Hydrogels for Coating Hydrogels for Coating Medical DevicesMedical Devices

University of WisconsinUniversity of Wisconsin

BME 400BME 400

Our TeamOur Team

Benjamin Roedl – Team LeaderBenjamin Roedl – Team LeaderPatrick Schenk – Communicator Patrick Schenk – Communicator Darshan Patel – BWIGDarshan Patel – BWIGBrett Mulawka - BSACBrett Mulawka - BSAC

Client & AdvisorClient & Advisor

Client: Client: Arthur J. Coury, Ph.D. Arthur J. Coury, Ph.D. Vice President Biomaterials Research Vice President Biomaterials Research

Genzyme CorporationGenzyme CorporationAdvisor: William Murphy, Professor of Advisor: William Murphy, Professor of

Biomedical EngineeringBiomedical Engineering

Problem StatementProblem Statement

To form PEG based hydrogels on To form PEG based hydrogels on biomaterial surfaces in an interfacial biomaterial surfaces in an interfacial photopolymerization process and to photopolymerization process and to screen the coatings for interactions with screen the coatings for interactions with cells and media that mimic physiologic cells and media that mimic physiologic fluids. It is hypothesized that these fluids. It is hypothesized that these coatings will resist fouling and may be coatings will resist fouling and may be useful for implantable devices.useful for implantable devices.

Genzyme CorporationGenzyme Corporation

One of world’s foremost biotechnology One of world’s foremost biotechnology companies with the goal of applying the companies with the goal of applying the most advanced technologies to address most advanced technologies to address unmet medical needs. unmet medical needs.

MotivationMotivation

Development of blood compatible hydrogel Development of blood compatible hydrogel could have many applicationscould have many applicationsOrthopedic applicationsOrthopedic applicationsUrinary CatheterUrinary CatheterTissue RepairTissue Repair

Create a hydrogel application procedure Create a hydrogel application procedure that results in accurate and reproducible that results in accurate and reproducible resultsresults

Background-HydrogelsBackground-Hydrogels

Polymeric structures that absorbs waterPolymeric structures that absorbs water Crosslinks, Polymer, Liquid (Water)Crosslinks, Polymer, Liquid (Water)

CrosslinkingCrosslinking

Covalent Bonds Linking One Covalent Bonds Linking One Polymer Chain to AnotherPolymer Chain to Another

Can be Caused by Heat, Can be Caused by Heat, Pressure, ChemicalsPressure, Chemicals Form free radicalsForm free radicals We use a chemical that is light We use a chemical that is light

initiatedinitiated

By Crosslinking, Hydrogels By Crosslinking, Hydrogels are Capable of Remarkable are Capable of Remarkable Water Retention/AdsorptionWater Retention/Adsorption

Polyethylene Glycol (PEG)Polyethylene Glycol (PEG)

PropertiesPropertiesClear, viscous, odorless, miscible in water, Clear, viscous, odorless, miscible in water,

non-toxicnon-toxic

UsesUsesWound dressing, soft tissue replacement, Wound dressing, soft tissue replacement,

drug delivery.drug delivery.

Eosin YEosin Y

One Part of a Two One Part of a Two Part Photoinitiator Part Photoinitiator SystemSystem

Maximum Adsorption Maximum Adsorption at 514 nm (visible)at 514 nm (visible)

Passes Free Radical Passes Free Radical to Triethanolamineto Triethanolamine

Taken from OLMC.Ogi.edu

TriethanolamineTriethanolamine

Accepts Free Radical Accepts Free Radical from Eosin Yfrom Eosin Y

Combines with Combines with Macromer to Macromer to polymerize reactionpolymerize reaction

Visible Light Initiating System

O

COO

Br

O

BrBr

Br

O

O

COO

Br

OH

BrBr

Br

OO

COO

Br

O

BrBr

Br

ONa

Na

Na

Na

NaNa

H

:N(CH2CH2OH)2

CHCH2OH

:N(CH2CH2OH)3

Na

514 nm [Eosin Y]*

POLYMERIZATION

+

+

Eosin Y

Macromer +

ProcedureProcedure

Stain specimen with Eosin SolutionStain specimen with Eosin Solution Immerse stained specimen in macromer Immerse stained specimen in macromer

solutionsolutionApply visible lightApply visible lightAn adherent, thin, hydrogel forms by An adherent, thin, hydrogel forms by

polymerization of the macromer (PEG)polymerization of the macromer (PEG)Expose specimen to cells to test for foulingExpose specimen to cells to test for fouling

