Contents
Cover
Half Title page
Title page
Copyright page
Preface
List of Contributors
Part I: Biomedical Materials
Chapter 1: Application of the Collagen as Biomaterials
1.1 Introduction
1.2 Structural Aspect of Native Tissue
1.3 Processing of Collagen Matrix
1.4 Conclusions and Future Perspectives
References
Chapter 2: Biological and Medical Significance of Nanodimensional and Nanocrystalline Calcium Orthophosphates
2.1 Introduction
2.2 General Information on “Nano”
2.3 Micron- and Submicron-Sized Calcium Orthophosphates versus the Nanodimensional Ones
2.4 Nanodimensional and Nanocrystalline Calcium Orthophosphates in Calcified Tissues of Mammals
2.5 The Structure of the Nanodimensional and Nanocrystalline Apatites
2.6 Synthesis of the Nanodimensional and Nanocrystalline Calcium Orthophosphates
2.7 Biomedical Applications of the Nanodimensional and Nanocrystalline Calcium Orthophosphates
2.8 Other Applications of the Nanodimensional and Nanocrystalline Calcium Orthophosphates
2.9 Summary and Perspectives
2.10 Conclusions
Closing Remarks
References and Notes
Chapter 3: Layer-by-Layer (LbL) Thin Film: From Conventional To Advanced Biomedical and Bioanalytical Applications
3.1 State-of-the-art LbL Technology
3.2 Principle of Biomaterials Based Lbl Architecture
3.3 LbL Thin Film for Biomaterials and Biomedical Implantations
3.4 LbL Thin Film for Biosensors and Bioassays
3.5 LbL Thin Film Architecture on Colloidal Materials
3.6 LbL Thin Film for Drug Encapsulation and Delivery
3.7 LbL Thin Film Based Micro/Nanoreactor
References
Chapter 4: Polycaprolactone based Nanobiomaterials
4.1 Introduction
4.2 Preparation of Polycaprolactone Nanocomposites
4.3 Characterization of Poly(caprolactone) Nanocomposites
4.4 Properties
4.5 Biocompatibility and Drug Delivery Application
4.6 Conclusion
Acknowledgement
References
Chapter 5: Bone Substitute Materials in Trauma and Orthopedic Surgery – Properties and Use in Clinic
5.1 Introduction
5.2 Types of Bone Grafts
5.3 Bone Substitute Materials
5.4 Combinations with Osteogenic and Osteoinductive Materials
5.5 Discussion and Conclusion
References
Chapter 6: Surface Functionalized Hydrogel Nanoparticles
6.1 Hydrogel Nanoparticles
6.2 Hydrogel Nanoparticles Based on Chitosan
6.3 Hydrogel Nanoparticles Based on Alginate
6.4 Hydrogel Nanoparticles Based on Poly(vinyl Alcohol)
6.5 Hydrogel Nanoparticles Based on Poly(ethylene Oxide) and Poly(ethyleneimine)
6.6 Hydrogel Nanoparticles Based on Poly(vinyl Pyrrolidone)
6.7 Hydrogel Nanoparticles Based on Poly-N-Isopropylacrylamide
6.8 Smart Hydrogel Nanoparticles
6.9 Self-assembled Hydrogel Nanoparticles
6.10 Surface Functionalization
6.11 Surface Functionalized Hydrogel Nanoparticles
References
Part II: Diagnostic Devices
Chapter 7: Utility and Potential Application of Nanomaterials in Medicine
7.1 Introduction
7.2 Nanoparticle Coatings
7.3 Cyclic Peptides
7.4 Dendrimers
7.5 Fullerenes/Carbon Nanotubes/Graphene
7.6 Functional Drug Carriers
7.7 MRI Scanning Nanoparticles
7.8 Nanoemulsions
7.9 Nanofibers
7.10 Nanoshells
7.11 Quantum Dots
7.12 Nanoimaging
7.13 Inorganic Nanoparticles
7.14 Conclusion
Acknowledgement
References
Chapter 8: Gold Nanoparticle-based Electrochemical Biosensors for Medical Applications
8.1 Introduction
8.2 Electrochemical Biosensors
8.3 Conclusion
References
Chapter 9: Impedimetric DNA Sensing Employing Nanomaterials
9.1 Introduction
9.2 Electrochemical Impedance Spectroscopy for Genosensing
9.3 Nanostractured Carbon Used in Impedimetric Genosensors
9.4 Nanostractured Gold Used in Impedimetric Genosensors
9.5 Quantum Dots for Impedimetric Genosensing
9.6 Impedimetric Genosensors for Point-of-Care Diagnosis
9.7 Conclusions (Past, Present and Future Perspectives)
Acknowledgements
References
Chapter 10: Bionanocomposite Matrices in Electrochemical Biosensors
10.1 Introduction
10.2 Fabrication of SiO2-CHIT/CNTs Bionanocomposites
10.3 Preparation of Bioelectrodes
10.4 Characterizations
