Fabrication, in vitro, in vivo evaluation of hybrid biopolymers for artificial soft and hard tissue aplication

Doctorate Thesis Fabrication, In-vitro, In-vivo Evaluation of Hybrid Biopolymers for Artificial Soft and Hard Tissue Application 2012 08 College of Medicine, SoonChunHyang University Biomedical Engineering & Materials, Nguyen Thi Hiep Fabrication, In-vitro, In-vivo Evaluation of Hybrid Biopolymers for Artificial Soft and Hard Tissue Application Advisor: Professor Lee Byong-Taek Dissertation submitted for the degree of Doctor of Philosophy 2012 07 College of Medicine, SoonChunHyang University Biomedical Engineering & Materials, Nguyen Thi Hiep Acknowledgements First of all I would like to express my profound gratitude and earnest reverence to Dr Byong-Taek Lee, Professor, Department of Biomedical Engineering and Materials, School of Medicine, Soonchunhyang University, Cheonan, Korea for his enthusiastic guidance, constructive and creative suggestions and continuous supervision throughout the progress of this work I earnestly acknowledge that without his dynamic and encouragement, I could never be completed my thesis and matured in my works as it is now I would like to express my heartiest gratitude and thanks to professor Young-Ki Min and professor Hun-Mo Yang, Department of Physiology, SoonChunHyang University; for their kind and sage advices and encouragements to continue the work and for their enormous support during my work While doing the work I received help and encouragement not only in my academic matter but also in my personal life from a number of people; I owe my thanks to my faithful husband, Mr Dao Van Hoa, always stands side-by-side and supports the spiritual atmosphere for me I thank all of my department members for their effort and guidance in my academic life I also wish to thank Mr S-W Kim, Mr DV Quang, Dr KP Rajat, and Ms Lee for their kind supports It is my pleasure to express my gratitude to Mr D-W Jang, Mr DV Tuyen, Mr.TV Viet, Dr NTB Linh, Ms NT Phuong, Mr TQ Bao, Ms YH Kim, Dr KS Swapan, Ms H-J Hong, Mr M-S Kim, Ms S-H Lim, Mr M Dibakar, Mr DNh Subrato, Ms S So-Ra, Ms Rose-Ann F, Ms J-H Kim, Mr Alexandar S, Ms.Celine A, Mr Nathaiel C, Mr Andrew RP for their help I would like to iv extend my thankful gratitude to Prof Kap-Ho Lee, School of Advanced Materials Engineering, Chungnam National University, and Dr S-J Lee, Department of Thoracic and Cardiovascular Surgery, Cheonan Hospital, Soonchunhyang University, Cheonan, 330-090, Korea, for their valuable assistance And, I am deeply indebted to my grand-fathers, my grand-mother, my father, my mother, my father-in-law, my mother-in-law, my brothers, my sisters, my brothers-in-law, my sisters-in-law, my nieces and my nephew for their encouragement, patience and love without which it was impossible to achieve all that I have done Cheonan, South Korea, July 2012 Nguyen Thi Hiep v Dedication To my parents vi Contents Acknowledgement iv Dedication vi List of Tables ix List of Figures x xvii Abstract Chapter 1- General Introduction 1.1 About Tissue Engineering 1.2 The ideal of Biomaterials 1.3 Objectives of this dissertation Chapter 2- Tissue Engineering of Skin 2.1 Introduction 2.2 Study I: Nano Ag Loaded PVA Nano-Fibrous Mats for Skin Applications 2.2.1 Introduction 2.2.2 Materials and