Interfacial Polymerization

TestingTesting

ThicknessThicknessNeed to maintain consistent thickness for Need to maintain consistent thickness for

reliable test data / Toughnessreliable test data / ToughnessAdherenceAdherence

Durability through many cyclesDurability through many cyclesFouling ResistanceFouling Resistance

BiocompatibilityBiocompatibilityMost importantMost important

ThicknessThickness

Place fully swollen coated substrate on Place fully swollen coated substrate on edge under optical microscopeedge under optical microscopeMicroscope with camera would be idealMicroscope with camera would be ideal

Hydrogel thickness goal: 25 – 100 micronsHydrogel thickness goal: 25 – 100 micronsAlternate method:Alternate method:

Peel/slice piece of gel off at interface, cut to Peel/slice piece of gel off at interface, cut to straight edge and measure with optical straight edge and measure with optical microscopemicroscope

AdherenceAdherence

Using a pointed spatula or needle, one Using a pointed spatula or needle, one person (control) will estimate adherence person (control) will estimate adherence on a specific scaleon a specific scale0 = Has fallen off0 = Has fallen off1 = Lifts off almost intact with mild force1 = Lifts off almost intact with mild force- 2 = Lifts off in large chunks with some force2 = Lifts off in large chunks with some force- 3 = Lifts off in small pieces with some force3 = Lifts off in small pieces with some force- 4 = Does not delaminate even by destroying 4 = Does not delaminate even by destroying

gel with pushing forcegel with pushing force

Fouling ResistanceFouling Resistance

Expose to proteins Expose to proteins found in blood in found in blood in solutionsolution

Stain with appropriate Stain with appropriate dye to view adhered dye to view adhered proteinsproteins

Future Work:Future Work:Protein AdsorptionProtein Adsorption

Determine the concentration of proteins Determine the concentration of proteins we must measurewe must measure

Establish the best protein assay method to Establish the best protein assay method to useuseAcceptable resolutionAcceptable resolutionEase of procedureEase of procedure

UV adsorption, BCA assay… etcUV adsorption, BCA assay… etc

ReferencesReferences

Arthur J. Coury, Ph.D.Arthur J. Coury, Ph.D. Kenneth MessierKenneth Messier McNair, Andrew M. "Using Hydrogel Polymers for McNair, Andrew M. "Using Hydrogel Polymers for

Drug Delivery." Drug Delivery." Medical Device TechnologyMedical Device Technology (1996). (1996). Kizilel, Seda, Victor H. Perez-Luna, and Fouad Kizilel, Seda, Victor H. Perez-Luna, and Fouad

Teymour. "Photopolymerization of Poly(Ethylene Teymour. "Photopolymerization of Poly(Ethylene Glycol) Diacrylate on Eosin-Functionalized Glycol) Diacrylate on Eosin-Functionalized Surfaces." Surfaces." LangmuirLangmuir (2004). (2004).

Thank youThank you

Questions?Questions?

Hydrogel PreparationHydrogel Preparation Radical chain reaction used to form cross linksRadical chain reaction used to form cross links

Initiated using electrons, gamma-rays, x-rays, UV light to excite polymer Initiated using electrons, gamma-rays, x-rays, UV light to excite polymer chain and form radicalschain and form radicals

(We will use visible light 514nm for eosin)(We will use visible light 514nm for eosin)

CrosslinkersCrosslinkers Acrylate, double bond forms radicalAcrylate, double bond forms radical

Polyethylene Glycol (PEG)Polyethylene Glycol (PEG)

Non-toxicNon-toxic Laxatives, Skin Laxatives, Skin

Creams, LubricantsCreams, Lubricants

Light SourceLight Source

Using a xenon light sourceUsing a xenon light sourceApplied to sample for 40 Seconds at a Applied to sample for 40 Seconds at a

Distance of One InchDistance of One InchLight Source Supplies Energy to Remove Light Source Supplies Energy to Remove

Electron from Eosin YElectron from Eosin YLeads to a propagation of crosslinking Leads to a propagation of crosslinking

between the macromer and triethanolaminebetween the macromer and triethanolamine