1he overall goal of Lhls mulLldlsclpllnary research pro[ecL supporLed by Lhe naLlonal Sclence

loundaLlon lronLlers of lnLegraLlve 8lologlcal 8esearch program ls Lo furLher advance our

undersLandlng of selfassembly durlng Lhe organlzaLlon of cells and Llssues lnLo funcLlonal organ
modules
1he Lwo developmenLal processes wlLh common and dlsLlncL
feaLures Lo be lnvesLlgaLed ln deLall ln Lhe pro[ecL fuslon of
cardlac cushlons durlng Lhe formaLlon of cardlac chambers (lefL)
and Lhe appearance of llmb buds Lhe precursors of Lhe llmbs
(rlghL) (1he lmages refer Lo chlcken embryos)

1he sLraLegy of our mulLldlsclpllnary approach for addresslng Lhls fundamenLal blologlcal problem of
Lremendous complexlLy ls based on Lhe recognlLlon LhaL alLhough morphogeneLlc processes are
under sLrlcL geneLlc conLrol genes do noL creaLe shapes and forms physlcal mechanlsms and
processes do Cur efforLs Lo reveal Lhe prlnclples of cellular organlzaLlon wlll focus on Lwo speclflc
apparenLly slmllar developmenLal phenomena Lhe formaLlon of cardlac cushlons and llmb buds 1he
ma[or blophyslcal framework wlLhln whlch Lhese processes wlll be sLudled ls Llssue llquldlLy Lhe ln
vlLro and ln vlvodemonsLraLed concepL accordlng Lo whlch embryonlc Llssues mlmlc Lhe behavlor of
llqulds 1he molecular basls of Lhls behavlor wlll be lnvesLlgaLed Lhrough geneLlc manlpulaLlons and
Lhe lnLerplay beLween blomolecular and blophyslcal deLermlnanLs wlll be explored by Lhe
comblnaLlon of expetlmeotol and moJelloq tecbolpoes 1he knowledge galned from Lhese sLudles
wlll serve as blologlcal valldaLlon for new meLhods for bulldlng Lhreedlmenslonal llvlng sLrucLures of
speclflc geomeLrles 1he proposed research wlll Lhus have boLh baslc and applled sclence
componenLs 1he former wlll be based on key sclenLlflc concepLs underlylng early developmenL cell
exLracellular maLrlx (LCM) lnLeracLlons eplLhellal
mesenchymal LransformaLlon and physlcal mechanlsms of
morphogenesls 1he laLLer wlll rely on Lhe Lechnology of
bloprlnLlng speclflcally our cusLombullL bloprlnLers
operaLlng wlLh blolnk parLlcles composed of spheroldal
cell aggregaLes and blopaper made of blocompaLlble
LCMconLalnlng hydrogels
SchemaLlcs of bulldlng a Lubular organ module by bloprlnLlng 1he blue sheeLs represenL Lhe
blopaper or scaffold gel 1he gel and Lhe hlsLoLyplcal spherlcal blolnk parLlcles are deposlLed/prlnLed
layerbylayer
1he ouLllned program wlll be carrled ouL by Lhe lnLegraLlon of developmenLal cell and molecular
blology wlLh Lhe physlcal and englneerlng sclences modellng wlLh experlmenLs and research wlLh
educaLlon
ln Lhe course of Lhls pro[ecL we anLlclpaLe LhaL we wlll dlscover new prlnclples of mulLlcellular self
organlzaLlon (morphogenesls organogenesls) whlch ln Lurn wlll enable us Lo develop funcLlonal
blologlcal sLrucLures for baslc sclence purposes (eg ln vlLro sLudles of mechanlsms of developmenL
and Lumor formaLlon) and appllcaLlons such as LargeLed drug LesLlng and dellvery and organ
(module) replacemenL
uue Lo lLs sLrongly crossdlsclpllnary characLer our research program wlll provlde excellenL Lralnlng
grounds for sLudenLs who wlll be faclng challenges awalLlng educaLors and sclenLlsLs ln Lhe llfe
sclences enLerlng Lhe 21sL cenLury workplace Cur educaLlonal acLlvlLy wlll be cenLered on flve ma[or
componenLs currlculum developmenL sLudenL research programs sLudenL/educaLor forums
speclal summer programs and ouLreach
WhaL lf Lhe Lens of Lhousands of people walLlng for organ LransplanLs ln Lhe unlLed SLaLes dldnL
have Lo walL? WhaL lf burn vlcLlms could replace Lhelr scars wlLh skln LhaL was lndlsLlngulshable from
Lhelr own? WhaL lf an ampuLee could replace an enLlre llmb wlLh one LhaL felL looked and behaved
exacLly as Lhe orlglnal?
ln whaL could be Lhe flrsL sLep Loward human lmmorLallLy sclenLlsLs say Lheyve found a way Lo do
all of Lhese Lhlngs and more wlLh Lhe use of a Lechnology found ln many Amerlcan homes an lnk[eL
prlnLer