methods 2.2.3 Results and Discussion 2.2.4 Conclusion 2.3 Study II: Fabrication of Cross-linked Nano-fibrous Chitosan Membranes Using an Electro-spinning Process and Their Biocompatibility Evaluation 2.3.1 Introduction 15 16 16 2.3.2 Materials and methods 17 2.3.3 Results and Discussion 19 2.3.4 Conclusion 2.4 Study III: Fabrication and Characterization of Cross-linked Gelatin Electro-spun Nano-fibers 2.4.1 Introduction 24 25 25 2.4.2 Materials and methods 26 2.4.3 Results and Discussion 28 2.4.4 Conclusion 34 Chapter 3- Tissue Engineering of Blood Vessel 35 3.1 Introduction 3.2 Study I: The effect of cross-linking on the microstructure, mechanical properties and biocompatibility of electrospun polycaprolactonegelatin/PLGA-gelatin/PLGA-chitosan hybrid composite 3.2.1 Introduction 35 36 36 3.2.2 Materials and Methods 37 3.2.3 Results and Discussion 40 3.2.4 Conclusion 48 3.3 Study II: Characterizes and In vitro Study of Tubular Electrospun vii 49 PU/PCL for Artificial Blood Vessel Application 3.3.1 Introduction 49 3.3.2 Materials and Methods 50 3.3.3 Results and Discussion 54 3.3.4 Conclusion 3.4 Study III: Hemocompatibility Testing of Conjugated Linoleic Acid Loaded Electrospun Polycaptrolactone/Polyurethane Membrane 3.4.1 Introduction 61 62 62 3.4.2 Materials and Methods 63 3.4.3 Results and Discussion 66 3.4.4 Conclusion 70 Chapter 4- Tissue Engineering of Bone 71 4.1 Introduction 4.2 Study I: In-Vitro and In-Vivo Studies of rhBMP2-Coated PS/PCL Fibrous Scaffolds for Bone Regeneration 4.2.1 Introduction 71 73 73 4.2.2 Materials and Methods 74 4.2.3 Results and Discussion 78 4.2.4 Conclusion 4.3 Study II: Distribution of BCP in PCL/PLGA Porous Scaffold to Enhance Osteoblastic Differentiation of human mesenchymal stem cell and Osteogenesis in Rabbit Defect Model 4.3.1 Introduction 88 89 89 4.3.2 Materials and Methods 90 4.3.3 Results and Discussion 93 4.3.4 Conclusion 4.4 Study III: Comparison of the effect osteoinductive (RGD, BMP2) and osteoconductive (BCP) agents to bone remodeling of poly vinylalcohol/gelatin hydrogel matrices 4.4.1 Introduction 100 101 101 4.4.2 Materials and Methods 102 4.4.3 Results and Discussion 107 4.4.4 Conclusion 121 Chapter 5- General Conclusion 122 References 123 Research achievements 142 viii List of Tables Chapter Study I: Nano Ag Loaded PVA Nano-Fibrous Mats for Skin Applications Table Zone of inhibition test from the disc diffusion test 13 Chapter Study I: The effect of cross-linking on the microstructure, mechanical properties and biocompatibility of electrospun polycaprolactonegelatin/PLGA-gelatin/PLGA-chitosan hybrid composite Table The parameters used for fabricating chitosan, PLGA, gelatin and PCL fibrous scaffolds 38 Chapter Study III: Comparison of the effect osteoinductive (RGD, BMP2) and osteoconductive (BCP) agents to bone remodeling of poly vinylalcohol/gelatin hydrogel matrices Table Characterization and properties of hydrogels ix 107 List of Figures Chapter Fig (A) The tissue engineering cycle, using autologous cells 1: A small number of cells are removed from the body 2: They are screened for phenotype and increased in number through proliferation 3: These cells are seeded onto porous scaffolds together with growth factors to enhance proliferation 4: The seeded scaffolds are placed in culture to further increase cell number 5: Finally, the regenerated tissue is implanted into the site of damage to integrate with the natural tissue (B) Example of tissue-engineered cartilage in the shape of a human ear Fig Different scaffold architectures provide cells with different topological cues.