NaturalPolymersasBiomaterials

SourceInformationforthefollowingslides: 1)Okada,M.Prog.Polym.Sci.2002,27,87133. 2)Nair,L.etal.Prog.Polym.Sci.2007,32,762798. 3)B.Ratner,A.Hoffman,F.Schoen,andJ.Lemons:BiomaterialsScience, 2nd edition(SanDiego:ElsevierAcademicPress.2004).

EnzymaticallyDegradablePolymers
ProteinsandPoly(aminoacids) Collagen Naturalpoly(aminoacids) Syntheticpoly(aminoacids)
Poly(Lglutamicacid) Poly(asparticacid)

Elastin Elastinlikepeptides Albumin Fibrin Polysaccharides

Chitinandchitosan

NaturalPolymers:Background
Egypt:Animalsinewusedforsutures 100:Disemboweledsoldierstreatedwithnatural biomaterials 1667:Bloodtransfusionwithlambblood (France) 1700:Caranium transplantationfromdog(Russia) 1936:ArthurBowen(England)usedporcinesmall intestineasasofttissuealternative.Abundant material,lowimmunogenicity

NaturalPolymers:Background
Relevance:naturaltissuesinbiomedicineisamultibillion dollarindustry Fabrication:mostlylivingtissuesfromhumans(autograft, allograft)oranimals(xenograft)thathavebeendecellularized usingsterilants. Applications:Heartvalves,meniscusregeneration,drug delivery,sutures

NaturalMaterials
Naturalmaterialsareoftensimilar,ifnotidenticaltomacromolecular materialsthebiologicalenvironmentcanrecognizeandprocessthrough metabolicpathways Naturalmaterialscanfunctionbiologicallyatthemolecularlevel,notjust macroscopiclevel Inflammatoryresponseinvokedbysyntheticmaterialissuppressedwith naturalmaterials Naturalpolymerscanoftenbedegradedbynaturallyoccurringenzymes leadingtothematerialbeingmetabolizedbyphysiologicalmechanisms
Isthisadisadvantage?Perhapsincertainapplications,butinothersitcanbequite advantageous.Forexample,implantsdesignedtodeliveraspecificfunctionfora temporaryamountoftime. Crosslinksmakelessdegradable

NaturalMaterials
Disadvantagesofnaturalmaterials:
Similaritytobiologicalsubstancesofteninvokesaimmunogenicresponse (thisisparticularlyaproblemforproteins).Bodysimmunesystem recognizesforeignmaterialandattemptstodestroy. Highdegreeofvariabilityinnaturalmaterialsderivedfromanimalsources Structurallymorecomplexthantraditionalmaterials;manipulationmore elaborateandcomplicated Limitedprocessingroutesinmanycases

NaturalPolymers:StructureandFunction
Whatstheconnectionbetweenbodilytissuesandpolymers? FourPrincipleTissueTypes
Epithelial linessurfacesandcavities;protectsstructures,fluidtransport Connective fibrous,loadbearing Muscle contractilefilaments;externalandinternallocomotion Nervous muscleandmentalactivity

Principletissuesarelargelycomposedbythreetypesof biopolymers:
Proteins chainsofaminoacids(silk,collagen,elastin,fibrin) Polysaccharides chainsofsugar(chitin,glycosaminoglycans) Polynucleotides chainsofnucleotides(DNA,RNA)

NaturalPolymers:StructureandFunction
Iftheconstituentmoleculesinnaturaltissuearesimilar,what influencesthematerialproperties?
Molecularconfiguration 29differenttypesofcollagenhavebeen identifiedwithdifferentcrosslinksandstructuralhierarchies Composition cartilagehas30xmorepolysaccharidesthanligament Organization cartilageisisotropic,ligamenthasapreferreddirection

OverridingPrinciple:Natureadaptsstructuretoperformaspecificfunction

NaturalPolymers:StructureandFunction
Thestructuralelementsofthehumanbodyarethecellsand theextracellularmatrix(ECM) thecellssecrete Inbiomaterials,wegenerallyusenaturalpolymersfromthe ECMofconnectivetissues(e.g.tendon,skin,ligament,blood vessels,cartilage,bone

