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HEART VALVES
I. INTRODUCTION

1.1. Heart and Heart Valves
It is easily understood that the muscle that we call the heart must continue to pump with adequate force to
pump the blood that the body needs. "Vales" howeer are extremely important to the heart!s efficiency.
"hese delicate structures allow for the efficient flow of blood pro#ressiely forward throu#h the heart!s
chambers$ maximi%in# the efficiency of the heart muscle!s work.
In order to understand the importance of the heart ales there is a summary of the heart #ien below &see
'i#. ($ from www.heartpoint.com)
* "he +i#ht ,trium receies "used blood" from the body. Blood will be pushed throu#h the tricuspid
ale to the
* +i#ht Ventricle$ the chamber which will pump to the lun#s throu#h the -pulmonic ale. to the
* /ulmonary ,rteries proide blood to both lun#s. Blood is circulated throu#h the lun#s where carbon
dioxide is remoed and oxy#en added. It returns throu#h the
* /ulmonary Veins$ which empty into the
* 0eft ,trium$ a chamber that will push the -1itral Vale. open. Blood then passes into the
* 0eft Ventricle. ,lthou#h it doesn!t always look like it in drawin#s done from this an#le$ this is the
lar#est and most important chamber in the heart. It pumps to the rest of the body. ,s it pumps$ the pressure
will close the -mitral ale. and open the -aortic ale.$ with blood passin# throu#h to the
* ,orta$ where it will be deliered to the rest of the body.
'i#. (. "he whole heart. &www.heartpoin.com)

1.2. Causes of Disease on Heart Valves
Conenital !eart disease" /roblems with the heart ales may be present from birth. 'or instance$ so-called
"bicuspid aortic ale"$ bein# of made of two leaflets instead of three$ is often associated with an accelerated
incidence of aortic stenosis that may occur when the patient is in his or her fifties.
R!eu#ati$ !eart disease" 2o called "rheumatic feer.$ inflammatory reaction due to some infections with
the bacteria called "streptococcus" is an example. 3ue to the discoery and use of antibiotics$ rheumatic
feer is far less common than in the past$ particularly in deeloped countries. /roper treatment of strep
infections can preent almost all of the cases of rheumatic heart disease.
'i#. 4 from www.heartpoint.com
Heart atta$%" 2pecific parts of the heart muscle concerned with proper functionin# of the ales can be
in5ured in the course of a heart attack. If there is a tear of part or all of one of the "papillary muscles"$ seere
mitral re#ur#itation can occur rapidly and require emer#ency therapy$ perhaps includin# sur#ery.
&ea%enin of t!e su''ortin stru$tures of t!e !eart" , tear or rupture in mitral ale$ which attach the
ale to its papillary muscle$ can cause substantial leaka#e throu#h the mitral ale. "his may be#in and
pro#ress slowly$ or be quite seere at the onset and require emer#ency sur#ery. 6eakenin# of the walls of the
aorta can occur$ which leads to #radual dilation of the aorta$ which can then lead to substantial leaka#e
throu#h the aortic ale.
&ea%enin of t!e !eart #us$le7 8eart muscle will tend to len#then when it weakens. ,s the chamber
enlar#es$ so too do the holes which the 1itral and "ricuspid ales are desi#ned to coer. ,t some point$
while the ale itself is not diseased$ it simply cannot coer this area$ and -alular re#ur#itation. will be#in
to occur. "his often leads to yet further dilation and enlar#ement of the entricles$ and a "icious cycle"
be#ins to occur.
Infections7 Infection of a heart ale is termed "9ndocarditis" is the term used for infection of a heart ale.
"his is not a common problem$ but it can cause rapid pro#ression of alular disease$ #enerally re#ur#itation$
oer a matter of days to weeks. "his infection requires prompt dia#nosis and treatment$ but may still land up
requirin# ale sur#ery een when cau#ht early.
"here are also specific heart ale problems and other less common causes of ale disease. 1ost common
problems are summari%ed below.