(A) A foamed or salt leached scaffold with large interconnected pores to permits cell ingrowth presents cells with a large, continuous surface area for attachment (B) Micro-fibrous scaffolds can be made to have greater porosity Where there is a large gap between fibres, focal adhesion placement guides cells to elongating along the fibre and this may restrict the contact with cells on different fibres (C) Nanofibre scaffolds have a larger surface area in relation to mass and can be fabricated with high porosity Focal adhesion size is limited by the fibre diameter, reducing a cell’s ability to develop a strong cytoskeleton such that cells may remain more rounded and stationary within the scaffold Chapter Fig schematically process of tissue-engineered skin Study I: Nano Ag Loaded PVA Nano-Fibrous Mats for Skin Applications Fig SEM micrographs of Ag NPs loaded electro-spun PVA mats with microwave 60 seconds (a), 90 seconds (b); c) and d) are EDS profile on the large area of a) and b) Fig.2 UV-Vis absorption spectra of PVA/Ag solution with different microwave irradiation time Fig XRD curves of AgNO3 loaded electrospun PVA mat and Ag NPs loaded electrospun PVA mat Fig SEM micrographs Ag NPs loaded electrospun PVA mats with microwave 60 seconds at 80°C (a), 120 °C (c), and 150 °C (e); with 90 seconds at 150 °C (g); (b), (d) (f) and (h) are enlarge image of (a), (c) (e) and (h) Fig.5 TEM and HRTEM image of Ag NPs loaded electrospun PVA nano-fiber with 60 seconds microwave irradiation and heat at 150 °C Fig FT-IR curves of PVA powder, Ag NPs loaded electro-spun PVA mat before and after heat at 150 °C Fig DSC curves of PVA powder (a), electro-spun PVA (b), Ag NPs loaded electro-spun PVA before heat treatment (c) and after heat treatment (d) Fig Comparison of the inhibition zone test between a, e) pure PVA mat; b, f) PVA-Ag mat; c, g) PVA-Ag NPs-2 (120℃); d, h) PVA–Ag NPs-2 (150℃) The photographs of the disk sensitivity test for E coli (a, b, c, d) and S aureus (e, f, g, h) Fig Tensile strength curves of electro-spun PVA, Ag NPs loaded electro-spun PVA before and after heat treatment Study II: Fabrication of Cross-linked 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Mann, B.K., R.H Schmedlen, and J.L West, Tethered-TGF-β increases extracellular matrix production of vascular smooth muscle cells Biomaterials, 2001 22(5): p 439-444 Halstenberg, S., et al., Biologically Engineered Protein-graftPoly(ethylene glycol) Hydrogels:  A Cell Adhesive and PlasminDegradable Biosynthetic Material for Tissue Repair Biomacromolecules, 2002 3(4): p 710-723 Hari, P.R and K Sreenivasan, Preparation of polyvinyl alcohol hydrogel through the selective complexation of amorphous phase Journal of Applied Polymer Science, 2001 82(1): p 143-149 Yamamoto, M., Y Takahashi, and Y Tabata, Enhanced Bone Regeneration at a Segmental Bone Defect by Controlled Release of Bone Morphogenetic Protein-2 from a Biodegradable Hydrogel Tissue Engineering, 2006 12(5): p 1305-1311 Su, J., et al., Enhanced compatibilization and orientation