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MaterialsTodayVolume17,Number2March2014 UNCOVERED

Uncovered

Calcium phosphate blossom for bone tissue engineering

3D printing scaffolds

Vladimir K. Popov

1,

* , Vladimir S. Komlev

2

and Boris N. Chichkov

1,3

1InstituteofLaserandInformationTechnologies,RussianAcademy ofSciences,Moscow,Russia

2A.A.BaikovInstituteofMetallurgyandMaterialsScience,Russian AcademyofSciences,Moscow,Russia

3LaserZentrumHannovere.V.,Hannover,Germany

Theeffectivemedicaltreatmentofcraniofacialandskeletalbone defectsduetotrauma,tumorremovalorcongenitalabnormalitiesis a greatchallenge for reconstructivesurgery. Biocompatible syn- thetic grafts and/or tissue engineering constructions based on cell-seededscaffoldsarethekeyelementsrequiredforsuccess.For effectivetreatment,boththeinitialmaterialsandthescaffolditself mustmeetthe‘‘goldenstandard’’–autologousbone.Thismeans thattheymustbebiocompatible(possessloworpreferably‘‘zero’’

cytotoxicity),bioactive(initiateeffectiveosteogenesisandneovas- cularization),bioresorbable(dissolveordegradewithinthebody withpredetermined rate andby controllablemanner)and have demandingmechanicalcharacteristics.Theparticularrequirement is that scaffolds must comprise interconnected porosity with specific surface functionalization of internal domains ensuring intensive osteoprogenitor cell attachment, proliferation and ingrowth,aswellasnutritionandwasteexcretion.

There are a wide variety of materials (ceramics, bioglasses, polymersand their combinations) and methods (saltleaching, gasfoaming, sprayand freeze drying, etc.)that can beusedto achievethistarget.TheapplicationofdifferentversionsofRapid PrototypingorAdditiveManufacturing(layer-by-layerfabrication ofsolidreplicasofthree-dimensionalcomputermodellingofthe requiredobjects)techniquesfortheeffectiveproductionofbone tissue engineeringscaffolds based onbioactive ceramics is cur- rently considered one of the most advanced and attractive approaches.Thesetechniquesenablefast,reliableandreproduci- ble fabrication of custom-designed matrixes of almost any demandedshapeand internalstructureusingCAD/CAM(Com- puter-Aided Design/Computer-Aided Manufacturing) data. 3D- printing, where a liquid ‘‘ink’’ is binds together contours and layersofpowderaccordingtoaslicedvirtualmodel,unambigu- ouslypresentsthemostpromisingandcost-effectivetechnology forR&Dofnewbiomedicaldevices.

Overthelastfewdecades,variouscalciumphosphates(hydro- xyapatite,b-tricalciumphosphate,etc.)arewidelyusedasbone substitute materials. Representing mineral content of natural bone, these components provide the intrinsic strength to the implants and functionalscaffolding devices that areneededto sustainphysiologicallyappliedloads.Thebiodegradationrateof calciumphosphates(CP)canbeadjusted,corresponding tothe bone regeneration process, by the alteration of their chemical composition,crystallinity,andsurfacemorphology.

Thecomplexityofnaturalbonepropertieslimitsthecreationof optimal materials and fabrication techniques forideal custom- designed scaffoldsrequired forguided bonetissue engineering.

However, we believe that this problem can be solved via a 3D-printingmethodologyplatform, usingacombinationofdif- ferent CP powders, which could be selectively solidified with variousbinders.

*Correspondingauthor:Popov,V.K.(popov@laser.ru)

96 1369-7021/06ß2014ElsevierLtd.Open access under CC BY-NC-ND license.http://dx.doi.org/10.1016/j.mattod.2014.01.015

(2)

Themainconceptofourworkisbasedonthechemicalinter- actionbetweeninitialcalciumphosphatepowders,e.g.tricalcium phosphate(TCP)andprintingfluid(‘‘ink’’).ItisknownthatTCP canreactwithphosphoricacidasbonecement,formingdicalcium hydrogen phosphate and dicalcium pyrophosphate, which are also bioresorbable calcium phosphates. Thus, the setting and solidification processesduring3D-printing relyontwo typesof interaction:acid–basereactionswiththe formationofaneutral compoundorthehydrolysisreactionofthemetastablephosphate resultinginanadhesiveeffectbetweenparticles.Themainfinal phasesofthe3Dproductareapatiteordicalciumphosphateand dicalcium phosphate dihydrate. To this end, the chemicaland phasecompositionofthe3Dprintedscaffoldcanbeadjustedto controlitsbiodegradationrateandthespecificionrelease/absorp- tionprocessintothesurroundingtissue.Itcanbedonebysoaking the scaffold in solution (Simulation Body Fluid, Dulbecco’s ModifiedEagleMedium,etc.)withacontrolledpHandtempera- tureforapredeterminedtime.Moreover,thisfinalprocedurecan alsoimprovebothmechanicalintegrityandtheosteointegration propertiesofthestructure.

Thisissue’scoverimageshowsthe‘‘blossom-like’’microstruc- tureofbioceramicscaffolds,3D-printedfromfine(ca.40–60mm) tricalciumphosphatepowderusingphosphoricacid-basedadhe- sive‘‘ink’’andsoakedafterwardsinaqueoussodiumacetatesolu- tionfor24hat808C(intermediatephase–dicalciumphosphate dihydrate).In thisstudy, various3D-printedscaffoldsbased on

octacalciumphosphatewereprovidedforbiologicaltestsinvivo.

Weexpectedthat asignificantimprovementinmaterialperfor- mancewillprovidebetterimplantintegrationwiththehosttissue duringtheinitialpost-operativeperiodanditscompletesubstitu- tionwithnewlyformedboneinthelongrun.

Finally,webelievethatfurtherdevelopmentofthismethodol- ogyshouldleadtotheproductionofnew,advancedbiomedical devicesensuringhighquality,reliability,sustainabilityandcost- effectivelevelofmedicalassistanceintherapyandsurgeryasso- ciatedwithbonefracturesanddiseases.

Acknowledgments

ThisworkwassupportedbytheRussianFoundationforBasicResearch (grantnos.13-02-12041and13-03-12021)andGovernmentoftheRussian Federation(contractno.14.B25.31.0019).

MaterialsTodayVolume17,Number2March2014 UNCOVERED

This year’s cover competition is brought to you in associationwithZEISS.Astheworld’sonlymanufac- tureroflight,X-rayandelectronmicroscopes,ZEISS offers tailor-made microscopesystemsfor materials research,academiaandindustry.

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