BiomaterialsLecture8

SourceInformationforthefollowingslides: 1)B.Ratner,A.Hoffman,F.Schoen,andJ.Lemons:BiomaterialsScience, 2nd edition(SanDiego:ElsevierAcademicPress.2004).

CaseStudy?
PainLeadsArtProfessortoRemove"ThirdEye"CameraFromHead AnassistantartsprofessoratNewYorkUniversity,neededtoremovethe camerahehadinstalledintothebackofhisheadearlierthismonth becausehisbodyrejectedtheforeignobject. Perhapsoneoftheprimaryproblems: Thecamera,whichwasimplantedbetweenhisskinandhisskullinaL.A. tattooshop. Biocompatability Titaniumposts

Hydrogels

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Definition
waterinsoluble,threedimensionalnetworkofpolymericchains thatarecrosslinked bychemicalorphysicalbonding; polymerscapableofswellingsubstantiallyinaqueous conditions(e.g.hydrophilic) polymericnetworkinwhichwaterisdispersedthroughoutthe structure

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Crosslinksmaybephysicalor chemical:
byreactionofoneor moremonomerswith pendantfunctional groups hydrogenorionic bonding,or vanderWaals interactions

_ _ _ _

_ _ + +

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Hydrogels
Oneormorehighlyelectronegativeatomswhichresultsin chargeasymmetryfavoringhydrogenbondingwithwater; Becauseoftheirhydrophilicnaturedrymaterialsabsorb water; Bydefinition,watermustconstituteatleast10%ofthetotal weight(orvolume)foramaterialstobeahydrogel; Whenthecontentofwaterexceeds95%ofthetotalweight (orvolume),thehydrogelissaidtobesuperabsorbant;

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Classificationbasedonpreparationmethod
homopolymer hydrogels(onetypeofhydrophilicmer) copolymerhydrogels(twotypesofmers,atleastone hydrophilic) multipolymer hydrogels(morethanthreetypesofmers) interpenetratingpolymerichydrogels(swellinganetwork ofpolmer1 inmer2,makingintermeshingnetworkof polymer1 andpolymer2)

Hydrogels
Classificationbasedonioniccharges
neutralhydrogels anionichydrogels cationichydrogels ampholytic hydrogels

Classificationbasedonstructure
amorphoushydrogels(chainsrandomlyarranged) semicrystalline hydrogels(denseregionsofordered macromolecules,i.e.crystallites) hydrogenbondedhydrogels
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PreparationofHydrogels

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Hoffman,A.S.Adv.DrugDeliv.Rev.,2002,43,3

Hydrogels:

Inachemicallycrosslinkedhydrogel,allofthepolymerchainsare connectedbycovalentbondstoformanetwork;and,thus Canbeviewedasoneone moleculeoflargesize; Thethermodynamicallydrivenswellingforceiscounterbalancedbythe retractive forceofthecrosslinked structure; Theuniquepropertyofthesegelsisthereabilitytomaintaintheiroriginal shapeduringandafterswelling; Twoforcesbecomeequalatsomepointandequilibriumisreached

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Hydrogels:Swelling

Degreeofswellingcanbequantifiedby: ratioofsamplevolumeintheswollenstatetovolumein thedrystate(Q)

Vp Volume of polymer 1/ Q v2, s Volume of swollen gel Vgel where v 2 , s is the polymer volume fraction of the gel

weightdegreeofswelling:ratiooftheweightofswollen sampletothatofthedrysample(q)

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Hydrogels:Swelling

Whyisthedegreeofswellingimportant? solutediffusioncoefficientthroughthehydrogel surfacepropertiesandsurfacemobility opticalproperties(particularlyforcontactlens applications) mechanicalproperties

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StructuralCharacteristics
M c (Molecular weight between crosslinks) Defines the average molecular weight between two consecutive junctions,
2 1 2 ( / V1 ) ln(1 2, s ) 2, s 1 2, s 1/ 3 2 Mc Mc , s 2 , s / 2)

where 1 is polymer - water interaction parameter

is the reciprocal of the amorphous polymer density (specific volume of polymer)

Crosslink density 1 x Mc

Hydrogels
Crosslinkstructure:
A) idealnetworkwith tetrafunctionalcovalent crosslinks(rarely observed) B) multifunctionaljunctions C) molecularentanglements (couldbepermanentor semipermanent)
Mc:Molecularweightbetween crosslinks
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Hydrogels
Defectsincrosslinkstructure:
D)unreactedfunctionality E)chainloops

Notethatneitherofthetwo configurationscontributeto mechanicalstrengthor physicalpropertiesofthe network