of polyvinyl alcohol/gelatin composite fibers using carbon nanotubes Journal of Applied Polymer Science, 2008 107(6): p 4070-4075 Yang, D., Y Li, and J 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Kap-Ho Lee and Byong-Taek Lee BCP Loading on PCL/ PLGA Membranes for Improved Tensile Strength, in vitro Biocompatibility and in vivo Tissue Regeneration J Mater Sci: Mater Med Thi-Hiep Nguyen, So-Ra So, Hyung-Seok Seo, Young-Ki Min and Byong-Taek Lee Novel Injectable Bone Substitute Porous Poly (lactic-co- glycolic acid) Microspheres/Biphasic Calcium Phosphates Sci Technol Adv Mater Submitted Thi-Hiep Nguyen, Trinh Quang Bao, Ihho Park and Byong-Taek Lee A Novel Fibrous Scaffold Composed of Electrospun Porous Poly(ε-caprolactone) (PCL) Fibers for Bone Tissue Engineering Journal of Biomaterials Application Submitted Thi-Hiep Nguyen, Young-Ki Min and Byong-Taek Lee Distribution of BCP in PCL/PLGA Porous Scaffold to Enhance Osteoblastic Differentiation of Human Mesenchymal Stem Cell and Osteogenesis in Rabbit Defect Mode.l J of Biomaterials Application Thi-Hiep Nguyen, Young-Ki Min and Byong-Taek Lee In vitro and in vivo evaluation of the poly vinylalcohol gelatin hydrogel with varied growth factors in bone applications Biomaterials Thi-Hiep Nguyen, and Lee Byong Taek Investigation of Cross-linked Polyvinyl Alcohol-Gelatin Hydrogel for Bone Regeneration: Fabrication, Characterization, In Vitro and In Vivo Studies Submitted Thi-Hiep Nguyen and Byong-Taek Lee A Hybrid Electrospun PU/PCL Scaffold Satisfied the Requirements of Blood Vessel Prosthesis as Mechanical Properties, Pore Size and Excellent Biocompatibility , Submitted Thi-Hiep Nguyen and Byong-Taek Lee Evaluation of Platelet Adhesion and Protein Absorption on Linoleic Acid Loaded-Electrospun PCL/PU Mat for Artificial Blood Vessel Applications J BMR: Part B - Applied Biomaterials Submitted 10 Thi-Hiep Nguyen and Byong-Taek Lee The effect of cross-linking on the microstructure, mechanical properties and biocompatibility of electrospun polycaprolactone–gelatin/PLGA–gelatin/ PLGA–chitosan hybrid composite Sci Technol Adv Mater 13 (2012) 035002 (11pp) 11 Dong-Woo Jang, Thi-Hiep Nguyen, Swapan Kumar Sarkar, and Byong-Taek Lee Science and Technology of Advanced Materials Sintering mperature effect on the Microstructure of multilayered HAp-ZrO2 artificial bone by microwave sintering and its detailed in-vitro study Sci Technol Adv Mater Accepted 12 Rose Ann Franco, Nguyen Thi Hiep and Byong-Taek Lee Preparation and Characterization of Electrospun PCL/PLGA Membranes and Chitosan-Gelatin Hydrogels for Skin Bioengineering Applications J Mater Sci: Mater Med (2011) 22:2207–2218 13 Trinh-Quang Bao, Thi-Hiep Nguyen, Yang-Hee Kim, Hun-Mo Yang and ByongTaek Lee Fabrication and Characterization of Porous Poly(lactic-co-glycolic acid)(PLGA) Microspheres for Use as a Drug Delivery System J Mater Sci 46 (2010) 2510-2517 142 14 Thi-Hiep Nguyen, Seong-Jin Lee, Young-Ki Min and Byong-Taek Lee Fabrication of Cross-linked Nano-fibrous Chitosan Maembranes and Their Biocompatibility Evaluation J Mater Res Sci Vol 21, 2011 15 Thi-Hiep Nguyen, Byong-Taek Lee One Step for Fabricating Cross-linked Electrospun Gelatin Fibers Oct 2010 JBiSE (2010) 1117-1124 16 Thi-Hiep Nguyen, Kim Young-Hee, Ho-Yeon Song and Byong-Taek Lee Nano Ag Loaded