NANOFIBER BASED SCAFFOLD FABRICATION, CHARACTERIZATION AND OPTIMIZATION FOR TISSUE ENGINEERING AORTIC HEART VALVE EHSAN FALLAHI AREZOUDAR A thesis submitted in fulfilment of the requirements for the award of the degree of Doctor of Philosophy (Mechanical Engineering) Faculty of Mechanical Engineering Universiti Teknologi Malaysia FEBRUARY 2017
67
Embed
NANOFIBER BASED SCAFFOLD FABRICATION, …3.6.5.1 Blood Clotting Time (PT & TT Assay) 75 3.6.5.2 Fibrin Formation 76 3.6.5.3 Hemolysis Test 76 3.6.6 Mechanical Properties of Electrospun
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
NANOFIBER BASED SCAFFOLD FABRICATION, CHARACTERIZATION
AND OPTIMIZATION FOR TISSUE ENGINEERING AORTIC HEART VALVE
EHSAN FALLAHI AREZOUDAR
A thesis submitted in fulfilment o f the
requirements for the award o f the degree o f
Doctor o f Philosophy (Mechanical Engineering)
Faculty o f Mechanical Engineering
Universiti Teknologi Malaysia
FEBRUARY 2017
lll
To my beloved family
lv
ACKNOWLEDGEMENT
First and above all, I praise God, the almighty for providing me this
opportunity and granting me the capability to proceed with this research successfully.
Further, there are no proper words to convey my deep gratitude and respect for my
thesis and research advisor, Professor Dr. Noordin Mohd Yusof. He has inspired me
to become an independent researcher and helped me realize the power of critical
reasoning. He also demonstrated what a brilliant and hard-working scientist can
accomplish.
My sincere thanks must also go to co-advisory, Professor Dr. Ani Idris for the
trust, the insightful discussion, offering valuable advice, for her support during the
whole period of the study, and especially for her patience and guidance during the
writing process. She generously gave her time to offer me valuable comments toward
improving my work.
Besides, I would like to thank the authority of Universiti Teknologi Malaysia
(UTM) for providing me with a good environment and facilities. I also greatly
appreciate the excellent assistance and spiritual supports of my family and my friends
during my PhD study.
v
ABSTRACT
The four valves in a mammalian heart provide a unidirectional, unobstructed blood flow pathway as a result of synchronic movement of valves’ leaflets during cardiac cycle. When one of the valves malfunctions, the medical choice is to replace the original valve with an artificial one. However, the inability to grow or to remodel an artificial valve leads to the innovation of tissue engineering heart valve (TEHV). The previously tissue engineered heart valve tends to be rigid, have low degradation rate and adverse structure which leads to TEHV failure. This study presents the design and fabrication of an aortic heart valve (AOHV) based on tissue engineering (TE) principle via electrospinning method. In TE, a three-dimensional (3D) scaffold with proper design, structure, and mechanical properties that resembles the original tissue is required as an initial template for tissue regeneration. For this purpose, materials’ ratio tuning and process optimization as well as the 3D scaffold design were considered. Initially, five different ratios of poly-L-lactic acid (PLLA)/thermoplastic polyurethane (TPU) blends containing 1% (w/v) maghemite (y-Fe2O3) nanoparticles were electrospun and characterized in terms of morphology, degradation rate, biological compatibility and mechanical properties. The existence of three components in the mats was confirmed by Fourier transform infrared and energy-dispersive X-ray spectroscopy. Scanning electron microscopy images illustrated well fabricated nanofibers with smaller diameter distribution for PLLA. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay using human skin fibroblast cell indicates desired proliferation on the samples. Blood biocompatibility results in terms of clotting time, fibrin formation, and hemolysis were almost in the normal range. Samples’ degradation rate was investigated over 24 weeks where the PLLA shows 47.15% loss in mass versus 6.7% loss for TPU. High tensile strength and an extremely low elongation-at-break were determined from the stress-strain curve for PLLA, while TPU exhibits high elasticity. Overall, 50:50% of (1% y-Fe2O3) loaded PLLA/TPU mats are the most appropriate. Next, a two-level Taguchi (L8) experimental design followed by the response surface methodology (RSM) were used to optimize the fabrication process where the elastic modulus is the response while the factors investigated were A-flow rate (2-3 ml/h), B-voltage (20-30 kV), C- maghemite% (1-3% w/v), D-solution concentration (10-15 wt.%) and E-collector rotating speed (1000-2000 rpm). From the signal-to-noise ratio values, the influences of the factors were ranked as: D>B>C>E>A. The empirical quadratic model obtained consists of the voltage-B and second order effect of flow rate-(A)2, voltage-(B)2, maghemite %-(C)2 and concentration-(D)2. The optimum elastic modulus of the scaffold was found to be 35.24±0.64 MPa. Finally, an AOHV template was designed and installed as the electrospinning collector to fabricate the 3D scaffold based on the optimum ratio and settings. Later, the human aortic smooth muscles cell migration and proliferation, as well as the elastic modulus loss percent of the optimum 3D scaffold after cell seeding were checked during 34 days of incubation. Overall, the structural, biological and mechanical specifications of the fabricated TEHV have successfully proved that it can be a potential alternative in AOHV replacement surgery.
Empat injap yang terdapat di dalam hati mamalia menyediakan laluan aliran darah yang searah, tidak terhalang disebabkan pergerakan daun injab yang diselarikan semasa kitaran jantung. Apabila salah satu daripada injap rosak, pilihan perubatan adalah menggantikan injap asal dengan injap tiruan. Walaubagaimanapun, injap tiruan tidak mempunyai kemampuan untuk tumbuh atau dimodel semula. Ini telah membawa kepada inovasi injap jantung kejuruteraan tisu (TEHV). Injap jantung kejuruteraan tisu sebelum ini adalah tegar, mempunyai kadar penurunan yang rendah dan struktur yang tidak sesuai yang membawa kepada kegagalan TEHV. Kajian ini membentangkan reka bentuk dan fabrikasi injap jantung aortik menggunakan prinsip kejuruteraan tisu (TE) melalui kaedah elektropintal. Dalam TE, perancah tiga dimensi (3D) dengan reka bentuk yang sesuai, struktur dan sifat-sifat mekanik yang boleh menyerupai tisu asal akan digunakan sebagai pencontoh permulaan untuk pertumbuhan semula tisu. Untuk tujuan ini, penalaan nisbah bahan-bahan utama yang digunakan dan pengoptimuman proses serta reka bentuk perancah 3D dipertimbangkan. Buat permulaan, lima nisbah berbeza poli-L-laktik asid (PLLA)/poliuretana termoplastik (TPU) dicampurkan dengan 1% (w/v) maghemite (y-Fe2O3) nanopartikel. Campuran ini telah melalui proses elektropintal dan pencirian dibuat dari segi morfologi, kadar penurunan, keserasian biologi dan sifat-sifat mekanik. Kewujudan tiga komponen dalam lapisan serat nano telah disahkan oleh jelmaan inframerah Fourier dan serakan-tenaga X-ray spektroskopi. Imej imbasan mikroskopi elektron menunjukkan bahawa serat nano yang baik terhasil dengan garis pusat yang lebih kecil untuk PLLA. Kajian MTT menggunakan sel fibroblas kulit manusia dan ia menunjukkan percambahan yang baik ke atas sampel. Keputusan bio-keserasian darah dari segi masa pembekuan, pembentukan fibrin, dan hemolisis hampir dalam julat normal. Kadar penurunan sampel telah diselidiki selama 24 minggu yang mana PLLA menunjukkan penurunan jisim sebanyak 47.15% berbanding dengan penurunan 6.7% bagi TPU. Kekuatan tegangan yang tinggi dan kadar pemanjangan sebelum putus yang amat rendah ditentukan dari lengkung tegasan-terikan untuk PLLA, manakala TPU mempamerkan keanjalan yang tinggi. Secara keseluruhan, lapisan serat nano PLLA/TPU yang mengandungi 50:50% daripada 1% (y-Fe2O3) adalah yang paling sesuai. Seterusnya, reka bentuk eksperimen dua aras Taguchi (L8) diikuti dengan kaedah gerak balas permukaan (RSM) telah digunakan untuk mengoptimumkan proses di mana modulus elastik merupakan sambutan manakala faktor yang dikaji ialah A- kadar alir (2-3 ml/h), B- voltan (20-30 kV), C-maghemite % (1-3% w/v), D-kepekatan larutan (10-15wt.%), dan E- kelajuan puteran pengumpul (1000-2000 rpm). Dari nilai nisbah isyarat-kepada-hingar (S/N), pengaruh faktor adalah: D>B>C>E>A. Model kuadratik empirikal yang diperolehi terdiri dari voltan-B dan kesan peringkat kedua kadar alir-(A)2, voltan-(B)2, maghemite %-(C)2 dan kepekatan-(D)2. Modulus elastik optimum perancah yang diperolehi adalah 35.24±0.64 MPa. Akhir sekali, AOHV telah direka dan dipasang sebagai pemungut kepada elektropintal untuk menghasilkan perancah 3D berdasarkan kepada nisbah optimum dan tetapan. Kemudian, penghijrahan dan perkembangan aortik sel-sel otot licin manusia serta peratusan kehilangan keanjalan modulus daripada perancah 3D optimum selepas pembenihan sel diperiksa semasa 34 hari pengeraman. Secara keseluruhan, spesifikasi struktur, biologi dan mekanikal bagi TEHV yang telah difabrikasi berjaya membuktikan yang ia boleh menjadi alternatif yang berpotensi untuk pembedahan penggantian AOHV.