* /roblems with the ,ortic Vale7 ,ortic 2tenosis and ,ortic +e#ur#itation
* /roblems with the 1itral Vale7 1itral 2tenosis and 1itral +e#ur#itation
* /roblems with the /ulmonic and "ricuspid Vales
'i#. :. 8eart$ an oeriew showin# problems. &www.heartpoint. com)
Backward flow of blood is called "re#ur#itation" or "insufficiency"$ and it is termed "1itral +e#ur#itation"
or "1itral Insufficiency" if it occurs throu#h the 1itral Vale. 3ifficulty in openin# the ale is called
"stenosis"$ and if it inoles the ,ortic Vale$ is called ",ortic 2tenosis". &2ee 'i#. :)
1.(. Surer) availa*le for 'ro*le#s +it! t!e Valve
"here are seeral options$ dependin# on the exact type of problem$ patient$ and seerity of the process as
summari%ed in web-site of -heartpoint.com.. 'or instance$ in many cases of mitral re#ur#itation$ a skilled
sur#eon can repair the problems that cause leaka#e without the need for replacement.
;ften$ a ale "rin#" is placed in the orifice that the mitral ale coers to "ti#hten up" the si%e of this area
and allow the ale to coer it more effectiely. "he si%e and shape of the leaflets can be carefully
remodeled$ and torn structures sewn back to#ether. .

2ome mitral and aortic ales simply need to be replaced. "his may not be known until the actual time of
sur#ery$ when a repair for re#ur#itation or a commisurotomy for stenosis can then be seen to be impossible
or ill-adised. "he alular structure is cut out$ and as much of the supportin# structure left as feasible. "he
new ale may be #e$!ani$al or *io'rost!eti$ &'i#ure ()$ and may be done from a standard approach
across the breastbone &"median sternotomy")$ or with some of the new "mini" approaches.
"he patient!s own pulmonic ale may be replaced into the aortic or mitral position$ termed as the +oss
procedure.
1.,. Artifi$ial Valves
"he two main types of ales are "1echanical" and "Bioprosthetic". 1echanical ales hae simply been
deised from scratch$ and are made of metal or similar materials. Bioprosthetic ales are fashioned from
animal or human tissues. &2ee 'i#. <)
'i#. <. ,rtificial ales. &www.heartpoin.com)

-e$!ani$al valves" "here are seeral different arieties$ includin# "bileaflet tiltin# ales" which are
extremely popular and reliable. "iltin# sin#le disc deices are also quite popular. ;lder models included the
"ca#ed-ball" deice and "floatin# discs". "he body does not reco#ni%e these as "forei#n"$ and thus there is
not a fear of re5ection. 1echanical ales are #enerally felt to hae the adanta#e of lastin# the lon#est time.
"heir main disadanta#e compared to other types of ales is the need to take potent blood thinners$ which
decreases the tendency to form clots on their surface.
.io'rost!eti$ valves" "hese use some biolo#ic material in their composition. "hey are all treated$ and do not
carry the risk of re5ection. "reated aortic ales from human cadaers$ treated pi# aortic ales$ and ales
fashioned from the pericardium &the outside linin# of the heart) of cows are all utili%ed. "hese types of ales
do not necessarily require that the patient take blood-thinners$ but #enerally do not last as lon#.
1./. 0ro*le#s in Artifi$ial Valves
"he need and ability to maintain lon#-term anti$oaulation &blood thinnin#) is a ery important factor.
2eeral classes of people may not be #ood candidates to take warfarin &brand name coumadin)$ and therefore
should receie a bioprosthetic ale. "his #roup includes youn# women who wish to become pre#nant.
/eople who hae had preious and sometimes-repeated problems with bleedin# &for example$ frequent
bleedin# from ulcers) are often felt to be better sered with the bioprosthetic ales$ which do not require
anticoa#ulation.