PVA Nano-Fibrous Mats for Skin Applications J Bio Mater Res: Appli Biomater 96 B (2010) 225-233 17 Thi-Hiep Nguyen, Kap-Ho Lee, Byong-Taek Lee Fabrication of Ag Nano particles Dispersed in PVA Nanowires Mats by Microwave Irradiation and Electro-spinning Mater Sci Eng C 30 (2010) 944–950 18 Thi-Hiep Nguyen, Byong-Taek Lee Fabrication of Artificial Bone by the Combination of Electrospinning, Extrusion and Slurry Processes Mater Sci For Vols 654-656 (2010) pp 2233-2236 19 Nguyen Thi Hiep, Byong-Taek Lee Electro-spinning of PLGA/PCL blends for tissue engineering and their biocompatibility J Mater Sci: Mater Med 21 (2010) 1969-1978 PATENTS Thi Hiep Nguyen and Lee Byong Taek Investigation of Cross-linked Polyvinyl Alcohol-Gelatin Hydrogel for Bone Regeneration: Fabrication, Characterization, In Vitro and In Vivo Studies Thi-Hiep Nguyen, Dong-Woo Jang, Young-Ki Min, Ho-Yeon Song and ByongTaek Lee Fabrication of Artificial Bone by the Combination of Electro-spinning, Extrusion and Slurry Processes Thi-Hiep Nguyen, Hong Hyun Jin and Lee Byong Taek Nano Ag Loaded PVA Nano-Fibrous Mats for Skin Applications Thi-Hiep Nguyen, Hong Hyun Jin and Lee Byong Taek Electro-spinning of PLGA/PCL Blends for Tissue Engineering and Their Biocompatibility INTERNATIONAL CONFERENCES Thi-Hiep Nguyen and Lee Byong Taek In vitro and In vivo Study og the Modification of Poly vinyl alcohole/Gelatin Loading BCP with Collagen for Bone Application TERMIS (Singapore), 2011 Thi-Hiep Nguyen, Hun-Mo Yang, Young-Ki Min and Byong-Taek Lee Fabrication of PCL/PLGA- 3-D Scaffolds Fabricated by Slurry Process for Bone Tissue Engineering: Characterization, Properties and Biocompatibility ABC (Korea), 2011 SADIASA Alexander, Nguyen Thi Hiep and Byong Taek Lee, Preparation and Characterization of Novel PLLA-PCL 3-D Scaffolds by Salt Leaching Method for Bone Tissue Engineering Applications, ABC (Korea), 2011 Rose Ann Fransco, Nguyen Thi Hiep and Lee Byong Taek, In vitro and In vivo Biocompatibility of Novel Electrospun PVPA/PVA Nanofiber Membranes for Tissue Engineering Applications, ABC (Korea), 2011 Nguyen Thi Hiep, Byong-Taek Lee Fabrication of Artificial Bone by the Combination of Electrospinning, Extrusion and Slurry Processes PRICM 7, Cairns (Australia), 2010 Nguyen Thi Hiep, Byong-Taek Lee Evaluation of Platelet Adhesion and Protein Absorption on Linoleic Acid Loaded Electrospun PCL/PU Mat for Artificial Blood Vessel Applications MFMS, ChungJu (Korea), 2010 DOMESTIC CONFERENCES Alexander Sadiasaa, Thi Hiep Nguyen, and Byong Taek Lee Fabrication and Chraterization of PLLA-PCL-BCP 3-D Scaffolds by Salt Leaching Method for Bone Tissue Engineering Applications KTERMS 143 Thi-Hiep Nguyen, Shin-Woo Kim, Young Ki Min, Yang Hun-Mo and Byong-Taek Lee In-vitro and In-vivo Studies of rhBMP2 coated PS/PCL-BMP2 Fibrous Scaffolds for Bone Regeneration KTERMS Rose Ann Franco, Thi Hiep Nguyen, Kap-Ho Lee, and Byong Taek Lee BCP incorporation in PCL/PLGA membranes for improved Tensile straing, invitro biocompatibility and invivo tissue regeneration KTERMS Andrew R Padalhin, Rose Ann Franco, Nguyen Thuy Ba Linh, Thi Hiep Nguyen, Shin-Woo Kim, Ju-Young Kim, Young-Ki Min, Hun-Mo Yang, and Byong Taek Lee Evaluation of the cytocompatibility and hemocompatibility properties of different PCL blends KTERMS Hyoung-suk Kim, Nguyen