vii
TABLE OF CONTENTS
CHAPTER TITLE PAGE
DECLARATION ii
DEDICATION iii
ACKNOWLEDGEMENT iv
ABSTRACT v
ABSTRAK vi
TABLE OF CONTENTS vii
LIST OF TABLES xii
LIST OF FIGURES xiv
LIST OF ABBREVIATIONS xix
LIST OF SYMBOLS xxii
LIST OF APPENDICES xxv
1 INTRODUCTION 1
1.1 Overview of the Research 1
1.2 Research Problem Statement 8
1.3 Research Questions 10
1.4 Research Hypothesis 11
1.5 Research Aim and Objectives 11
1.6 Research Scopes 12
1.7 Significance of Research 14
1.8 Organization of Thesis 14
2 LITERATURE REVIEW
2.1 Introduction
15
15
2.2 Overview of Heart Valves 15
2.3 Aortic Heart Valve 18
2.3.1 Microstructure and Function of Normal Aortic
Valve 18
2.3.2 Mechanical Properties of the Aortic Heart Valve 22
2.3.2.1 Uniaxial and Biaxial Mechanical
Properties 23
2.3.2.2 Flexural Mechanical Properties 28
2.3.3 Aortic Valves Pathology 29
2.4 Tissue Engineering Heart Valve (TEHV) 31
2.4.1 Three-dimensional Heart Valves Scaffold 32
2.4.1.1 Polymeric and Biological Materials 32
2.4.1.2 Scaffolds Fabrication Techniques 42
2.4.1.3 Synthetic Scaffolds Mechanical
Properties 47
2.4.2 Cells Sources and Cultivation Methods 48
2.4.2.1 Adipose-derived Cells 50
2.4.2.2 Valve Interstitial Cells 50
2.4.2.3 Bone Marrow Stem Cells 51
2.4.3 Development Condition 52
2.5 Summary 53
3 RESEARCH METHODOLOGY 55
3.1 Introduction 55
3.2 Research Framework 55
3.3 Materials Requirement 59
3.4 Solution Preparation 61
3.4.1 Synthesizing Maghemite (y-Fe2O3) 61
3.4.2 Poly-L-lactic Acid (PLLA) and
Thermoplastic Polyurethane (TPU) 61
3.5 Electrospinning Setup to Fabricate PLLA/TPU-(y-Fe2O3)
Nanofiber Mats 62
3.5.1 Chemically Characterization of Electrospun Mats 64
viii
3.6 Materials Ratio Tuning Process 64
3.6.1 Morphology and Porosity 65
3.6.2 Hydrophilicity and Surface Roughness 66
3.6.3 Degradation Rate of Electrospun Mats 67
3.6.3.1 Changes in Morphology 67
3.6.3.2 Mass Change of Electrospun Mats 68
3.6.3.3 Porosity (%) Change 68
3.6.4 Cell Biological Compatibility Tests 68
3.6.4.1 Fibroblast Cell Thawing, Plating and
Sub-culturing 69
3.6.4.2 Cell Cytotoxicity Assay and Cell
Viability (MTT Assay) 70
3.6.4.3 Cells Attachment 74
3.6.5 Blood Hemocompatibility 74
3.6.5.1 Blood Clotting Time (PT & TT Assay) 75
3.6.5.2 Fibrin Formation 76
3.6.5.3 Hemolysis Test 76
3.6.6 Mechanical Properties of Electrospun Mats 77
3.7 Fabrication Process (Electrospinning) Optimization 79
3.7.1 Two-level Taguchi Experimental Design 79
3.7.1.1 Test for Significance of the Regression
Model 83
3.7.1.2 Test for Significance on Individual
Model Terms 83
3.7.1.3 Test for Lack-of-fit 84
3.7.2 Steepest Ascent Method 85
3.7.3 Response Surface Methodology (RSM) 87
3.8 Design the 3D Semilunar Heart Valve Template 88
3.9 Characterizations of 3D Heart Valve Scaffold 91
Pathway o f blood flow through the heart and lungs. Oxygenated blood flow (red colour) transfer from the lungs to the left ventricles and deoxygenated blood (blue colour) returns from the body to the right ventricle
Structures o f atrioventricular valve (mitral and tricuspid) include the leaflets, annulus, chordae tendineae, and papillary muscles
Schematic semilunar valves (a) top view o f lateral section o f outflow vessel during diastole to show the close valve,(b) by cutting longitudinally the vessel between two leaflets
Schematic diagram of aortic valve leaflet layers and components
Biaxial mechanical behaviour of aortic heart valve leaflets radially and circumferentially
Biological, mechanical and physiochemical properties of commonly studied biodegradable natural and synthetic polymer
Chemical structure formula of (a) poly-L-lactic acid (b) thermoplastic polyurethane
Research framework in (a) summary form (b) detailed form
Electrospinning setup to fabricate PLLA/TPU-(y-Fe2O3) nanofibers
PAGE
2
3
4
7
16
17
18
22
27
37
39
56
63
3.3
3.4
3.5
3.6
3.7
3.8
3.9
3.10
3.11
3.12
3.13
4.1
4.2
4.3
4.4
4.5
4.6
4.7
4.8
4.9
4.10
Image of hemocytometer gridlines for under microscope cells counting
Layout of samples loading in 24-well plate
MTT assay procedure
Stress versus strain uniaxial tensile test
Linear graph for Taguchi L8 design
First order response surface and path of steepest ascent
Two-dimensional central composite design experiments with level (a)
Human aortic heart valve geometrical parameters
Design of aluminium based template to be used as collector
3D printed based design of aortic heart valve template
Schematic diagram of macro-indentation test
Characterization of (y-Fe2O3) nanoparticles (a) XRD pattern (b) TEM images (c) reference of maghemite XRD pattern
FTIR spectra of (a) TPU, PLLA, PLLA/TPU and PLLA/TPU-(y-Fe2O3) (b) references of PLLA and TPU polymers
EDX graphs of elements presented in PLLA/TPU and PLLA/TPU-(y-Fe2O3)
DSC heating curve of PLLA/TPU and PLLA/TPU-(y- Fe2O3)
FE-SEM images of nanostructure and diameter distribution of (a) 100:0% (b) 75:25% (c) 50:50% (d) 25:75% and (e) 0:100% PLLA/TPU-(y-Fe2 O3) scaffold
TEM image of 50:50% PLLA/TPU-(y-Fe2 O3)
Porosity (%) of different ratios of PLLA/TPU-(y-Fe2O3) electrospun mats
Water contact angle measurement of (a) 100:0% (b) 75:25% (c) 50:50% (d) 25:75% and (e) 0:100% PLLA/TPU-(y-Fe2O3) nanofibers
AFM results of surface roughness, 3D micrograph and region profile for (a) 100:0% (b) 75:25% (c) 50:50% (d) 25:75% and (e) 0:100% of PLLA/TPU-(y-Fe2 O3) scaffold
Correlation between porosity, hydrophilicity and surface roughness
71
72
73
78
80
86
87
88
90
91
95
98
100
101
102
104
105
106
107
109
110
xv
xvi
4.11
4.12
4.13
4.14
4.15
4.16
4.17
4.18
4.19
4.20
4.21
4.22
4.23
4.24
4.25
4.26
FE-SEM images of degradation rate of different ratios of PLLA/TPU-(y-Fe2O3) scaffolds in weeks 1, 4, 6, 12 and 24 of immersion 113
Change of mass (mg) as a function of degradation time 116
EDX graph of 50:50% PLLA/TPU-(y-Fe2O3) after 4 weeks of immersion in SBF 117
Change in porosity (%) as a function of degradation time 118
The well plate analysis of (a) cytotoxicity assay (b) MTT assay of different ratios of PLLA/TPU-(y-Fe2O3) scaffold during 1, 3, 5 and 7 days of incubation 119
Cytotoxicity result during 72 h of incubation 120
Results of relative cell viability versus the incubation time (days). Each value is the mean±SD of three independent experiments. (*,p<0.05) Indicates significant differences compared to the control analyzed by one-way ANOVA 121
Results of relative cell viability for (50:50%) neat PLLA/TPU and PLLA/TPU-(y-Fe2O3) electrospun mats.(*) Significant difference compared to the control analyzedby unpaired t-test (p<0.05). (**) Indicates Significantdifferent compare to the PLLA/TPU-(y-Fe2O3) 122
FE-SEM images of HSF-1184 fibroblast cells attachmentresults on PLLA/TPU-(y-Fe2O3) electrospun mats 124