;n the other hand$ for people who are #oin# to need to hae anticoa#ulation anyhow because they hae the
abnormal rhythm known as atrial fibrillation$ usin# a bioprosthetic ale would hae little adanta#e since
they are #oin# to need to take the blood thinner anyhow. "hey will most often receie a mechanical ale to
take adanta#e of its lon#er life.
,s a result$ ale replacements usin# either bioprosthetic or mechanical ales hae the disadanta#es that
are summari%ed by "oshiharu et al &(==>).
* "hey are unable to #row$ repair or remodel
* "hey are both thrombo#enic and susceptible to infection
* "hey hae limited durability and lon#eity
II. RE0ORT
2.1 Alternative Solutions of Valvular Re'la$e#ents
Inesti#ations hae been focused on the techniques of tissue en#ineerin# to create a liin# ale substitute
due to the disadanta#es of alular replacement &'uchs et al 4??(). "he ideal substitute would yield
complete closure and non-obstructieness$ non-thrombo#enicy$ resistance to infection$ inertness to
chemicals. 1oreoer it would be nonhemolytic$ durable and easily and permanently inserted.
;er the last @ years two basic approaches hae been pursued$ i.e. decellulari%ation of xeno#enic ales and
addition of cells or allowin# in#rowth of host cells to occur. Bader et al &(==A) su##ested that tissue-
en#ineered ale made of auto#olous cells and biocompatible scaffold hain# potential to remodel$ repair$
and #row would be faourable option. "hey remoed cells porcine aortic ales by deter#ent cell extraction
usin# "riton. "hey showed remoal of the ori#inal cells while #rossly maintainin# the matrix. 9ndothelial
cells were then isolated from human saphenaus ein expanded in itro$ and seeded onto acellular matrix.
;!Brein et al &(===) su##ested a different decellulari%ation process. , composite heart ale biprosthesis was
prepared by the "2ynerBraft" process after decellulari%ation. "hen the ale composites weer implanted as
pulmonary ale replacements in sheep. "hey reported that all ales weer hemodynamically functional at
explant.
"he second approach inoles traditional tissue en#ineerin#. In this approach autolo#ous cells are
transplanted onto a biode#radable scaffold in the shape of a heart ale &'or instance$ 2odian et al 4???$
"eebken et al 4??4$ 8oerstrup et al 4??4.). "he tissue-en#ineered ale would hae a potential to #row$
remodel and aoid infectious and thrombo#enic complications.
2.2. Tissue Enineerin
"issue en#ineerin# has been rapidly expandin# approach in order to sole the or#an shorta#e problem. It is
an "interdisciplinary field that applies the principles and methods of en#ineerin# and the life sciences toward
the deelopment of biolo#ical substitutes that can restore$ maintain$ or improe tissue function." &'uchs et al
4??(). 1uch pro#ress has been made in the tissue en#ineerin# of structures releant to cardiothoracic
sur#ery$ includin# heart ales$ blood essels$ myocardium$ esopha#us$ and trachea.
;er the last >? years$ transplantation of a wide ariety of tissues$ reconstructie sur#ical techniques$ and
replacement with mechanical deices hae si#nificantly improed patient outcomes &'uchs et al 4??(). "he
first successful or#an transplant was performed by 1urray et al in (=><. 2ince that historic accomplishment$
the field of transplantation has eoled to include kidney$ lier$ split lier$ pancreas$ heart$ lun#$ and small
intestine at hundreds of transplant centers throu#hout the Cnited 2tates. In (=@D$ Barnard performed the first
heart transplant for con#estie heart failure. "hese strides hae been made possible because of the adances
in transplantation biolo#y and immunolo#y leadin# to the deelopment of a ariety of immunosuppressie
a#ents
Cnfortunately$ or#an and tissue transplantation are imperfect solutions because they are limited by a number
of factors. 6orsenin# donor shorta#es result in a discrepancy between the number of patients needin#
transplants and aailable or#ans. ,dditionally$ transplantation recipients must follow lifelon#
immunosuppression re#imens with their increased risks of infection$ tumor deelopment$ and unwanted side
effects. 2ur#ical reconstruction also suffers from a lack of aailable donor tissue and donor site morbidity.