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Importantfeaturesofhydrogels
Usuallycomprisedofhighlypolyionicpolymers Oftenexhibitlargevolumetricchangeseg.Highly compressedinsecretoryvessicleandexpand rapidly anddramaticallyonrelease Canundergovolumetricphasetransitionsin responsetoionicconcentrations(Ca++,H+), temperature,.. Volumeisdeterminedbycombinationof attractiveandrepulsiveforces:
repulsiveelectrostatic,hydrophobic attractive,hydrogenbinding,crosslinking

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Xerogels
Driedhydrogels Usuallyclearandswellinginwatertakesalongtime; Theswellingbehaviorisduetoslowdiffusionofwater throughthecompactpolymerchains; Ausefulpropertyincontrolleddrugdelivery;

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Chitosan

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Applications
Pharmaceuticalapplications
monomercompositionandrelativeamountsofmultipolymer hydrogelscanbevariedtoalterthediffusioncharacteristicand permeabilityofthegelcontainingpharmaceuticalagents

Methodsfordrugdelivery
druggetstrappedinthehydrogelduringpolymerization drugintroducedduringswellinginwater Releaseoccursbyoutflowofdrugfromthegelandinflowof watertothegel

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Drugdelivery

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Examplesofbiologicalhydrogels:

Jello(acollagengel~97%water) Extracellularmatrixcomponents Polysaccharides DNA/RNA Bloodclot Mucin liningthestomach,bronchialtubes,intestines Gycocalyx liningepithelialcellsofbloodvessels Sinussecretions
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FibrinHydrogel(BloodClot)

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Functionofabiologicalhydrogel
Decreasedpermeabilitytolargemolecules Structuralstrength(forepithelialcellwalls) Captureandclearanceofforeignsubstances Decreasedresistancetosliding/gliding Highinternalviscosity(lowwashout)

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HydrogelFormingPolymers
Natural
H O 2C HO O HO O OH HO O NH O O n poly(s odium alginate) NaO 2 C HO OH O O n

poly(hyaluronic acid)

Synthetic
O O n O n NH O n

poly(lactic acid)

poly(N is opropyl acrylamide)

poly(ethylene g lycol)

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Hydrogels
Highlyswollenhydrogels:
cellulosederivatives poly(vinylalcohol) poly(Nvinyl2pyrrolidone),PNVP poly(ethyleneglycol) poly(hydroxyethyl methacrylate),PHEMAandderivatives

Moderatelyorpoorlyswollenhydrogels:

Onemaycopolymerizeahigly hydrophilicmonomerwithother lesshydrophilicmonomerstoachievedesiredswelling properties

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HylauronicAcid

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PolyelectrolyteHydrogels

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Alginategels
linkage

linkage

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Alginategels

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EnzymeImmobilization

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CellEncapsulation

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ApplicationsinBiomaterialsandTissue Engineering CellEncapsulation Drugdelivery Surfacemodification EnzymeImmobilization Biosensors Labonachip

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Hydrogels:PHEMA

Themostwidelyusedhydrogel watercontentsimilartolivingtissues inerttobiologicalprocesses showsresistancetodegradation permeabletometabolites notabsorbedbythebody withstandssterilizationbyheat preparedinvariousshapedandforms

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Hydrogels:Applications

Biomedicaluseduetobio andbloodcompatibility Pharmaceuticaluseduetohydrophilicity (controlled/sustaineddrug release) Earliestbiomedicalapplicationcontactlenses goodmechanicalstability favorablerefractiveindex highoxygenpermeability needshygienicmaintenance unabletocorrectforastigmatism lubricatingsurfacecoating usedwithcatheters,drainagetubesandgloves nontoxic

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Corning Ultra Low Attachment Products Unique hydrogel surface inhibits cell attachment

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OcularDrugDelivery

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Applications
artificialtendonandcartilage woundhealingdressings(Vigilon,Hydron, Gelperm)
nonantigenic,flexiblewoundcover permeabletowaterandmetabolites lowstrength

artificialkidneymembranes artificialskin maxillofacialandsexualorganreconstructionmaterials vocalcordreplacement

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Applications
Pharmaceuticalapplications
monomercompositionandrelativeamountsofmultipolymer hydrogelscanbevariedtoalterthediffusioncharacteristicand permeabilityofthegelcontainingpharmaceuticalagents

Methodsfordrugdelivery
druggetstrappedinthehydrogelduringpolymerization drugintroducedduringswellinginwater Releaseoccursbyoutflowofdrugfromthegelandinflowof watertothegel

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Contactlens
PMMA HEMA Fabricationmethods
Computerassistedcutting(lathe)PMMArods Spincastingpolymerization Moldingpolymerization

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