Results of (a) thrombin time (b) pro-thrombin clotting time for different ratios of PLLA/TPU-(y-Fe2O3) and neat PLLA/TPU scaffolds. (*) Significant difference compared to the control analyzed by unpaired t-test (p<0.05). (**)Indicates the significant difference between neatPLLA/TPU and PLLA/TPU containing maghemite(p<0.05) 127
Results of the first fibrin detection point by using Clot Sp. instrument in terms of (a) time (s) (b) concentration (g/L) 128
Hemo-lytic test records for different ratios of PLLA/TPU-(y-Fe2O3) electrospun mats. (*) Represents significantdifference compared to the negative control analyzed byunpaired t-test (p<0.05). (**) Indicates the significantdifference between neat PLLA/TPU and PLLA/TPUcontaining maghemite (p<0.05) 129
Mechanical stress vs. strain curve for uniaxial tensile testof different ratios of PLLA/TPU-(y-Fe2O3) electrospunmats 131
Main effect plots for mean S/N ratio of elastic modulus 134
Interaction plots data means for elastic modulus 135
Contribution percent of each parameter on elastic modulus 139
4.27
4.28
4.29
4.30
4.31
4.32
4.33
4.34
4.35
4.36
4.37
4.38
4.39
4.40
4.41
4.42
4.43
4.44
xvii
Plot of (a) normal probability (b) residual vs. predictedvalue 142
Plot of (a) 3D surface response (b) counter plot of elastic modulus 143
Pathway of steepest ascent method 144
Trend of steepest ascent steps responses of elastic modulus 146
Plot of (a) normal probability (b) residual vs. predictedvalue for CCD 150
Plot of (a) 3D surface response (b) counter plot ofquadratic model for elastic modulus 151
Plot of trend between the predicted and actual elasticmodulus 153
Exterior and interior images of 3D scaffold (aluminiumbased design) 154
Images of fabrication procedure of 3D scaffold of aorticheart valve 155
Images of (a) FE-SEM (b) diameter distribution of 156optimum 3D scaffold leaflet
Water contact angle for optimum scaffold 157
Procedure of porosity measurement using liquiddisplacement method 158
FE-SEM and CLSM images of valve’s leaflet and root in 15, 20 and 34 days of incubation. The different colours represented the live cells (Green), dead cells (Red) and scaffold (Dark) area 159
Results of 3D scaffold relative cell viability versus theincubation time (days). Each value is the mean ± SD of allthe experiments 160
Blood clotting time in terms of PT and TT assay 161
Results of the first fibrin detection for optimum scaffold in terms of concentration (g/L) and time (sec). (*) Significant difference compared to the control analyzed by unpaired t- test (p<0.05) 162
Hemo-lytic test records for PLLA/TPU containing 3.80% and 1% of (y-Fe2O3) scaffold. (*) Represents significant difference compared to the negative control analyzed by unpaired t-test (p<0.05) 163
Load vs. extension curve for optimum scaffold after 15, 20and 34 days of cell seeding 165
xviii
4.45 Elastic modulus loss as a function of incubation time (days). (*) Represents significant difference compared to the day zero (for dry scaffold) and day 15 (for wet scaffold) analyzed by unpaired t-test (p<0.05).
xix
2D - Two-dimensional
3D - Three-dimensional
Adj-R - Adjusted R-Square
ADSCs - Adipose derived stem cells
AFM - Atomic force microscopy
ANOVA - Analysis of variance
AOHV - Aortic heart valve
AV - Atrioventricular valve
BMSCs - Bone marrow stem cells
C - Carbon
CAD - Computer aided design
CCD - Central composite design
CLSM - Confocal laser scanning microscopy
CT - Computed tomography
DCM - Dichloromethane
DMF - Dimethylformamide
DMEM - Dulbecco’s modified Eagle’s medium
DMSO - Dimethyl sulfoxide
DOE - Design of experiments
DSC - Differential scanning calorimetry
ECM - Extracellular matrix
EDX - Energy dispersive X-ray
EGFP - Enhanced green fluorescent protein
LIST OF ABBREVIATIONS
xx
FBS - Fetal bovine serum
FDA - Food and drug administration
Fe - Iron
FE-SEM - Field-emission scanning electron microscopy
A r m e n t a n o , I . , B i t i n i s , N . , F o r t u n a t i , E . , M a t t i o l i , S . , R e s c i g n a n o , N . , V e r d e j o , R . , e t
a l . ( 2 0 1 3 ) . M u l t i f u n c t i o n a l n a n o s t r u c t u r e d P L A m a t e r i a l s f o r p a c k a g i n g a n d
t i s s u e e n g i n e e r i n g . Progress in Polymer Science, 3 8 ( 1 0 ) , 1 7 2 0 - 1 7 4 7 .
A u g u s t y n , C . , A l l s t o n , T . , H a i l s t o n e , R . , a n d R e e d , K . ( 2 0 1 4 ) . O n e - V e s s e l s y n t h e s i s
o f i r o n o x i d e n a n o p a r t i c l e s p r e p a r e d i n n o n - p o l a r s o l v e n t . RSC Advances,
4 ( 1 0 ) , 5 2 2 8 - 5 2 3 5 .
B a a i j e n s , F . , B o u t e n , C . , a n d D r i e s s e n , N . ( 2 0 1 0 ) . M o d e l i n g c o l l a g e n r e m o d e l i n g .
Journal o f Biomechanics, 4 3 ( 1 ) , 1 6 6 - 1 7 5 .
B a j i , A . , M a i , Y . - W . , W o n g , S . - C . , A b t a h i , M . , a n d C h e n , P . ( 2 0 1 0 ) . E l e c t r o s p i n n i n g
o f p o l y m e r n a n o f i b e r s : e f f e c t s o n o r i e n t e d m o r p h o l o g y , s t r u c t u r e s a n d t e n s i l e
p r o p e r t i e s . Composites Science and Technology, 7 0 ( 5 ) , 7 0 3 - 7 1 8 .
B a l g u i d , A . , R u b b e n s , M . P . , M o l , A . , B a n k , R . A . , B o g e r s , A . J . , V a n K a t s , J . P . , e t
a l . ( 2 0 0 7 ) . T h e r o l e o f c o l l a g e n c r o s s - l i n k s i n b i o m e c h a n i c a l b e h a v i o r o f
h u m a n a o r t i c h e a r t v a l v e l e a f l e t s - r e l e v a n c e f o r t i s s u e e n g i n e e r i n g . Tissue
Engineering, 13( 7 ) , 1 5 0 1 - 1 5 1 1 .
B a n e r j e e , R . , a n d C h e n , H . ( 1 9 9 5 ) . F u n c t i o n a l p r o p e r t i e s o f e d i b l e f i l m s u s i n g w h e y
p r o t e i n c o n c e n t r a t e . Journal o f Dairy Science, 7 8 ( 8 ) , 1 6 7 3 - 1 6 8 3 .
B a s s o , C . , M u r a r u , D . , B a d a n o , L . P . , a n d T h i e n e , G . ( 2 0 1 3 ) . A n a t o m y a n d
p a t h o l o g y o f r i g h t - s i d e d a t r i o v e n t r i c u l a r a n d s e m i l u n a r v a l v e s . I n Cardiac
Valvular Medicine ( p p . 2 1 1 - 2 2 1 ) L o n d o n : S p r i n g e r .
B e a c h , J . M . , M i h a l j e v i c , T . , S v e n s s o n , L . G . , R a j e s w a r a n , J . , M a r w i c k , T . , G r i f f i n ,
B . , e t a l . ( 2 0 1 3 ) . C o r o n a r y a r t e r y d i s e a s e a n d o u t c o m e s o f a o r t i c v a l v e
r e p l a c e m e n t f o r s e v e r e a o r t i c s t e n o s i s . Journal o f the American College o f
Cardiology, 6 1 ( 8 ) , 8 3 7 - 8 4 8 .
B e e , A . , M a s s a r t , R . , a n d N e v e u , S . ( 1 9 9 5 ) . S y n t h e s i s o f v e r y f i n e m a g h e m i t e
p a r t i c l e s . Journal o f Magnetism and Magnetic Materials, 1 4 9 ( 1 ) , 6 - 9 .
175
B e r n e , R . , a n d L e v y , M . ( 1 9 9 8 ) . S p e c i a l c i r c u l a t i o n s . Physiology. ( 4 th e d . ) St. Louis:
Mosby, 4 7 8 - 5 0 1 .