+eplacement with mechanical deices or artificial or#ans is limited by an increased risk of infection and
thromboembolism and finite durability. Because of the aboe shortcomin#s$ the field of tissue en#ineerin#
and selectie cell transplantation was born as a means to replace diseased tissue with liin# tissue that is
"desi#ned and constructed to meet the needs of each indiidual patient" &'uchs et al 4??().
"issue en#ineerin# is defined as "an interdisciplinary field that applies the principles and methods of
en#ineerin# and the life sciences toward the deelopment of biolo#ical substitutes that restore$ maintain$ or
improe tissue function" &'uchs et al 4??().
In (=D>$ Ehick et al were the first to place pancreatic islet cells in semipermeable membranes to improe
#lucose control in diabetes. ;thers created skin substitutes consistin# of fibroblast cells seeded onto colla#en
scaffolds$ which are currently used in clinical practice in the context of burns and diabetic ulcers &'uchs et al
4??().
"oday$ tissue en#ineerin# efforts are bein# undertaken for eery type of tissue and or#an &2ee 'i#. >).
'i#. >. "issue en#ineerin# process &'uchs et al 4??().
2.(. Tissue Enineered Heart Valves
"eebken et al &4??4) ar#ued that for substitution of diseased ales althou#h human ale allo#rafts hae
become more widely used as compared to bioprosthetic and prosthetic ales they are not aailable due to
donor scarcity. "he use of #lutaraldehyde-fixed xeno#rafts$ which are abundant$ may oercome this problem
but xeno#rafts are not iable structures.
"eebken et al &4??4) analysed the processin# of allo#eneic and xeno#eneic acellular matrix scaffolds of
pulmonary heart ales after in itro seedin# with the use of auto#olous cells. "hey found that both the
decellulari%ation process and the in itro tissue en#ineerin# approach usin# acellular matrix conduit lead to in
io reconstitution of iable heart ale tissue. 8oweer$ half of the seeded tissue-en#ineered conduits
de#enerated after = months. "hey related this foundin# to the immonolo#ic modulation of autolo#ous cells
durin# to culture period prior to implantation. ,s a result they concluded that new methods are to be
necessary to control cell differentiation durin# cell expansion prior to implantation
Ehristopher et al &(==@) worked on tissue en#ineered leaflets that are constructed by serially seedin#
autolo#ous oine fibroblast endothelial cells onto a biode#radable synthetic matrix composed of copolymer
of poly#lycolic and polylactic acid. "hey reported that the structure and function of the tissue en#ineered
constructs approaches those of natie tissue when they are exposed to physiolo#ical forces oer an extended
period of time.
2odian et al &4???) created a tissue-en#ineered trileaflet ale from porous /8, and ascular cells and
constructed it into the pulmonary position. "he ales showed no thrombus formation and minimal
re#ur#itation. Eolla#en content increased oer time showin# continued remodellin#.
,nother study was performed usin# composite scaffolds of /B,-/<8B by 8oerstrupt et al &4???). "he
composite scaffolds were #rown for (< days in a pulse duplicator in itro system under #radually increasin#
flow and pressure. 'i#. @ refers the tissue en#ineered heart ale after (< days of pulsatile flow in a
bioreactor. "he ale constructs were then implanted to same lambs and explanted at different time points.
,fter functioned up to > months histolo#ically$ mechanically and in terms of extracellular matrix formation
the auto#olous tissue en#ineered ales resembled the normal heart ales.
'i# @. "issue-en#ineered heart ale after (< days of pulsatile flow in a bioreactor &8oerstrupt et al 4???)