8esearchers around Lhe world say LhaL by uslng Lhe Lechnology Lhey can acLually prlnL llvlng
human Llssue and one day wlll be able Lo prlnL enLlre organs
1he promlse of Llssue englneerlng and Lhe promlse of organ prlnLlng ls very clear We wanL Lo prlnL
llvlng Lhreedlmenslonal human organs ur vladlmlr Mlronov sald 1haLs our goal and LhaLs our
mlsslon
Whats |n a Name?
1hough Lhe fleld ls young lL already has a mulLlLude of names
Some people call Lhls bloprlnLlng Some people call Lhls organ prlnLlng Some people call Lhls
compuLeralded Llssue englneerlng Some people call Lhls blomanufacLurlng sald Mlronov
assoclaLe professor aL Lhe Medlcal unlverslLy of SouLh Carollna and one of Lhe leadlng researchers ln
Lhe fleld
lL looks llke every new guy who [olns lnLo Lhls fleld Lrles Lo lnLroduce a new Lerm
1he commonly used Lerm ls organ prlnLlng and ls slmple ln concepL buL lncredlbly complex and
challenglng ln lLs execuLlon
WhaL we do ls we modlfy lLs a regular lnk[eL prlnLer buL we do noL use Lhe paperfeed
mechanlsm so baslcally we [usL have a carLrldge movlng back and forLh and where Lhe paper goes
we puL a peLrl dlsh explalned 1homas 8oland an assoclaLe professor aL Clemson unlverslLy
8oland says LhaL Lhere ls some llquld ln Lhe dlsh and LhaL ln place of lnk carLrldges are carLrldges
fllled wlLh cells and a crossllnker
1he crossllnker ls a chemlcal LhaL causes Lhe llquld ln Lhe peLrl dlsh Lo gel glvlng Lhe prlnLer a sofL
buL solld !ellCllke surface Lo prlnL Lhe cells on
1he process can be repeaLed over and over addlng llquld gelllng lL prlnLlng more cells and bulldlng
layer upon layer creaLlng Lhree dlmenslons
|m|tat|ons and Cbstac|es
8lghL now sclenLlsLs are llmlLed Lo a maxlmum of abouL 2 lnches of Lhlckness Crosslng LhaL
Lhreshold presenLs one of Lhe Lechnlques flrsL blg hurdles
When you prlnL someLhlng very Lhlck Lhe cells on Lhe lnslde wlll dle Lheres no nuLrlenLs geLLlng
ln Lhere so we need Lo prlnL channels Lhere and hope LhaL Lhey become blood vessels 8oland
sald
ln any glven human organ Lhere are blood vessels feedlng Lhe organ Lo keep lL allve and worklng
properly WlLhouL Lhe blood vessels Lhe organ wlll dle and LhaLs Lhe problem faclng researchers ln
bulldlng an organ for use ln a human Pow do you geL Lhe prlnLed organ Lo grow and malnLaln blood
vessels?
AlLhough Lhere are a few compeLlng schools of LhoughL on Lhls llke mosL Lhlngs ln sclence work
lngenulLy and maybe a llLLle money are whaL researchers say wlll puL prlnLed organs ln llve humans
ln Lhe fuLure maybe 30 years from now we wlll be able Lo make very complex organs and
bones and very complex Llssues he sald
And when Lhey can Lhey wonL have Lo worry abouL re[ecLlon because Lhe replacemenL parL wlll be
caLered Lo Lhe lndlvldual recelvlng lL
A8S18AC1
1lssue englneerlng Lechnology promlses Lo solve Lhe organ LransplanLaLlon crlsls Powever
assembly of vascularlzed 3u sofL organs remalns a blg challenge Crgan prlnLlng whlch we
deflne as compuLeralded [eLbased 3u Llssueenglneerlng of llvlng human organs offers a
posslble soluLlon Crgan prlnLlng lnvolves Lhree sequenLlal sLeps preprocesslng or
developmenL of blueprlnLs for organs processlng or acLual organ prlnLlng and
posLprocesslng or organ condlLlonlng and acceleraLed organ maLuraLlon A cell prlnLer LhaL
can prlnL gels slngle cells and cell aggregaLes has been developed Layerbylayer
sequenLlally placed and solldlfled Lhln layers of a Lhermoreverslble gel could serve as
prlnLlng paper ComblnaLlon of an englneerlng approach wlLh Lhe developmenLal blology
concepL of embryonlc Llssue fluldlLy enables Lhe creaLlon of a new rapld proLoLyplng 3u
organ prlnLlng Lechnology whlch wlll dramaLlcally acceleraLe and opLlmlze Llssue and organ
assembly

9|nt|ng Cgans |n Ink[et 9|nte Can Save 1wo |ves a M|nute
AnLhony ALalas sLaLeofLhearL lab grows human organs muscles blood vessels bladders
and more ln Lhls vldeo he shows fooLage of hls bloenglneers worklng wlLh advanced
Lechnology lncludlng a machlne LhaL prlnLs human Llssue