B i a n c o , P . , a n d R o b e y , P . G . ( 2 0 0 1 ) . S t e m c e l l s i n t i s s u e e n g i n e e r i n g . Nature,
4 1 4 ( 6 8 5 9 ) , 1 1 8 - 1 2 1 .
B i l l i a r , K . L . , a n d S a c k s , M . S . ( 2 0 0 0 ) . B i a x i a l m e c h a n i c a l p r o p e r t i e s o f t h e n a t i v e
a n d g l u t a r a l d e h y d e - t r e a t e d a o r t i c v a l v e c u s p : p a r t I I — a s t r u c t u r a l c o n s t i t u t i v e
m o d e l . Journal o f Biomechanical Engineering, 1 2 2 ( 4 ) , 3 2 7 - 3 3 5 .
B i s s e l l , M . M . , H e s s , A . T . , B i a s i o l l i , L . , G l a z e , S . J . , L o u d o n , M . , P i t c h e r , A . , e t a l .
( 2 0 1 3 ) . A o r t i c d i l a t i o n i n b i c u s p i d a o r t i c v a l v e d i s e a s e f l o w p a t t e r n i s a m a j o r
c o n t r i b u t o r a n d d i f f e r s w i t h v a l v e f u s i o n t y p e . Circulation: Cardiovascular
Imaging, 6( 4 ) , 4 9 9 - 5 0 7 .
C a r a b e l l o , B . A . ( 2 0 0 7 ) . A o r t i c v a l v e d i s e a s e . I n Cardiovascular Medicine, p p . 3 8 1
3 9 2 , L o n d o n : S p r i n g e r .
C h a n , K . C . , Y i n , M . C . , a n d C h a o , W . J . ( 2 0 0 7 ) . E f f e c t o f d i a l l y l t r i s u l f i d e - r i c h
g a r l i c o i l o n b l o o d c o a g u l a t i o n a n d p l a s m a a c t i v i t y o f a n t i c o a g u l a t i o n f a c t o r s
i n r a t s . Food and Chemical Toxicology, 4 5 ( 3 ) , 5 0 2 - 5 0 7 .
C h a v a r r i a , F . , a n d P a u l , D . ( 2 0 0 6 ) . M o r p h o l o g y a n d p r o p e r t i e s o f t h e r m o p l a s t i c
p o l y u r e t h a n e n a n o c o m p o s i t e s : E f f e c t o f o r g a n o c l a y s t r u c t u r e . Polymer,
4 7 ( 2 2 ) , 7 7 6 0 - 7 7 7 3 .
C h e n , R . , H u a n g , C . , K e , Q . , H e , C . , W a n g , H . , a n d M o , X . ( 2 0 1 0 ) . P r e p a r a t i o n a n d
c h a r a c t e r i z a t i o n o f c o a x i a l e l e c t r o s p u n t h e r m o p l a s t i c p o l y u r e t h a n e / c o l l a g e n
c o m p o u n d n a n o f i b e r s f o r t i s s u e e n g i n e e r i n g a p p l i c a t i o n s . Colloids and
C h e v a l l a y , B . , a n d H e r b a g e , D . ( 2 0 0 0 ) . C o l l a g e n - b a s e d b i o m a t e r i a l s a s 3 D s c a f f o l d
f o r c e l l c u l t u r e s : a p p l i c a t i o n s f o r t i s s u e e n g i n e e r i n g a n d g e n e t h e r a p y .
Medical and Biological Engineering and Computing, 3 8 ( 2 ) , 2 1 1 - 2 1 8 .
C h i o n o , V . , M o z e t i c , P . , B o f f i t o , M . , S a r t o r i , S . , G i o f f r e d i , E . , S i l v e s t r i , A . , e t a l .
( 2 0 1 4 ) . P o l y u r e t h a n e - b a s e d s c a f f o l d s f o r m y o c a r d i a l t i s s u e e n g i n e e r i n g .
Interface Focus, 4 ( 1 ) , 4 5 - 5 3 .
C h i r i t a , M . , G r o z e s c u , I . , T a u b e r t , L . , R a d u l e s c u , H . , P r i n c z , E . , S t e f a n o v i t s - B a n y a i ,
E . , e t a l . ( 2 0 0 9 ) . F e 2 O 3 - n a n o p a r t i c l e s , p h y s i c a l p r o p e r t i e s a n d t h e i r
p h o t o c h e m i c a l a n d p h o t o e l e c t r o c h e m i c a l a p p l i c a t i o n s . Chemical Bulletin, 54,
1 - 8 .
C h o i , S . H . , a n d P a r k , T . G . ( 2 0 0 2 ) . S y n t h e s i s a n d c h a r a c t e r i z a t i o n o f e l a s t i c
P L G A / P C L / P L G A t r i - b l o c k c o p o l y m e r s . Journal o f Biomaterials Science,
D a n i l e v i c i u s , P . , G e o r g i a d i , L . , P a t e m a n , C . J . , C l a e y s s e n s , F . , C h a t z i n i k o l a i d o u , M . ,
a n d F a r s a r i , M . ( 2 0 1 5 ) . T h e e f f e c t o f p o r o s i t y o n c e l l i n g r o w t h i n t o a c c u r a t e l y
d e f i n e d , l a s e r - m a d e , p o l y l a c t i d e - b a s e d 3 D s c a f f o l d s . Applied Surface Science,
336, 2 - 1 0 .
D a s i , L . P . , S i m o n , H . A . , S u c o s k y , P . , a n d Y o g a n a t h a n , A . P . ( 2 0 0 9 ) . F l u i d
m e c h a n i c s o f a r t i f i c i a l h e a r t v a l v e s . Clinical and Experimental Pharmacology
and Physiology, 3 6 ( 2 ) , 2 2 5 - 2 3 7 .
D a v i d , H . , B o u g h n e r , D . R . , V e s e l y , I . , a n d G e r o s a , G . ( 1 9 9 4 ) . T h e p u l m o n a r y v a l v e :
I s i t m e c h a n i c a l l y s u i t a b l e f o r u s e a s a n a o r t i c v a l v e r e p l a c e m e n t ? ASAIO
Journal, 4 0 ( 2 ) , 2 0 6 - 2 1 2 .
178
D e b , A . , W a n g , S . H . , S k e l d i n g , K . , M i l l e r , D . , S i m p e r , D . , a n d C a p l i c e , N . ( 2 0 0 5 ) .
B o n e m a r r o w - d e r i v e d m y o f i b r o b l a s t s a r e p r e s e n t i n a d u l t h u m a n h e a r t v a l v e s .
The Journal o f Heart Valve Disease, 1 4 ( 5 ) , 6 7 4 - 6 7 8 .
D e H e e r , L . M . , H a b e t s , J . , K l u i n , J . , S t e l l a , P . R . , W i l l e m , P . T . M . , v a n H e r w e r d e n ,
L . A . , e t a l . ( 2 0 1 3 ) . A s s e s s m e n t o f a t r a n s c a t h e t e r h e a r t v a l v e p r o s t h e s i s w i t h
m u l t i d e t e c t o r c o m p u t e d t o m o g r a p h y : i n v i t r o a n d i n v i v o i m a g i n g
c h a r a c t e r i s t i c s . The International Journal o f Cardiovascular Imaging, 2 9 ( 3 ) ,
6 5 9 - 6 6 8 .
D e n g , Y . , L i u , X . , X u , A . , W a n g , L . , L u o , Z . , Z h e n g , Y . , e t a l . ( 2 0 1 5 ) . e f f e c t o f
s u r f a c e r o u g h n e s s o n o s t e o g e n e s i s i n v i t r o a n d o s s e o i n t e g r a t i o n i n v i v o o f
c a r b o n f i b e r - r e i n f o r c e d p o l y e t h e r e t h e r k e t o n e - n a n o h y d r o x y a p a t i t e c o m p o s i t e .
International Journal o f Nanomedicine, 10, 1 4 2 5 - 1 4 4 7 .
D h a n d a y u t h a p a n i , B . , Y o s h i d a , Y . , M a e k a w a , T . , a n d K u m a r , D . S . ( 2 0 1 1 ) .
P o l y m e r i c s c a f f o l d s i n t i s s u e e n g i n e e r i n g a p p l i c a t i o n : A - r e v i e w .
International Journal o f Polymer Science, 2011, 1 - 1 9 .
D r i e s s e n , N . J . , M o l , A . , B o u t e n , C . V . , a n d B a a i j e n s , F . P . ( 2 0 0 7 ) . M o d e l i n g t h e
m e c h a n i c s o f t i s s u e - e n g i n e e r e d h u m a n h e a r t v a l v e l e a f l e t s . Journal o f
Biomechanics, 4 0 ( 2 ) , 3 2 5 - 3 3 4 .
