ShaochenChen,PhDProfessorofNanoEngineeringandBioengineering

Co-Director,BiomaterialsandTissueEngineeringCenter(BMTec)Ins>tuteofEngineeringinMedicine(IEM)

ClinicalandTransla>onalResearchIns>tute(CTRI)UniversityofCalifornia,SanDiego

RapidScanningless3DPrin2ng:Vision,Status,andResearchNeeds

Scanning3DPrin2ngTechnologies

Inject-based Extrusion-based Light-assisted

MurphySVandAtalaA.NatBiotechnol.2014

UVlaser

Mapilli,Lu,Chen,Roy,J.Biomed.Mat.Research(2005)

Scanningless3DPrin2ngTechnologies

Zhang,Qu,Soman,Hribar,Lee,Chen,He,AdvancedMaterials,2012.

Lu,Mapili,Chen,andRoy,J.BiomedicalMaterialsResearch,2006

Layer-by-layerProjec>onPrin>ng Dynamic,Con>nuousProjec>onPrin>ng

DLP Printing of Vascular Grafts

Melchiorri,A.J.etal(JohnFisheratUM),AdvHealthcareMater,2015.

Complex3DArraywithSmoothSidewalls

Zhang,Qu,Soman,Hribar,Lee,Chen,He,AdvancedMaterials,24(31),4266-4270(2012).

Pyramid Spiral Dome Flower

Con>nuousprin>ngiskeytoeliminatear>ficialinterfacesbetweendropsandlayersinnozzle-based3Dprin>ng.

Continuous Liquid Interface Production

Tumbleston,J.R.etal(JoeDeSimoneatUNC)),Science,2015.

MaterialsUsedfor3DPrin2ng

•  Poly(ethyleneglycol)Diacrylate(PEGDA)–  Photo-crosslinkable–  Tunablemechanicalproper>es–  Nontoxic,non-immunogenic–  Canbechemicallymodified(i.e.,RGD,heparansulfates)

•  Gela2nMethacrylate(GelMA)–  Biodegradable–  Celladhesive

•  HyaluronicAcid(HA)–  Biodegradable–  Celladhesiveifcovalentlyfunc>onalizedwithacell-adhesiveprotein(e.g.lamininusingEDC-NHS)

Cell Alignment on Stiffness-Patterned Hydrogel Day 6

100um

Day 43hrs Day 2

Patterns

Invitrocellmigra>on.A7R5smoothmusclecellsshowmigra>ontothes>fferregionspa`ernedbythedigitalplasmonicpa`erningmethod.

Fluorescentstainingshowstheirac>n(red)andnuclei(cyan).

Wen,Vincent,Choi,Fuhrmann,Hribar,Chen,Engler,NatureMaterials,13,979-987,2014Hribar,Choi,Ondeck,Engler,Chen,AdvancedFunc?onalMaterials,24,4922-4926,2014

Nanopar2cles-enabled3DDetoxifica2on

Gou,Qu,Zhu,Xiang,Yang,Zhang,Wei,andChen,NatureCommunica?ons,5:3774,2014

Polydiacetylene(PDA)nanopar>cles(green)areinstalledinPEGDAhydrogelmatrix(grey)withliver-mime>c3Dstructurefabricatedby3Dprin>ng.ThePDANPscana`ract,captureandsensetoxins(red),whilethe3Dmatrixwithmodifiedliverlobulestructureallowstoxinstobetrappedefficiently.

Liver-mimic3DDetoxifica2on

Gou,Qu,Zhu,Xiang,Yang,Zhang,Wei,andChen,NatureCommunica?ons,5:3774,2014

3D-printed Artificial Micro-fish

Zhu et al, Advanced Materials, 27, 4411 (2015)

Fish-shapedmicrorobots•  Swiminliquids•  Chemicallypowered•  Magne>callyguided•  Detoxifythetoxins

Inside Cover Image

3D-printed Micro-fish to Remove Toxin

Zhu et al, Advanced Materials, 27, 4411 (2015) Press report by The Wall Street Journal, The Washington Post, Forbes, BBC News, etc

Nano-robots:•  Self-propelled•  Sensing•  Drugdelivery•  Nano-surgery

Cells: hiPSC-HPCs Hydrogel: GelMA

3DBioprin2ngofHumanLiverTissues

MaXetal.PNAS.Vol.113(8),2208-2211,2016

Printed in 1 second

Cells: HUVEC and ADSC Hydrogel: GelMA with HA

Two-StepBioprin2ng

MaXetal.PNAS.Vol.113(8),2208-2211,2016

Printed in 1 second

hiPSC-HPCs HUVEC and ADSC Merge Bright Field

BioprintedHepa2cConstruct

3D reconstruction

MaXetal.PNAS.Vol.113(8),2208-2211,2016

PaQernMaintenancePost-prin2ng

Day

1

Day

3

Day

7

Day

10

hiPSC-HPCs HUVEC and ADSC Merge Bright Field

MaXetal.PNAS.Vol.113(8),2208-2211,2016

Liver-specificGenesandFunc2ons

ALB-albumin;HNF4a-hepatocytenuclearfactor4alphaTTR-transthyre>n;AFP-fetalhepa>cmarkeralpha-fetoprotein

MaXetal.PNAS.Vol.113(8),2208-2211,2016

ExpressionLevelsofKeyEnzymesinDrugTes2ng

•  hiPSC-HPCsin3DtriculturehavethehighestaverageexpressionlevelsofCYPs•  Rifampicin(an>bio>cs)trea>ngledtosignificantincreaseinCYP3A4,2C9,2C19

in3Dtriculture,butnotin2Dor3D-HPConlymodels.

MaXetal.PNAS.Vol.113(8),2208-2211,2016

Summary

Ø  Light-basedscanningless3Dprin>ngapproachesofferarapidprin>ngspeedwithmicroscaleresolu>on.

Ø  BioPrin>ngallowsdirect-writeof3D,novel,biomime>cbiologicalscaffoldswithcontrolofchemical,biological,andmechanicalproper>es:

-porosity,shape,s>ffness,Poissonra>o-chemicalcomposi>on-cellencapsula>on

Ø  Avarietyofbiopolymers(e.g.PEG,GelMA,HA)canbeusedforprecision>ssuemodels(invivoandinvitro)

GapsandResearchNeeds

Ø Mul>plematerialsparallelprin>ng,Ø Mul>plecellscon>nuousprin>ng

Ø  Developviablecollabora>onwithmedicaldoctorandbiologistsØ  Developnovelbiomaterialsfor>ssueengineeringand

regenera>vemedicineØ  Developeffec>vevasculariza>onstrategiestokeepengineered

>ssuesaliveØ  High-throughputmanufacturing

ScienceOutreach:1-secondPhoto

Highschoolstudentsinthehydrogel(pictureswithpermission)

ItalianNa>onalTVProducer Publictalkshowforbioprin>ng