Thi Hiep, Young Ki Min, Ju-Young Kim, and Byong Taek Lee Fabrication of PVA-gelatin Hyrogel Loaded BCP Scaffold by Spongy Replica Method 14th Annual Meeting of Korean Tissue Engineering and Regenerative Rose Ann Franco, Nguyen Thi Hiep, BCP Loading on PCL/PLLA Membranes for Improved Mechanical Strength and Osteoblast Cytocompatibility, KMRS, Fall Conference, 2011 SADIASA Alexander, Nguyen Thi Hiep and Lee Byong Taek, Fabrication and Characterization PLLA-PCL-BCP 3-D Scaffolds by Salt Leaching Method for Bone Tissue Engineering Applications, Oral, KCS, Fall Conference, 2011 Trinh Quang Bao, Nguyen Thi Hiep and Lee Byong Teak In Vitro and In Vivo Study of Bone Defect Formation Using a Novel Scaffold Containing Solid Free-form PLGA Microspheres Fall Conference, Oral, KMRS, Jeju (Korea) , 2011 Nguyen Thi Kim Cuc, Nguyen Thi Hiep and Lee Byong Taek Fabrication of BCP loaded PCL/PLGA fibers as a scaffold for bone tissue engineering application Fall Conference, Poster, KMRS, Jeju (Korea) , 2011 10 Nguyen Thi Hiep, Shin-Woo Kim, Young-Ki Min, Hun-Mo Yang and Byong-Taek Lee Optimization of Corsslinked Polyvinyl Alcohol-Gelatin Hydrogels to Obtain High Mechanical Properties and Excellent Biocompatibility for Bone Regeneration Poster, KMRS, Jeju (Korea) , 2011 11 Rose Ann Franco, Nguyen Thi Hiep and Lee Byong Taek Fabrication and Characterization of Novel Electrospun PVPA/ PVA Nanofiber Matrix for Bone Tissue Engineering Fall Conference, Poster, KMRS, Jeju (Korea) , 2011 12 Trinh Quang Bao, Nguyen Thi Hiep, Sora-Son and Byong Taek Lee A new Drug Delivery System Using the Transcription of Biodegradable Poly(lactic-co-glycolic acid)/Biphasic Calcium Phosphates Injectable Bone Substitute KCS, poster, 2011 13 Trinh-Quang Bao, Nguyen-Thi Hiep, Nguyen-ThiKimCuc, Yang-KiMin, HunMoYang, and Byong-TaekLee Characterizations of Bone Mineral Formation on a New Ap/PF-PCL Fibrous Scaffold for Bone Tissue Engineering Biomaterials, poster, 2011 14 Thi-Hiep Nguyen and Byong-Taek Lee A Hybrid Electrospun PU/PCL Scaffold Satisfied the Requirements of Blood Vessel Prosthesis in terms of Mechanical Properties, Pore Size and Biocompatibility Biomaterials, poster, 2011 15 Nguyen Thi Hiep and Byong-Taek Lee Synthesis and Characterization of Crosslinked PVA-Gelatin Hydrogel using Genipin Cross-linker for spongy bone applications Fall Conference, Poster, KMRS, Muju (Korea), 2010 16 Lim Seo-Hyun, Nguyen Thi Hiep and Byong-Taek Lee Investigation of Small Artery Vessel from Blends PS/PCL Electrospun Fall Conference, KMRS, Muju (Korea), 2010 17 Nguyen Thi Hiep and Byong-Taek Lee Fabrication of PCL/PLGA-BCP Sponge for Cancellous Spongy Applications and Bone Marrow Differentiation Fall Conference, Oral, KCS, Jeju Island (Korea), 2010 144 18 Nguyen Thi Hiep and Byong-Taek Lee Implantation of Small Artery Vessel from Blends PCL/PU with and without Anti-thrombus Spring Conference, Oral, KMRS, 2010 19 Rose Ann Franco, Nguyen Thi Hiep and Byong-Taek Lee Preparation and Characterization of Chitosan Hydrogel on PCL/PLGA mat for Potential Skin Bioengineering Spring Conference, Poster, KMRS, 2010 20 Lim Seo-Hyun, Nguyen Thi Hiep, Hun-Mo Yang, Young-Ki Min, Ho-Yeon Song and Byong-Taek Lee Fabrication of Electro-spun PS/PCL for Hard Tissue and Its Biocompatibility Evaluation Spring Conference, Poster, KMRS, 2010 