D u a n , B . , K a p e t a n o v i c , E . , H o c k a d a y , L . , a n d B u t c h e r , J . ( 2 0 1 4 ) . T h r e e - d i m e n s i o n a l
p r i n t e d t r i l e a f l e t v a l v e c o n d u i t s u s i n g b i o l o g i c a l h y d r o g e l s a n d h u m a n v a l v e
i n t e r s t i t i a l c e l l s . Acta Biomaterialia, 1 0 ( 5 ) , 1 8 3 6 - 1 8 4 6 .
D u n k l e , T . , D e s c h a m p s , J . , a n d D a m , C . ( 2 0 1 5 ) . Design and development o f two
component hydrogel ejector for three-dimensional cell growth. H o n o r s
S c h o l a r P h D . T h e s i s . U n i v e r s i t y o f C o n n e c t i c u t , M a n s f i e l d .
E a g l e , K . A . , a n d B a l i g a , R . R . ( 2 0 0 8 ) . Practical cardiology: evaluation and
treatment o f common cardiovascular disorders. ( 2 n d e d . ) . U n i t e d s t a t e :
L i p p i n c o t t W i l l i a m s & W i l k i n s .
E c k e r t , C . E . , F a n , R . , M i k u l i s , B . , B a r r o n , M . , C a r r u t h e r s , C . A . , F r i e b e , V . M . , e t a l .
( 2 0 1 3 ) . O n t h e b i o m e c h a n i c a l r o l e o f g l y c o s a m i n o g l y c a n s i n t h e a o r t i c h e a r t
v a l v e l e a f l e t . Acta Biomaterialia, 9 ( 1 ) , 4 6 5 3 - 4 6 6 0 .
179
E m m e r t , M . Y . , W e b e r , B . , B e h r , L . , S a m m u t , S . , F r a u e n f e l d e r , T . , W o l i n t , P . , e t a l .
( 2 0 1 3 ) . T r a n s c a t h e t e r a o r t i c v a l v e i m p l a n t a t i o n u s i n g a n a t o m i c a l l y o r i e n t e d ,
m a r r o w s t r o m a l c e l l - b a s e d , s t e n t e d , t i s s u e - e n g i n e e r e d h e a r t v a l v e s : t e c h n i c a l
c o n s i d e r a t i o n s a n d i m p l i c a t i o n s f o r t r a n s l a t i o n a l c e l l - b a s e d h e a r t v a l v e
c o n c e p t s . European Journal o f Cardio-Thoracic Surgery, 4 5 ( 1 ) , 6 1 - 6 8 .
E n g e l m a y r , G . C . , H i l d e b r a n d , D . K . , S u t h e r l a n d , F . W . , M a y e r , J . E . , a n d S a c k s , M .
S . ( 2 0 0 3 ) . A n o v e l b i o r e a c t o r f o r t h e d y n a m i c f l e x u r a l s t i m u l a t i o n o f t i s s u e
e n g i n e e r e d h e a r t v a l v e b i o m a t e r i a l s . Biomaterials, 2 4 ( 1 4 ) , 2 5 2 3 - 2 5 3 2 .
E n g e l m a y r , G . C . , R a b k i n , E . , S u t h e r l a n d , F . W . , S c h o e n , F . J . , M a y e r , J . E . , a n d
S a c k s , M . S . ( 2 0 0 5 ) . T h e i n d e p e n d e n t r o l e o f c y c l i c f l e x u r e i n t h e e a r l y i n
v i t r o d e v e l o p m e n t o f a n e n g i n e e r e d h e a r t v a l v e t i s s u e . Biomaterials, 26( 2 ) ,
1 7 5 - 1 8 7 .
E r b e t t a , C . D . A . C . , A l v e s , R . J . , R e s e n d e , J . M . , d e S o u z a F r e i t a s , R . F . , a n d d e
S o u s a , R . G . ( 2 0 1 2 ) . S y n t h e s i s a n d c h a r a c t e r i z a t i o n o f p o l y ( D , L - l a c t i d e - c o -
g l y c o l i d e ) c o p o l y m e r . Journal o f Biomaterials and Nanobiotechnology,
3 ( 0 2 ) , 2 0 8 - 2 1 5 .
E y k e n s , L . , D e S i t t e r , K . , D o t r e m o n t , C . , P i n o y , L . , a n d V a n d e r B r u g g e n , B . ( 2 0 1 6 ) .
C h a r a c t e r i z a t i o n a n d p e r f o r m a n c e e v a l u a t i o n o f c o m m e r c i a l l y a v a i l a b l e
h y d r o p h o b i c m e m b r a n e s f o r d i r e c t c o n t a c t m e m b r a n e d i s t i l l a t i o n .
Desalination, 392, 6 3 - 7 3 .
F a l k , V . , W a l t h e r , T . , S c h w a m m e n t h a l , E . , S t r a u c h , J . , A i c h e r , D . , W a h l e r s , T . , e t a l .
( 2 0 1 1 ) . T r a n s a p i c a l a o r t i c v a l v e i m p l a n t a t i o n w i t h a s e l f - e x p a n d i n g
a n a t o m i c a l l y o r i e n t e d v a l v e . European Heart Journal, 32( 7 ) , 8 7 8 - 8 8 7 .
F a l l a h i a r e z o u d a r , E . , A h m a d i p o u r r o u d p o s h t , M . , Y u s o f , N . M . , a n d I d r i s , A . ( 2 0 1 5 a ) .
F a b r i c a t i o n ( f e r r o f l u i d / p o l y v i n y l a l c o h o l ) m a g n e t i c n a n o f i b e r s v i a c o - a x i a l
e l e c t r o s p i n n i n g . Journal o f Dispersion Science and Technology, 3 6 ( 1 ) , 2 8 - 3 1 .
F a l l a h i a r e z o u d a r , E . , A h m a d i p o u r r o u d p o s h t , M . , Y u s o f , N . M . , a n d I d r i s , A . ( 2 0 1 5 b ) .
I n f l u e n c e o f p r o c e s s f a c t o r s o n d i a m e t e r o f c o r e ( y - F e 2 O 3 ) / s h e l l ( p o l y v i n y l
a l c o h o l ) s t r u c t u r e m a g n e t i c n a n o f i b e r s d u r i n g c o - a x i a l e l e c t r o s p i n n i n g .
International Journal o f Polymeric Materials and Polymeric Biomaterials,
6 4 ( 1 ) , 1 5 - 2 4 .
F a l l a h i a r e z o u d a r , E . , A h m a d i p o u r r o u d p o s h t , M . , I d r i s , A . , a n d Y u s o f , N . M . ( 2 0 1 5 c ) .
A r e v i e w o f : A p p l i c a t i o n o f s y n t h e t i c s c a f f o l d i n t i s s u e e n g i n e e r i n g h e a r t
v a l v e s . Materials Science and Engineering: C, 48 , 5 5 6 - 5 6 5 .
180
F a r i a s - M a n c i l l a , R . , E l i z a l d e - G a l i n d o , J . T . , V i g u e r a s - S a n t i a g o , E . , H e r n a n d e z -
E s c o b a r , C . A . , V e g a - R i o s , A . , a n d Z a r a g o z a - C o n t r e r a s , E . A . ( 2 0 1 6 ) .
S y n t h e s i s a n d c h a r a c t e r i z a t i o n o f p o l y a n i l i n e / m a g n e t i t e n a n o c o m p o s i t e .
International Journal o f Theoretical and Applied Nanotechnology, 4, 2 0 1
2 1 3 .
F i r o u z i , A . , D e l G a u d i o , C . , M o n t e s p e r e l l i , G . , a n d B i a n c o , A . ( 2 0 1 5 ) . E l e c t r o s p u n
p o l y m e r i c c o a t i n g s o n a l u m i n u m a l l o y a s a s t r a i g h t f o r w a r d a p p r o a c h f o r
c o r r o s i o n p r o t e c t i o n . Journal o f Applied Polymer Science, 1 3 2 ( 2 ) , 1 - 1 0 .
F i s c h e r - C r i p p s , A . C . ( 2 0 0 0 ) . Factors affecting nanoindentation test data.
Nanoindentation, p p . 6 1 - 8 2 , N e w Y o r k : S p r i n g e r .
F o n g , P . , S h i n ' o k a , T . , L o p e z - S o l e r , R . I . , a n d B r e u e r , C . ( 2 0 0 6 ) . T h e u s e o f p o l y m e r
b a s e d s c a f f o l d s i n t i s s u e - e n g i n e e r e d h e a r t v a l v e s . Progress in Pediatric
Cardiology, 2 1 ( 2 ) , 1 9 3 - 1 9 9 .
F r e e d , L . E . , G u i l a k , F . , G u o , X . E . , G r a y , M . L . , T r a n q u i l l o , R . , H o l m e s , J . W . , e t a l .