8oerstrup et al &4??4) inesti#ated the autolo#ous pulmonary artery conduit tissue en#ineered from human
umbilical cord cells. "hey first harested the human umbilical cord cells and expanded in the culture. "hen
they seeded the pulmonary conduits fabricated from rapidly bioabsorbable polymers with umbilical cord
cells. "hey obsered iable$ layered tissue and stracellular matrix formation with #lycosamineo#lycans and
colla#ens. "heir 291 results showed confluent$ homo#enous tissue surfaces. 9xtracellular matrix proteins
were si#nificantly lowered compared with natie tissue$ and the mechanical stren#th of the constructs was
also comparable with natie tissue. "he results are #ien in 'i#ures D and A. "hus$ they concluded that
human umbilical cord cells demonstrated excellent #rowth properties representin# a new$ readily aailable
cell source for tissue en#ineerin# without necessitatin# the sacrifice of intact ascular donor structures.
'i#. D. 'i#.A
'i#.D "wo iews &, and B) of tissue en#ineered pulmonary artery conduit after (< days conditionin# in the
pulse duplicator bioreactor &dimensions7 len#th$ <? mmF inner diameter$ (A mmF wall thickness$ ( mm).
'i#. A &,) 2cannin# electron microscopy of the pulsed conduits showed dense tissue formation
and a confluent smooth surface. &B) In contrast$ static controls were less homo#eneous. &E)
"ransmission electron microscopy reealed cell elements typical of secretionally actie
myofibroblasts such as colla#en fibrils &asterisk) and elastin &white arrow)$8oerstrup et al 4??4
Guttelman et al &4??4) deeloped a second #eneration of /V,-based scaffolds that inte#rates the adanta#es
of /V, &hi#h water content$ tissue like elasticity$ and ability to attached a ariety of molecules) with those of
/0, &de#radability$ ability to photocrosslinkin# and hydrophobicity). "hey reported that this material has
#reat potential as a tissue-en#ineerin# scaffold due to ability to control the rate of network de#radation$ mass
erosion profile and its bulk chemical properties. In their studies$ ale interstitial cells were seeded on two-
dimensional surfaces of arious compositions of /V,-3e#. "hey attributed the increased cell attachment
increased adsorption of cell adhesion proteins to hydrophobic #els.
"oshiharu et al &(==>) tested the feasibility of constructin# heart ale leaflets in lambs by seedin# a
synthetic$ poly#lycolic acid fiber matrix in io with fibroblast and endothelial cells. "hey used the
followin# methodF mixed cell populations were isolated from explanted oine arteries. 9ndothelial cells were
selectiely labelled with low-density lipoprotein marker and by usin# a fluorescent actiated cell sorterF they
are separated from the fibroblast. "hen they produced a tissue like sheet which was made up of a synthetic
biode#radable polymer scaffold constructed from poly#lycolic acid fibers that was seeded with fibroblast.
"his tissue was then seeded with endothelial cells$ which formed a monolayer coatin# around the leaflet.
'inally$ autolo#ous and allo#enic tissue en#ineered leaflets were implanted in seen animals. ,fter these
experiments they concluded that tissue en#ineerin# constructed ale leaflet from its cellular components can
function in the pulmonary ale position.
Hund et al &(==D) demonstrated the in itro creation of tissue en#ineered heart ale tissue usin#
cardioascular cells on de#radable polymer matrices. "hey created the xeno#raft leaflets from human dermal
fibroblast and boine aortic endothelial cells and the allo#raft ale leaflets from sheep myofibroblast and
sheep endothelial cells.
"hey constructed a heart ale leaflet by usin# a polymeric scaffold composed of poly#lycolic acid &/B,)
and copolymer of poly#lycolic and polylactic acid &/0,). "hey used two kinds of leaflets that are leaflets
constructed with a non-woen mesh and sandwich type leaflets. ;uter layer was constructed from a non-
woen mesh made from pure /B, fibers and an inner layer with a woen mesh made from a /B,
copolymer consistin# of =?I /B, and (?I /0, "he polymers were constructed as square sheets with a
surface area of = cm
4
.
