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Page 1: Controll ed multiple growth factor d elivery from bone ... · Michigan, Ann A ve Research Cente suarez@gmail.com l t , l . . , , may b scaffo biolog Figure TCP s contin like na Figure

Ssoarebrethinpfaarem(mgcrebinlugth5bsmgMimainS(mispsccwAEmrethinfedccRβrewwrhdDgdhimsSindp

Statement of Purpimple mechanism

osteogenic growthangiogenesis playselease of an angi

bone formation. Helevant approachehat mineral coatincorporation and

phosphate (β-TCPfabrication (SFF) approach. Mineral ecombinant huma

modular, mineral-mBMP2) solution

growth factor. Theculture medium anelease of both gro

biological activityntramuscular sheeumborum and coll

growth factor, rhVhe combination o

50μg mBMP2. Thblood vessel ingrohowed an increa

manner in groups rgrowth factors. Methods: β-TCP smage-based desig

achieve scaffolds nterconnected por

Scaffolds were incmSBF) for periods a solution simi

plasma. The minecanning electron m

conducted using 12

carboxyfluoresceinwere sequentially After binding, β-TEagle’s medium (Dmedia were collecteleased growth fache released mediuntensity for mBM

female sheep weredelivering differencombination from consisted of mineraResults: Our resultβ-TCP scaffolds (esults in binding o

we showed sustainwith VEGF releashVEGF in vivo in

dose dependent maDiscussion: In thisgrowth factor releadouble dipping prohighly adaptable camplanted in vivo, caffolds.

Significance: This n which a controll

device as a thin surphysical properties

Controlle

pose: The objecti for release of two

h factor, from a ss an important roiogenic and osteo

However, there remes for dual growthings could be urelease of multip

P) scaffolds weretechniques and mcoated β-TCP sc

n vascular endothbinding version

ns for one hour eace dual release profind simulated bodyowth factors for ovy of the growth p model. Scaffoldlected at 2 and 4 w

VEGF, were assessof the different dohe samples collectowth using vonWiase in blood vessreleasing either rh

scaffolds were fabgn and 3D printi

with controlled res with a 40% cubated at 37 ˚C

ds of 7 days underilar in ionic compral formed on themicroscopy (SEM

25I-labeled rhVEGFn labeled mBMP2

dipped in solutioTCP granules wereDMEM) at 37oC. ted and replaced ctor was determine

um for rhVEGF reMP2. For our in ve used. The experint dosages of rhVE

mineral coated βal coated scaffoldsts demonstrate tha(Figure 1), and tof both rhVEGF aned dual release osing more rapidly nduced an increaseanner (Figure 4). s study, we develoase of an angiogeniocess. The mineral arrier to bind and rrhVEGF increased

approach demonsable biologics carrrface coating, with of the device. Thi

ed multiple gr1Suarez-Gon

3AO Foun

ives of this study o growth factors, scaffold material. ole in bone regenogenic growth facmains a need for h factor release.

used as a platforple growth factors fabricated using

mineral coated usaffolds were sequ

helial growth factoof bone morpho

ch to allow for incfile was characterizy fluid (SBF), and ver more than 60

factors was chads were implanted weeks. Different dsed (0.5, 1, 5, andosages of rhVEGted at 2 weeks willebrand factor stsel ingrowth in ahVEGF alone or th

bricated by SFF fabing techniques warchitecture: sqvolume void fr

in modified simur continuous rotatiposition and teme material was ch

M). Binding and reF (Perkin Elmer; . Mineral coated

ons of either rhVe incubated in DuAt specific time pwith fresh mediumed by measuring tlease; or by measuvivo studies, 10 Hmental group con

EGF, mBMP-2 froβ-TCP scaffolds. Ts with no growth faat we could form mthat the “double and mBMP2 (Figuof rhVEGF and m

than mBMP2. Se in the number of

ped a simple approic and osteogenic coating served as

release rhVEGF and blood vessel ingr

strates a “modular rier is integrated in

hout negatively impis type of modular

owth factor dnzalez, D; 2Diggs,

1University of2University of

ndation Collaboratidarilis.

were to develop aan angiogenic andIt is known that

neration, and thatctors can enhance

simple, clinicallyWe hypothesized

rm for controlleds. Beta tricalciumg solid free formsing a biomimeticuentially dipped inor (rhVEGF) and agenetic protein 2orporation of eachzed in vitro in celshowed sustaineddays. The in vivoaracterized in anin the longissimus

dosages of a singled 10μg) as well as

GF combined withwere evaluated fortaining (vWF) anda dose dependenhe combination of

brication. In shortwere employed toquare, orthogonaraction (porosity)ulated body fluidson. Modified SBF

mperature to bloodharacterized usinglease studies wereBoston, MA), andd β-TCP scaffolds

VEGF or mBMP2ulbecco’s modifiedpoints, the releasem. The amount ofthe radioactivity ofuring fluorescenceHampshire mature

nsisted of scaffoldsom mineral, or theThe control groupfactor. mineral coatings on

dipping” processure 2). In addition

mBMP2 (Figure 3)Scaffolds releasingf blood vessels in a

oach for dual factor based on a a simple and

nd mBMP2. Whenrowth in the

design” approach,nto the structural pacting the bulk r design approach

elivery from bA; 1Lee, JS; 2Holl

f Wisconsin, Madif Michigan, Ann Aive Research [email protected]

a d t t e y d d

m m c n a 2 h l d o n s e s h r d t f

t, o l . s F d g e d s . d e f f e e s e p

n s

n, , g a

n

,

may bscaffobiolog

FigureTCP scontinlike na

Figuredippinamounsignifi

FigureDMEMgrowthions is

FigurearrowsvesselrhVEGPositivblood pores condit

a)

bone tissue enlister, SJ; 1,3Murphison, WI

Arbor, MI er, Davos, Switzerm

be particularly usefolds, in which theregical properties.

e 1: a) β-TCP scaffscaffolds in mSBF nuous coating. d) Tanostructure chara

e 2: a) Dual growthng of scaffolds in rnt of rhVEGF bouicantly changed du

e 3: Dual release oM. Release was suh factors was slows likely causing the

e 4: rhVEGF releas) 2 weeks after imls within sections oGF; b) 0.5μg rhVEve vWF staining isvessel. e) Quantifof the scaffold. *ption. Scale bars = 1

gineering scafhy, WL

rland

ful for design of boe is a clear need fo

ffold fabricated via

for 7 days resulteThe morphology ofacteristic of hydrox

h factor binding wrhVEGF initially, fnd to the scaffoldsuring the second d

of rhVEGF and mBustained for over 2wer compared to De slower release of

se enhanced bloodmplantation. a-d) vof implanted β-TCEGF; c) 1.0μg rhVs brown, and circufication of the nump < 0.009 relative t100μm.

b)

ffolds

one tissue engineeor optimized physi

a SFF. b-c) Incubatd in the formationf the mineral displxyapatite.

was obtained after tfollowed by mBMs after the first dip

dipping step.

BMP2 in a) SBF an months. In SBF thMEM. The re-precf growth factors.

d vessel ingrowth (vWF immunostainiCP scaffolds releasi

EGF; d) 10μg rhVular vWF staining rmber of blood vesseto the NO Growth

ering cal and

tion of β-

n of a layed a plate

the sequential

MP2. b) The ping was not

nd b) he release of cipitation of

(black ing of blood ing a) No

VEGF. represents a els within the factor

Poster No. 0656 • ORS 2012 Annual Meeting

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