( 2 0 0 6 ) . A d v a n c e d t o o l s f o r t i s s u e e n g i n e e r i n g : s c a f f o l d s , b i o r e a c t o r s , a n d
s i g n a l i n g . Tissue Engineering, 1 2 ( 1 2 ) , 3 2 8 5 - 3 3 0 5 .
F r e n k e l , J . , a n d D o r f m a n , J . ( 1 9 3 0 ) . S p o n t a n e o u s a n d i n d u c e d m a g n e t i s a t i o n i n
f e r r o m a g n e t i c b o d i e s . Nature, 1 2 6 ( 3 1 7 3 ) , 2 7 4 - 2 7 5 .
F r e s e , L . , S a s s e , T . , S a n d e r s , B . , B a a i j e n s , F . , B e e r , G . M . , a n d H o e r s t r u p , S . P .
( 2 0 1 6 ) . A r e a d i p o s e - d e r i v e d s t e m c e l l s c u l t i v a t e d i n h u m a n p l a t e l e t l y s a t e
s u i t a b l e f o r h e a r t v a l v e t i s s u e e n g i n e e r i n g ? Journal o f Tissue Engineering
and Regenerative Medicine. D O I : 1 0 . 1 0 0 2 / t e r m . 2 1 1 8 .
F r e s h n e y , R . ( 2 0 0 0 ) . Culture o f animal cells: a manual o f basic techniques. (6th ed).
ISBN, 471348899, U n i t e d k i n g d o m : W i l e y O n l i n e L i b r a r y .
F r i e d , A . , a n d R i c h t e r , D . ( 2 0 0 6 ) . Infrared absorption spectroscopy. O x f o r d U K :
B l a c k w e l l P u b l i s h i n g .
G a l l y a m o v , M . O . , C h a s c h i n , I . S . , K h o k h l o v a , M . A . , G r i g o r e v , T . E . , B a k u l e v a , N .
P . , L y u t o v a , I . G . , e t a l . ( 2 0 1 4 ) . C o l l a g e n t i s s u e t r e a t e d w i t h c h i t o s a n
s o l u t i o n s i n c a r b o n i c a c i d f o r i m p r o v e d b i o l o g i c a l p r o s t h e t i c h e a r t v a l v e s .
S c h i m a n k e , G . , a n d M a r t i n , M . ( 2 0 0 0 ) . I n s i t u X R D s t u d y o f t h e p h a s e t r a n s i t i o n o f
n a n o c r y s t a l l i n e m a g h e m i t e ( y - F e 2 O 3 ) t o h e m a t i t e ( a - F e 2 O 3 ) . Solid State
Ionics, 136, 1 2 3 5 - 1 2 4 0 .
S c h o e n , F . ( 1 9 9 7 ) . A o r t i c v a l v e s t r u c t u r e - f u n c t i o n c o r r e l a t i o n s : r o l e o f e l a s t i c f i b e r s
n o l o n g e r a s t r e t c h o f t h e i m a g i n a t i o n . The Journal o f Heart Valve Disease,
6 ( 1 ) , 1 - 6 .
S c h o e n , F . J . , a n d L e v y , R . J . ( 1 9 9 9 ) . T i s s u e h e a r t v a l v e s : c u r r e n t c h a l l e n g e s a n d
f u t u r e r e s e a r c h p e r s p e c t i v e s . Journal o f Biomedical Materials Research,
4 7 ( 4 ) , 4 3 9 - 4 6 5 .
S c h o f e r , M . D . , R o e s s l e r , P . P . , S c h a e f e r , J . , T h e i s e n , C . , S c h l i m m e , S . , H e v e r h a g e n ,
J . T . , e t a l . ( 2 0 1 1 ) . E l e c t r o s p u n P L L A n a n o f i b e r s c a f f o l d s a n d t h e i r u s e i n
c o m b i n a t i o n w i t h B M P - 2 f o r r e c o n s t r u c t i o n o f b o n e d e f e c t s . PLoS One, 6 ( 9 ) ,
2 5 4 6 2 - 6 8 .
S e w e l l - L o f t i n , M . , C h u n , Y . W . , K h a d e m h o s s e i n i , A . , a n d M e r r y m a n , W . D . ( 2 0 1 1 ) .
E M T - i n d u c i n g b i o m a t e r i a l s f o r h e a r t v a l v e e n g i n e e r i n g : t a k i n g c u e s f r o m
d e v e l o p m e n t a l b i o l o g y . Journal o f Cardiovascular Translational Research,
4 ( 5 ) , 6 5 8 - 6 7 1 .
S h e i k h , F . A . , M a c o s s a y , J . , C a n t u , T . , Z h a n g , X . , H a s s a n , M . S . , S a l i n a s , M . E . , e t
a l . ( 2 0 1 5 ) . I m a g i n g , s p e c t r o s c o p y , m e c h a n i c a l , a l i g n m e n t a n d
b i o c o m p a t i b i l i t y s t u d i e s o f e l e c t r o s p u n m e d i c a l g r a d e p o l y u r e t h a n e
( C a r b o t h a n e ™ 3 5 7 5 A ) n a n o f i b e r s a n d c o m p o s i t e n a n o f i b e r s c o n t a i n i n g
m u l t i w a l l e d c a r b o n n a n o t u b e s . Journal o f the Mechanical Behavior o f
Biomedical Materials, 41, 1 8 9 - 1 9 8 .
S h e r i d a n , M . , S h e a , L . , P e t e r s , M . , a n d M o o n e y , D . ( 2 0 0 0 ) . B i o a b s o r b a b l e p o l y m e r
s c a f f o l d s f o r t i s s u e e n g i n e e r i n g c a p a b l e o f s u s t a i n e d g r o w t h f a c t o r d e l i v e r y .
Journal o f Controlled Release, 6 4 ( 1 ) , 9 1 - 1 0 2 .
S h i n o k a , T . , B r e u e r , C . K . , T a n e l , R . E . , Z u n d , G . , M i u r a , T . , M a , P . X . , e t a l . ( 1 9 9 5 ) .
T i s s u e e n g i n e e r i n g h e a r t v a l v e s : v a l v e l e a f l e t r e p l a c e m e n t s t u d y i n a l a m b
m o d e l . The Annals o f Thoracic Surgery, 60, 5 1 3 - 5 1 6 .
S i m o n , P . , K a s i m i r , M . , S e e b a c h e r , G . , W e i g e l , G . , U l l r i c h , R . , S a l z e r - M u h a r , U . , e t
a l . ( 2 0 0 3 ) . E a r l y f a i l u r e o f t h e t i s s u e e n g i n e e r e d p o r c i n e h e a r t v a l v e
S Y N E R G R A F T ® i n p e d i a t r i c p a t i e n t s . European Journal o f Cardio-thoracic
Surgery, 2 3 ( 6 ) , 1 0 0 2 - 1 0 0 6 .
195
S i n g h , B . , a n d N a n d a , B . ( 2 0 1 2 ) . S l i p d a m p i n g m e c h a n i s m i n w e l d e d s t r u c t u r e s
u s i n g r e s p o n s e s u r f a c e m e t h o d o l o g y . Experimental Mechanics, 5 2 ( 7 ) , 7 7 1
7 9 1 .
S o d i a n , R . , H o e r s t r u p , S . P . , S p e r l i n g , J . S . , D a e b r i t z , S . , M a r t i n , D . P . , M o r a n , A .
M . , e t a l . ( 2 0 0 0 ) . E a r l y i n v i v o e x p e r i e n c e w i t h t i s s u e - e n g i n e e r e d t r i l e a f l e t
h e a r t v a l v e s . Circulation, 1 0 2 ( 3 ) , 2 2 - 2 9 .
S o d i a n , R . , L e m k e , T . , L o e b e , M . , H o e r s t r u p , S . P . , P o t a p o v , E . V . , H a u s m a n n , H . , e t
a l . ( 2 0 0 1 ) . N e w p u l s a t i l e b i o r e a c t o r f o r f a b r i c a t i o n o f t i s s u e - e n g i n e e r e d
p a t c h e s . Journal o f Biomedical Materials Research, 5 8 ( 4 ) , 4 0 1 - 4 0 5 .
S o m b a t m a n k h o n g , K . , S a n c h a v a n a k i t , N . , P a v a s a n t , P . , a n d S u p a p h o l , P . ( 2 0 0 7 ) .
B o n e s c a f f o l d s f r o m e l e c t r o s p u n f i b e r m a t s o f p o l y ( 3 - h y d r o x y b u t y r a t e ) , p o l y
( 3 - h y d r o x y b u t y r a t e - c o - 3 - h y d r o x y v a l e r a t e ) a n d t h e i r b l e n d . Polymer, 4 8 ( 5 ) ,
1 4 1 9 - 1 4 2 7 .
