepolymer materials with only a slight tissue responsePolymer materials provide new design strategies for Polymer materials provide new design strategies for

neural devices used in longneural devices used in long--term implantsterm implants

AcknowledgementsAcknowledgements

Grant NSF EEC 0453432Grant NSF EEC 0453432–– National Science Foundation REU National Science Foundation REU

Program Program –– Department of Defense ASSURE ProgramDepartment of Defense ASSURE ProgramDr. Dr. Rousche'sRousche's Research TeamResearch Team–– DevangDevang GandhiGandhi–– Peter Peter TekTek

Biocompatibility of Polyimide Based Neural Devices for Chronic Implant Applications Neural Device ApplicationsLong-Term BiocompatibilityMechanical CompliancePGA MaterialPolymer Material CharacterizationHistology MethodsH&E Results – �Uncoated Polyimide DevicesH&E Results – �PGA Coated DevicesGFAP Immunochemistry �Results – Uncoated Polyimide DevicesGFAP Immunochemistry�Results — PGA Coated DevicesConclusionAcknowledgements