21 Thi-Hiep Nguyen and Byong-Taek Lee “Fabrication of a novel artificial Blood Vessel from electro-spun/hydrogel method: PCL/Gelatin-PVA and Their Biocompatibility Evaluation” Fall Conference, Poster, Biomaterials Society Conference Kist (Korea), 2009 22 Eun-yi Kim, Thi-Hiep Nguyen, Young-Ki Min, Ho-Yeon Song and Byong-Taek Lee Fabrication of Artificial Coronary Bypass Using Co-electro-spun of PU/PCL and Endothelial Cells Respond to Electro-spun Fibrous Mats Fall Conference, Poster, Biomaterials Society Conference Kist (Korea), 2009 23 Nguyen Thi Hiep, Young-Ki Min, Ho-Yeon Song and Byong-Taek Lee “Copolymer Electro-spun of Flexible and Non-flexible Polymer PLGA/PCL Blend for Tissue Engineering and It’s Biocompatibility” Fall Conference, Poster, KMRS, Pohang (Korea), 2009 24 Trinh-Quang Bao, Yang-Hee Kim, Nguyen-Thi Hiep, Young-Ki Min, Ho-Yeon Song and Byong-Taek Lee.” Fabrication simvastatin loaded porous PLGA microsphere as DDS for tissue regeneration” Spring Conference, Poster, KMRS, Muju (Korea), 2009 25 Nguyen Thuy Ba Linh, Thi-Hiep Nguyen, Hun Mo Yang, Young Ki Min and Byong-Taek Lee Cell Growing Behavior on the Electrospun PVA/GE nanofiber mats Spring Conference, Poster, KMRS, Muju (Korea), 2009 26 Nguyen Thi Phuong, Thi-Hiep Nguyen, Swapan Kumar Sarkar Ho-Yeon Song and Byong-Teak Lee “Fabrication PCL-BCP microfibrous hydrid composite mats by electrospinning and investigation of cell- material interaction by in vitro” KMRS, Muju (Korea), 2009 27 Thi-Hiep Nguyen, In-Seon Byun, Young-Ki Min, Hun-Mo Yang, Ho-Yeon Song and Byong-Taek Lee “Mechanical properties, Biodegradability and Biocompatibility of Coronary Bypass Artery with PCL Layer and PLGA/Chitosan Mats Using Electro-spinning” Spring Conference, Oral, KMRS, Muju (Korea), 2009 28 Thi Hiep Nguyen, In-Seon Byun, Ho-Yeon Song and Byong-Taek Lee “Fabrication of Fibrous Chitosan Mats Using Electro-spinning Process and Their Biocompatibility” Spring Conference, Poster, KMRS, Muju (Korea), 2009 29 Thi-Hiep Nguyen, Hun-Mo Yang, Ho-Yeon Song and Byong-Taek Lee “Evaluation of Mechanical properties of Bi-Layer Artificial Blood Vessel Made by PCL/Chitosan Composite by Electrospinning” Fall Conference, Poster, KMRS, Suwon (Korea), 2008 30 Thi-Hiep Nguyen, In-Seon Byun, Young-Ki Min, Ho-Yeon Song and Byong-Taek Lee “New Design of Coronary Bypass Artery with PCL Layer and PLGA/Chitosan Mat Using Electro-spinning” Fall Conference, Oral, KMRS, Suwon (Korea), 2008 31 Thi-Hiep Nguyen, Kim Young Hee, Rajat Kanti Paul, Ho-Yeon Song and ByongTaek Lee “Synthesis of Nano-Ag Incorporated PVA Fibrous Mats Using Electrospinning Method and Evaluation of Their Biocompatibility” Spring Conference, Poster, KMRS, Chongju (Korea), 2008 145 .. .Fabrication, In-vitro, In-vivo Evaluation of Hybrid Biopolymers for Artificial Soft and Hard Tissue Application Advisor: Professor Lee Byong-Taek Dissertation submitted for the degree of Doctor... Hematoxylin and Eosin staining of the defect of H, HBCP, H-RGD, HBMP2 and HBCP-BMP2 xvi 117 117 117 118 ABSTRACT Fabrication, In-vitro, In-vivo Evaluation of Hybrid Biopolymers for Artificial Soft and Hard. .. (b) and hybrid PU/PCL (c) membranes Fig Pressure strength of electro-spun PU, PCL and PU/PCL tubes Fig Cell viability of electrospun PU, PCL and hybrid PU/PCL membranes Fig Optical density of