S o o d , A . , A r o r a , V . , S h a h , J . , K o t n a l a , R . , a n d J a i n , T . K . ( 2 0 1 6 ) . A s c o r b i c a c i d -
m e d i a t e d s y n t h e s i s a n d c h a r a c t e r i s a t i o n o f i r o n o x i d e / g o l d c o r e - s h e l l
n a n o p a r t i c l e s . Journal o f Experimental Nanoscience, 1 1 ( 5 ) , 3 7 0 - 3 8 2 .
S t e l l a , J . A . , L i a o , J . , a n d S a c k s , M . S . ( 2 0 0 7 ) . T i m e - d e p e n d e n t b i a x i a l m e c h a n i c a l
b e h a v i o r o f t h e a o r t i c h e a r t v a l v e l e a f l e t . Journal o f Biomechanics, 4 0 ( 1 4 ) ,
3 1 6 9 - 3 1 7 7 .
S t e l l a , J . A . , a n d S a c k s , M . S . ( 2 0 0 7 ) . O n t h e b i a x i a l m e c h a n i c a l p r o p e r t i e s o f t h e
l a y e r s o f t h e a o r t i c v a l v e l e a f l e t . Journal o f Biomechanical Engineering,
129( 5 ) , 7 5 7 - 7 6 6 .
S t o u t , K . K . , a n d V e r r i e r , E . D . ( 2 0 0 9 ) . A c u t e v a l v u l a r r e g u r g i t a t i o n . Circulation,
1 1 9 ( 2 5 ) , 3 2 3 2 - 3 2 4 1 .
S t r a d i n s , P . , L a c i s , R . , O z o l a n t a , I . , P u r i n a , B . , O s e , V . , F e l d m a n e , L . , e t a l . ( 2 0 0 4 ) .
C o m p a r i s o n o f b i o m e c h a n i c a l a n d s t r u c t u r a l p r o p e r t i e s b e t w e e n h u m a n a o r t i c
a n d p u l m o n a r y v a l v e . European Journal o f Cardio-thoracic Surgery, 2 6 ( 3 ) ,
6 3 4 - 6 3 9 .
S u l t a n a , N . a n d M . W a n g , ( 2 0 1 2 ) . P H B V / P L L A - b a s e d c o m p o s i t e s c a f f o l d s
f a b r i c a t e d u s i n g a n e m u l s i o n f r e e z i n g / f r e e z e - d r y i n g t e c h n i q u e f o r b o n e t i s s u e
e n g i n e e r i n g : s u r f a c e m o d i f i c a t i o n a n d i n v i t r o b i o l o g i c a l e v a l u a t i o n .
Biofabrication, 2 0 1 2 . 4 ( 1 ) , 0 1 5 0 0 3 .
196
S u n g , Y . K . , A h n , B . W . , a n d K a n g , T . J . ( 2 0 1 2 ) . M a g n e t i c n a n o f i b e r s w i t h c o r e
( F e 3 O 4 n a n o p a r t i c l e s u s p e n s i o n ) / s h e a t h ( p o l y e t h y l e n e t e r e p h t h a l a t e ) s t r u c t u r e
f a b r i c a t e d b y c o a x i a l e l e c t r o s p i n n i n g . Journal o f Magnetism and Magnetic
Materials, 3 2 4 ( 6 ) , 9 1 6 - 9 2 2 .
S w a n s o n , W . M . , a n d C l a r k , R . E . ( 1 9 7 4 ) . D i m e n s i o n s a n d g e o m e t r i c r e l a t i o n s h i p s o f
t h e h u m a n a o r t i c v a l u e a s a f u n c t i o n o f p r e s s u r e . Circulation Research, 35( 6 ) ,
8 7 1 - 8 8 2 .
T a h e r k h a n i , S . , a n d M o z t a r z a d e h , F . ( 2 0 1 6 ) . F a b r i c a t i o n o f a p o l y ( e -
c a p r o l a c t o n e ) / s t a r c h n a n o c o m p o s i t e s c a f f o l d w i t h a s o l v e n t - c a s t i n g / s a l t -
l e a c h i n g t e c h n i q u e f o r b o n e t i s s u e e n g i n e e r i n g a p p l i c a t i o n s . Journal o f
AppliedPolymer Science, D O I : 1 0 . 1 0 0 2 / a p p . 4 3 5 2 3 .
T a l m a n , E . , a n d B o u g h n e r , D . ( 1 9 9 6 ) . I n t e r n a l s h e a r p r o p e r t i e s o f f r e s h p o r c i n e
a o r t i c v a l v e c u s p s : i m p l i c a t i o n s f o r n o r m a l v a l v e f u n c t i o n . The Journal o f
Heart Valve Disease, 5 ( 2 ) , 1 5 2 - 1 5 9 .
T a n , A . , a n d H o l t , D . ( 1 9 7 6 ) . T h e e f f e c t s o f s t e r i l i z a t i o n a n d s t o r a g e t r e a t m e n t s o n
t h e s t r e s s - s t r a i n b e h a v i o r o f a o r t i c v a l v e l e a f l e t s . The Annals o f Thoracic
Surgery, 2 2 ( 2 ) , 1 8 8 - 1 9 4 .
T a n a k a , K . , S a t a , M . , F u k u d a , D . , S u e m a t s u , Y . , M o t o m u r a , N . , T a k a m o t o , S . , e t a l .
( 2 0 0 5 ) . A g e - a s s o c i a t e d a o r t i c s t e n o s i s i n a p o l i p o p r o t e i n E - d e f i c i e n t m i c e .
Journal o f the American College o f Cardiology, 4 6 ( 1 ) , 1 3 4 - 1 4 1 .
T a r a n , M . , a n d A g h a i e , E . ( 2 0 1 5 ) . D e s i g n i n g a n d o p t i m i z a t i o n o f s e p a r a t i o n p r o c e s s
o f i r o n i m p u r i t i e s f r o m k a o l i n b y o x a l i c a c i d i n b e n c h - s c a l e s t i r r e d - t a n k
r e a c t o r . Applied Clay Science, 107, 1 0 9 - 1 1 6 .
T a r t a j , P . , d e l P u e r t o M o r a l e s , M . , V e i n t e m i l l a s - V e r d a g u e r , S . , G o n z a l e z - C a r r e n o ,
T . , a n d S e r n a , C . J . ( 2 0 0 3 ) . T h e p r e p a r a t i o n o f m a g n e t i c n a n o p a r t i c l e s f o r
a p p l i c a t i o n s i n b i o m e d i c i n e . Journal o f Physics D: Applied Physics, 36( 1 3 ) ,
1 8 2 - 1 9 7 .
T a y l o r , P . , A l l e n , S . , D r e g e r , S . , a n d Y a c o u b , M . ( 2 0 0 2 ) . H u m a n c a r d i a c v a l v e
i n t e r s t i t i a l c e l l s i n c o l l a g e n s p o n g e : a b i o l o g i c a l t h r e e - d i m e n s i o n a l m a t r i x f o r
t i s s u e e n g i n e e r i n g . The Journal o f Heart Valve Disease, 1 1 ( 3 ) , 2 9 8 - 3 0 6 .
T a y l o r , P . M . , C a s s , A . E . , a n d Y a c o u b , M . H . ( 2 0 0 6 ) . E x t r a c e l l u l a r m a t r i x s c a f f o l d s
f o r t i s s u e e n g i n e e r i n g h e a r t v a l v e s . Progress in Pediatric Cardiology, 2 1 ( 2 ) ,
2 1 9 - 2 2 5 .
197
T e e b k e n , O . , B a d e r , A . , S t e i n h o f f , G . , a n d H a v e r i c h , A . ( 2 0 0 0 ) . T i s s u e e n g i n e e r i n g
o f v a s c u l a r g r a f t s : h u m a n c e l l s e e d i n g o f d e c e l l u l a r i s e d p o r c i n e m a t r i x .
European Journal o f Vascular and Endovascular Surgery, 1 9 ( 4 ) , 3 8 1 - 3 8 6 .
T e o , W . , a n d R a m a k r i s h n a , S . ( 2 0 0 6 ) . A r e v i e w o n e l e c t r o s p i n n i n g d e s i g n a n d
n a n o f i b r e a s s e m b l i e s . Nanotechnology, 1 7 ( 1 4 ) , 8 9 - 9 3 .
T h a d a v i r u l , N . , P a v a s a n t , P . , a n d S u p a p h o l , P . ( 2 0 1 4 ) . D e v e l o p m e n t o f
p o l y c a p r o l a c t o n e p o r o u s s c a f f o l d s b y c o m b i n i n g s o l v e n t c a s t i n g , p a r t i c u l a t e
l e a c h i n g , a n d p o l y m e r l e a c h i n g t e c h n i q u e s f o r b o n e t i s s u e e n g i n e e r i n g .
Journal o f Biomedical Materials Research Part A, 1 0 2 ( 1 0 ) , 3 3 7 9 - 3 3 9 2 .
T h o m , T . , H a a s e , N . , R o s a m o n d , W . , H o w a r d , V . J . , R u m s f e l d , J . , M a n o l i o , T . , e t a l .