,fter seedin#$ the xeno#raft constructs were examined by conentional histolo#y and immune histolo#y by
usin# markers for endothelial cells and myofibroblasts and smooth muscle cells. 2imilarly$ after harestin#
aortic heart ale cells from lambs the tissue was serially washed with phosphate buffered saline. Cnder a
laminar flow hood$ the tissue was minced into (J4 mm pieces and eenly distributed in (>K@? mm tissue
culture dishes$ and then #ently added to the tissue culture dishes so as not to disrupt the explants. "hey
placed the explanted in a humidified incubator at :DLE with >I E;
4
for @J(? weeks. 3urin# this time
period$ the cells mi#rated off the explants formin# mixed cell populations. ,fter the mixed cell population
had #rown to confluence$ the cells were labelled with an acetylated-low density lipoprotein &,c-3il-030).
"hese cells were then separated into 030 positie and 030 ne#atie populations usin# fluorescence
actiated cell sorter. "he 030 ne#atie mixed population was seeded onto the polymeric scaffold each day
oer a (4-day period. "his tissue-like structure was then seeded with :K(?
@
cells of the pure population of
endothelial &030 positie) cells. ,fter (< days$ conentional histolo#y and immunhistolo#y examined the
constructs by stainin# for factor VIII.
,s a result they produced <? tissue en#ineered heart ale leaflets &4? xeno#raft and 4? allo#raft leaflets).
1icroscopic examination of fibroblasts seeded on non-woen /B, mesh demonstrated that the human
fibroblasts were attached to the polymeric fibers and had be#un to spread out and diide &see 'i#ure =). ,t
the end of the twelfth day of seedin# the scaffold resembled a solid sheet of tissue. ,fter seedin# of this
tissue-like structure with boine endothelial cells$ an endothelial monolayer formed on the surface of the
fibroblasts. 'actor VIII stainin# demonstrated no apparent inasion of the structure by endothelial cells nor
formation of new capillary endothelial structures.

'i#. =. 'ormation of fibroblast-polymer brid#es. "his fi#ure demonstrates polymer fiber &,) attachment of
Biemsa stained fibroblast &B) and the formation of fibroblast cross brid#es &E) between polymer fibers.
&Hund et al (==D)
"hey further obsered after immunohistochemical analysis of the 030 positie and 030 ne#atie sheep
aortic-ale-cell populations that the 030 positie population stained with factor VIII resembled a pure
population of endothelial cells. ,fter stainin# for actin$ the 030 ne#atie population morpholo#ically
resembled either smooth muscle cells or myofibroblasts. "hey then seeded the sandwich-constructed leaflets
eery other day with (?
@
030 ne#atie cells. ,fter (4 days$ the tissue-en#ineered constructs were seeded
with :K(?
@
030 positie cells. 9ndothelial cells formed a monolayer on the surface of the allo#enic mixed
cell population of myofibroblasts and smooth muscle cells with no apparent inasion of the structure by
endothelial cells nor formation of new capillary endothelial structures &see 'i#ure (?). "his new tissue
en#ineered heart ale leaflet histolo#ical resembled natie ale tissue and was stron#er and stiffer than the
ori#inal tissue en#ineered leaflets as demonstrated by physical exams.

'i#. (?. Immunoperoxidase stainin# for endothelial factor VIII on tissue en#ineered heart ale. 1onolayer
of lamb aortic ale endothelia identified by stainin# for factor VIII &,) on the surface of a fibroblast and
smooth-muscle cell matrix &cross-section). Gote neither apparent inasion of the structure by endothelial
cells nor formation of new capillary endothelial structures. &Hund et al (==D)
"o sum up$ Hund et al demonstrated that they can successfully construct a new heart ale leaflet that has
both morpholo#ical and histolo#ical similarity to a natie heart ale. "hey further continue the functional
testin# of this new ale by either placin# it &a) into an animal or &b) under conditions of simulated heart
function &e#. bioreactor). But they ar#ued the adanta#es and disadanta#es of these two methods of
ealuation. "he adanta#e of an animal model is the maintenance of sterile and physiolo#ical conditions$
whereas in a bioreactor lon#-term follow up of the tissue-en#ineered ale appears to be more complicated.