D Meco|as Comments


ur Aubrey de Crey one of Lhe leadlng anLl aglng blologlsLs has long sLaLed LhaL he belleves Lhe way
we wlll exLend our llfespan beyond 120 years old ls Lo replace Lhe parLs LhaL wear ouL
1haL ls one of Lhe reasons why l flnd Lhls llne of research so appeallng because lL seems Lo be a real
world lmplemenLaLlon of ur de Creys sLraLegy
Cf course Lhls Lechnology can also be used for organ replacemenL noL due Lo aglng As of lebruary
10 2010 Lhere were over 103600 people walLlng for an organ donaLlon ln Lhe unlLed SLaLes
Powever from !anuary Lo november 2009 [usL over 26000 organ LransplanLs Look place
1he number of people ln need of organ LransplanLs ls slmply rlslng fasLer Lhan Lhe number of
avallable donors and as a resulL 19 people dle every day due Lo Lhls shorLage
So lL would be noLhlng shorL of mlraculous lf we could one day replace vlrLually every organ or Llssue
ln paLlenLs bodles wlLh young prlsLlne organs as Lhey age or become dlseases or ln[ured
8ecenLly sLeps Loward achlevlng Lhls goal have advanced greaLly lncludlng Lhe amazlng work belng
conducLed aL ur AnLhony ALalas Wake loresL lnsLlLuLe for 8egeneraLlve Medlclne
abGown Cgans and 1|ssues ae nee
CurrenLly ur ALala and hls colleagues are worklng on developlng organs and Llssues for vlrLually
every parL of Lhe human body 1hey were Lhe flrsL Lo creaLe human bladders ln Lhe lab and
successfully lmplanL Lhem ln paLlenLs
1hey are also ln Lhe process of englneerlng a human ear and developlng Lechnology Lo prlnL skln
dlrecLly on burns uslng an ordlnary lnk[eL prlnLer!
1he lnsLlLuLe has also ldenLlfled a new Lype of nonconLroverslal sLem cells LhaL come from amnloLlc
fluld and placenLa
AdulL sLem cells (as opposed Lo embryonlc sLem cells whlch are aL Lhe hearL of Lhe sLem cell
conLroversy) are a Lruly exclLlng parL of Lhe fuLure of medlclne especlally anLlaglng medlclne
As you age your sLem cells dlmlnlsh ln quallLy and quanLlLy so [usL when you requlre sLrong sLem
cells Lhe mosL youre becomlng deflclenL Pence your organs and Llssues evenLually wear ouL and
need Lo be resLored or replaced
WhaL makes sLem cells so speclal ls Lhelr poLenLlal Lo develop lnLo many dlfferenL cell Lypes When a
sLem cell dlvldes lL elLher becomes anoLher Lype of cell such as a muscle cell or braln cell or lL
remalns a sLem cell lurLher Lhese cells acL as an lnLernal repalr sysLem ln many Lypes of Llssues
dlvldlng a seemlngly lnflnlLe number of Llmes Lo replenlsh oLher cells
1he new Lype of sLem cells ldenLlfled by Wake loresL sclenLlsLs can be used Lo form blood vessel
bone llver muscle and oLher Lypes of Llssues and Lhey say a bank of 100000 speclmens could
poLenLlally provlde 99 percenL of Lhe uS populaLlon wlLh a geneLlc maLch for LransplanLaLlon
noL only are Lhese sLem cells easlly obLalnable buL Lhey can be grown ln large quanLlLles because
Lhey Lyplcally double every 36 hours
egeneat|ve Med|c|ne at |ts I|nest
CurrenLly researchers aL Lhe lnsLlLuLe are also worklng Lo grow more Lhan 22 dlfferenL Lypes of
organs and Llssues ln Lhe lab and are developlng cell Lheraples for dlseases such as dlabeLes and
muscular dysLrophy
?our body already has an amazlng ablllLy Lo regeneraLe such as heallng a skln wound or broken
bone lLs also Lrue for organs such as your llver
8lghL now sclenLlsLs can lmplanL speclal smarL blomaLerlals Lo form a maLrlx Lo help your bodys
Llssues rebulld Lhemselves buL lL only works for small areas Lyplcally 1 cenLlmeLer or less 1hese
new advances wlll make lL posslble Lo noL only replace enLlre organs buL also Lo repalr much larger
areas
Already one man was able Lo regeneraLe a losL flngerLlpuslng a speclal powder subsLance called
exLracellular maLrlx a mlx of proLeln and connecLlve Llssue surgeons use Lo repalr Lendons lL
slgnals your body Lo sLarL Lhe process of Llssue regrowLh and ln [usL four weeks hls flngerLlp grew
back compleLely
SclenLlsLs are also uslng paLlenLs own cells Lo grow organs ln Lhe lab as Lheres llLLle rlsk of re[ecLlon
when uslng your own adulL sLem cells 1hls means youre less llkely Lo need dangerous
lmmunosuppresslve drugs LhaL are common wlLh some LreaLmenLs
When l served as Lhe kldney LransplanL coordlnaLor for Lhe unlverslLy of llllnols prlor Lo sLarLlng
medlcal school ln 1978 lL was clear LhaL Lhe ablllLy Lo produce organs and noL have Lo puL people
on walLlng llsLs would be an amazlng accompllshmenL of modern medlclne
lL seems we are now closer Lo Lhls goal Lhan ever before