( 2 0 0 6 ) . H e a r t d i s e a s e a n d s t r o k e s t a t i s t i c s - 2 0 0 6 u p d a t e a r e p o r t f r o m t h e
A m e r i c a n H e a r t A s s o c i a t i o n S t a t i s t i c s C o m m i t t e e a n d S t r o k e S t a t i s t i c s
S u b c o m m i t t e e . Circulation, 1 1 3 ( 6 ) , 8 5 - 1 5 1 .
T h u b r i k a r , M . , P i e p g r a s s , W . C . , D e c k , J . D . , a n d N o l a n , S . P . ( 1 9 8 0 ) . S t r e s s e s o f
n a t u r a l v e r s u s p r o s t h e t i c a o r t i c v a l v e l e a f l e t s i n v i v o . The Annals o f Thoracic
Surgery, 3 0 ( 3 ) , 2 3 0 - 2 3 9 .
T h u b r i k a r , M . J . ( 1 9 8 9 ) . The aortic valve: C R C p r e s s , N e w Y o r k : U n i t e d s t a t e .
T h u b r i k a r , M . J . , N o l a n , S . P . , A o u a d , J . , a n d D e c k , J . D . ( 1 9 8 6 ) . S t r e s s s h a r i n g
b e t w e e n t h e s i n u s a n d l e a f l e t s o f c a n i n e a o r t i c v a l v e . The Annals o f Thoracic
Surgery, 42( 4 ) , 4 3 4 - 4 4 0 .
T i l l q u i s t , M . N . , a n d M a d d o x , T . M . ( 2 0 1 1 ) . C a r d i a c c r o s s r o a d s : d e c i d i n g b e t w e e n
m e c h a n i c a l o r b i o p r o s t h e t i c h e a r t v a l v e r e p l a c e m e n t . Patient Prefer
Adherence, 5, 9 1 - 9 9 .
T o r r i c e l l i , P . , G i o f f r e , M . , F i o r a n i , A . , P a n z a v o l t a , S . , G u a l a n d i , C . , F i n i , M . , e t a l .
( 2 0 1 4 ) . C o - e l e c t r o s p u n g e l a t i n - p o l y ( L - l a c t i c a c i d ) s c a f f o l d s : m o d u l a t i o n o f
m e c h a n i c a l p r o p e r t i e s a n d c h o n d r o c y t e r e s p o n s e a s a f u n c t i o n o f
c o m p o s i t i o n . Materials Science and Engineering: C, 36, 1 3 0 - 1 3 8 .
T o r t o r a , G . , a n d G r a b o w s k i , S . ( 2 0 0 0 ) . Measuring blood pressure. Principles o f
Anatomy and Physiology, ( 9 th e d . ) N e w Y o r k : J o h n W i l e y & S o n s C o .
T s e n g , Y . T . , C h a p r o n , J . , T h o m p s o n , R . , D o n y i a , M . , S o h i e r , J . , A g i u b , H . , e t a l .
( 2 0 1 6 ) . The U s e o f c t a n d r a p i d p r o t o t y p i n g t o p r o d u c e a n e x a c t r e p l i c a o f t h e
n o r m a l h u m a n a o r t i c r o o t f o r t i s s u e e n g i n e e r i n g . Paper presented at the
Qatar Foundation Annual Research Conference Proceedings, HBOP3286.
198
T u l e t a , I . , A l G h a d d i o u i , A . K . , B a u r i e d e l , G . , W e r n e r t , N . , P r e u s s e , C . J . , W e l z , A . ,
e t a l . ( 2 0 1 3 ) . T h e i m b a l a n c e b e t w e e n p r o l i f e r a t i o n a n d a p o p t o s i s c o n t r i b u t e s
t o d e g e n e r a t i o n o f a o r t i c v a l v e s a n d b i o p r o s t h e s e s . Cardiology Journal,
2 0 ( 3 ) , 2 6 8 - 2 7 6 .
V a c a n t i , J . P . , M o r s e , M . A . , S a l t z m a n , W . M . , D o m b , A . J . , P e r e z - A t a y d e , A . , a n d
L a n g e r , R . ( 1 9 8 8 ) . S e l e c t i v e c e l l t r a n s p l a n t a t i o n u s i n g b i o a b s o r b a b l e a r t i f i c i a l
p o l y m e r s a s m a t r i c e s . Journal o f Pediatric Surgery, 2 3 ( 1 ) , 3 - 9 .
V a n D o o r n , C . ( 2 0 0 2 ) . T h e u n n a t u r a l h i s t o r y o f t e t r a l o g y o f F a l l o t : s u r g i c a l r e p a i r i s
n o t a s d e f i n i t i v e a s p r e v i o u s l y t h o u g h t . Heart, 8 8 ( 5 ) , 4 4 7 - 4 4 8 .
V a n L i e s h o u t , M . , V a z , C . , R u t t e n , M . , P e t e r s , G . , a n d B a a i j e n s , F . ( 2 0 0 6 ) .
E l e c t r o s p i n n i n g v e r s u s k n i t t i n g : t w o s c a f f o l d s f o r t i s s u e e n g i n e e r i n g o f t h e
a o r t i c v a l v e . Journal o f Biomaterials Science, Polymer Edition, 1 7 ( 1 ) , 7 7 - 8 9 .
V a z , C . , V a n T u i j l , S . , B o u t e n , C . , a n d B a a i j e n s , F . ( 2 0 0 5 ) . D e s i g n o f s c a f f o l d s f o r
b l o o d v e s s e l t i s s u e e n g i n e e r i n g u s i n g a m u l t i - l a y e r i n g e l e c t r o s p i n n i n g
t e c h n i q u e . Acta Biomaterialia, 1( 5 ) , 5 7 5 - 5 8 2 .
V a z q u e z , M . , D e l g a d o , R . , a n d C a s t r o , A . J . ( 2 0 0 9 ) . M o d e l l i n g o f t h e e n z y m a t i c
h y d r o l y s i s o f p o t a t o ( S o l a n u m t u b e r o s u m ) u s i n g r e s p o n s e s u r f a c e
m e t h o d o l o g y . Starch-Starke, 6 1 ( 1 0 ) , 6 0 1 - 6 0 9 .
V e s e l y , I . , a n d B o u g h n e r , D . R . ( 1 9 8 5 ) . A m u l t i p u r p o s e t i s s u e b e n d i n g m a c h i n e .
Journal o f Biomechanics, 1 8 ( 7 ) , 5 1 1 - 5 1 3 .
V e s e l y , I . , a n d B o u g h n e r , D . ( 1 9 8 9 ) . A n a l y s i s o f t h e b e n d i n g b e h a v i o u r o f p o r c i n e
x e n o g r a f t l e a f l e t s a n d o f n a t u r a l a o r t i c v a l v e m a t e r i a l : b e n d i n g s t i f f n e s s ,
n e u t r a l a x i s a n d s h e a r m e a s u r e m e n t s . Journal o f Biomechanics, 22( 6 ) , 6 5 5
6 7 1 .
W a l l i n , R . F . , a n d A r s c o t t , E . ( 1 9 9 8 ) . A p r a c t i c a l g u i d e t o I S O 1 0 9 9 3 - 5 : C y t o t o x i c i t y .
Medical Device and Diagnostic Industry, 20, 9 6 - 9 8 .
W a n g , L . , Y a n g , S . , W a n g , J . , W a n g , C . , a n d C h e n , L . ( 2 0 1 1 ) . F a b r i c a t i o n o f
s u p e r h y d r o p h o b i c T P U f i l m f o r o i l - w a t e r s e p a r a t i o n b a s e d o n
e l e c t r o s p i n n i n g r o u t e . Materials Letters, 6 5 ( 5 ) , 8 6 9 - 8 7 2 .
W a n g , X . , L i , X . , a n d Y o s t , M . J . ( 2 0 0 5 ) . M i c r o t e n s i l e t e s t i n g o f c o l l a g e n f i b r i l f o r
c a r d i o v a s c u l a r t i s s u e e n g i n e e r i n g . Journal o f Biomedical Materials Research
Part A, 7 4 ( 2 ) , 2 6 3 - 2 6 8 .
W a n g , Y . , A m e e r , G . A . , S h e p p a r d , B . J . , a n d L a n g e r , R . ( 2 0 0 2 ) . A t o u g h
b i o d e g r a d a b l e e l a s t o m e r . Nature Biotechnology, 20( 6 ) , 6 0 2 - 6 0 6 .
199
W a n g , Z . , B i , H . , L i u , J . , S u n , T . , a n d W u , X . ( 2 0 0 8 ) . M a g n e t i c a n d m i c r o w a v e
a b s o r b i n g p r o p e r t i e s o f p o l y a n i l i n e / y - F e 2 O 3 n a n o c o m p o s i t e . Journal o f