;n the other hand the bioreactor allows one to carefully control independent ariables which are important
for alular deelopment such as the pulsatile pressure$ temperature$ oxy#en saturation$ #rowth factors and
iscosity.
IV. +9'9+9GE92
Bader ,.$ 2chillin# ".$ "eebken ;.9. et al.$ Eur j Cardiothorac Surg (< &(==A)$ 4D=-4A<
Barnard E.G.$ ,m M Eardiol 44 &(=A@)F >A<->=@
Breuer E.N.$ 2hinoka ".$ 1ayer M.9.$ 0an#er +.$ Vacanti M./.$ Eardioasc /athol
ol.>$Go.>F (==@F 4A@-:?4
Ehick 6.0.$ 0ike ,.,.$ 0auris V.$ 2cience (AD &(=D>)F A<D-A<=
3ai 6$ Belt M.$ 2alt%man 6.1.$ BioO"ech (==<F (4FD=D-A?(
'reed 0.9.$ Vun5ak-Goakoic B.$ Biron +.M. et al.$ BioO"ech Vol.(4$ (==<.
'uchs M.+.$ Gasseri B.,.$ Vacanti M./.$ 4??($ Vol D4$ Issue 4F >DD->=(.
8oerstrupt 2./.$ Nadner ,.$ Breyman E.$ 1aurus E.'.$ Buenter E.I.$ 2odian +.$ Vis5a#er M.'.$
Hund B.$ "urina 1.I.$ 4??4$ "he 2ociety of "horacic 2ur#ery$ D<F<@->4.
8oerstrupt 2./.$ 2odian +.$ 3aebrit% et al.$ 4???$ Eirculation (?4 &4???)$ 4=4-4==.
Guttelman E.+.$ 8enry 2.1.$ ,nseth N.2.$ Biomaterials 4??4$ 4:F:@(D-:@4@.
;!Brien 1.'.$ Boldstein 2.$ 6alsh 2.$ Black N.2.$ 9lkins +.$ Elarke 3.$
2emin "horac Eardioasc 2ur#$ (( &(===)$ (=<-4??.
/achence M.1 and Nohn M.$ /rinciples of "issue 9n#ineerin#$ Ehp.(=$ (==D +.B.
0andess Eompany. &editors7 0an%a +$ 0an#er +$ Ehick 6)
2alt%man 1.6.$ /rinciples of "issue 9n#ineerin#$ Ehp.(@$ (==D +.B. 0andess Eompany.
&editors7 0an%a +$ 0an#er +$ Ehick 6)
2hinoka "$ Breuer E.N.$ "anel +.9.$ Hund B.$ 1iura ".$ 1a /.P.$ 0an#er +.$ Vacanti M./.$
1ayer M.9.$ (==> "he 2ociety of "horacic 2ur#ions
2odian +.$ 8oerstrup 2./.$ 2perlin# M.2. et al.$ Eirculation (?4 &4???)$III44-III4=.
"eekbken ;.9.$ 1ertschin# 8. and 8aerich ,.$ "ransplantation /roceedin#s$ :<$ 4:::: &4??4)
"homson +.E.$ Qas%emski 1.M.$ 1ikos ,.B.$ /rinciples of "issue 9n#ineerin#$ Ehp.(=$ (==D
+.B. 0andess Eompany. &editors7 0an%a +$ 0an#er +$ Ehick 6)
Hund B.$ Breuer E.N.$ 2hinoka ".$ 1a /.P.$ 0an#er +.$ 1ayer M.9.$ Vacanti M./.$
9 M Eardio-thoracic 2ur#ery$ (==DF ((F <=:-<=D
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