NaturalPolymers:StructureandFunction

NaturalPolymers Proteins
Protein Structure:
Polymer:chainsofaminoacid Bonding:covalentpeptidebonds Hydrophoblic core,hydrophilicexteriorinteractswithaqueous environment Proteinfoldinaspecificmannerforaspecificfunction(most complicatedmacromoleculesinthehumanbody)

Function
Actasenzymes(assemble/disassembleothermolecules) Alsoservetoprovidestructuralstability(connectivetissue)

Collagen
Collagenisthemostabundantproteinpresentinthehumanbodybeing themajorcomponentofskinandothermusculoskeletaltissues. Collagenisarodtypepolymernearly300 nmlongwithamolecular weightof300,000. Morethantwentytwodifferenttypesofcollagenidentifiedsofarinthe humanbody,withthemostcommonbeingTypeIIV. TypeIcollagenisthesinglemostabundantproteinpresentinmammals andisthemostthoroughlystudiedprotein. TypeIcollageniscomposedofthreepolypeptidesubunitswithsimilar aminoacidcompositions.Eachpolypeptideiscomposedofabout1050 aminoacids,containingapproximately33%glycine,25%proline and25% hydroxyproline witharelativeabundanceoflysine.

Collagen

CollagenTypes
Type Fibrillar Collagens I 300nmlongfibrils Skin,tendon,bone, ligaments,dentin, interstitialtissues Cartilage,vitreoushumor Skin,muscle,bloodvessels SimilartotypeI;alsocell cultures,fetaltissues StructuralFeatures RepresentativeTissues

II III V

300nmlongfibrils 300nmlongfibrils;often withtypeI 390nmlongfibrilswith globularNterminal domain;oftenwithtypeI

SOURCE:K.Kuhn,1987,inR.Mayne andR.Burgeson,eds.,Structureand FunctionofCollagenTypes,AcademicPress,p.2;M.vanderRestandR. Garrone,1991,FASEBJ.5:2814.

StructuralOrderinCollagen
Structuralorderincollagen occursatseveraldiscretelevels Primarystructure sequence ofaminoacids Secondarystructure local configurationofpolypeptide chainsthatresultsfrom satisfactionofstereochemical anglesandhydrogenbonding betweenpeptideresidues Tertiary global configuarations ofpolypeptide chains.triplehelicalcollagen molecule Quaternarydenotesrepeating supramolecular unitstructure comprisingseveralmolecules packedintoaspecificlattice. Basicunitofthemicrofibril

NaturalPolymers Proteins

NaturalPolymers Proteins

Collagenundergoesenzymatic degradationwithinthebodyvia enzymes,suchascollagenases andmetalloproteinases,to yieldthecorrespondingamino acids. Duetotheirenzymatic degradability,uniquephysico chemical,mechanicaland biologicalpropertiescollagen hasbeenextensively investigatedforbiomedical applications. Collagenismostlysolublein acidicaqueoussolutionsand canbeprocessedintodifferent formssuchassheets,tubes, sponges,foams,nanofibrous matrices,powders,fleeces, injectableviscoussolutionsand dispersions. Studieshavealsoshownthat thedegradationrateofcollagen usedforbiomedical applicationscanbesignificantly alteredbyenzymaticpre treatmentorcrosslinkingusing variouscrosslinkingagents.

B.Ratner,A.Hoffman,F.Schoen,andJ.Lemons:BiomaterialsScience, 2ndedition(SanDiego:ElsevierAcademicPress.2004).134.

NaturalPolymers Polysaccharides

NaturalPolymers Polysaccharides

NaturalPolymers Polysaccharides

B.Ratner,A.Hoffman,F.Schoen,andJ.Lemons:BiomaterialsScience, 2ndedition(SanDiego:ElsevierAcademicPress.2004).135.

NaturalPolymers Polysaccharides