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