10.5 Electrocatalytic Properties
10.6 Photometric Response
10.7 Conclusions
Acknowledgements
References
Chapter 11: Biosilica – Nanocomposites - Nanobiomaterials for Biomedical Engineering and Sensing Applications
11.1 Introduction
11.2 Silica Polymerization Process
11.3 Biocatalytic Formation of Silica
11.4 Biosilica Nanotechnology
11.5 Applications
11.6 Conclusions
References
Chapter 12: Molecularly Imprinted Nanomaterial-based Highly Sensitive and Selective Medical Devices
12.1 Introduction
12.2 Molecular Imprinted Polymer Technology
12.3 Molecularly Imprinted Nanomaterials
12.4 Molecularly Imprinted Nanomaterial-based Sensing Devices
12.5 Conclusion
References
Part III: Drug Delivery and Therapeutics
Chapter 13: Ground-Breaking Changes in Mimetic and Novel Nanostructured Composites for Intelligent-, Adaptive- and In vivo-responsive Drug Delivery Therapies
13.1 Introduction
13.2 Obstacles to the Clinician
13.3 Hurdles for the Pharmaceuticist
13.4 Nanostructures
13.5 Surface Coating
13.6 Cell Promoting, Toxicity and Clearance
13.7 Formulation Conditions and Parameters
13.8 Delivery Systems
13.9 Evaluation
13.10 Conclusions
References
Chapter 14: Progress of Nanobiomaterials for Theranostic Systems
14.1 Introduction
14.2 Design Concerns for Theranostic Nanosystems
14.3 Designing a Smart and Functional Theranostic System
14.4 Materials for Theranostic System
14.5 Theranostic Systems and Applications
14.6 Future Outlook
References
Chapter 15: Intelligent Drug Delivery Systems for Cancer Therapy
15.1 Introduction
15.2 Peptides for Nucleic Acid and Drug Delivery in Cancer Therapy
15.3 Lipid Carriers
15.4 Polymeric Carriers
15.5 Bactria-Mediated Cancer Therapy
15.6 Conclusion
References
Part IV: Tissue Engineering and Organ Regeneration
Chapter 16: The Evolution of Abdominal Wall Reconstruction and the Role of Nanobiotechnology in the Development of Intelligent Abdominal Wall Mesh
16.1 The Complex Structure of the Abdominal Wall
16.2 Need for Abdominal Wall Reconstruction
16.3 Failure of Primary Repair
16.4 Limitations of the Synthetic Meshes
16.5 Introduction of Biomaterials To Overcome Synthetic Mesh Limitations
16.6 Ideal Material for Abdominal Wall Reconstruction
16.7 Role of Bionanotechnology in Providing the Ideal Material
16.8 Future Directions
References
Chapter 17: Poly(Polyol Sebacate)-based Elastomeric Nanobiomaterials for Soft Tissue Engineering
17.1 Introduction
17.2 Poly(polyol sebacate) Elastomers
17.3 Elastomeric Nanocomposites
17.4 Summary
References
Chapter 18: Electrospun Nanomatrix for Tissue Regeneration
18.1 Introduction
18.2 Electrospun Nanomatrix
18.3 Polymeric Nanomatrices for Tissue Engineering
18.4 Biocompatibility of the Nanomatrix
18.5 Electrospun Nanomatrices for Tissue Engineering
18.6 Status and Prognosis
References
Chapter 19: Conducting Polymer Composites for Tissue Engineering Scaffolds
19.1 Introduction
19.2 Conducting Polymers
19.3 Synthesis of Conducting Polymers
19.4 Application of Conducting Polymer in Tissue Engineering
19.5 Polypyrrole
19.6 Poly(3,4-ethylene dioxythiophene)
19.7 Polyaniline
19.8 Carbon Nanotube
19.9 Future Prospects and Conclusions
Acknowledgements
References
Chapter 20: Cell Patterning Technologies for Tissue Engineering
20.1 Introduction
20.2 Patterned Co-culture Techniques
20.3 Applications of Co-cultures in Tissue Engineering
20.4 Concluding Remarks
Acknowledgements
References
Index
Biomedical Materials and Diagnostic Devices
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Illustration on front cover depicts interaction of stem cells into the nanobiomaterials for tissue engineering.
Cover design by Russell Richardson with illustration by Murugan Ramalingam and used with his permission
Library of Congress Cataloging-in-Publication Data:
Tiwari, Ashutosh, 1945-
Biomedical materials and diagnostic devices / edited by Ashutosh Tiwari… [et al.]
p. cm.
Includes bibliographical references and index.
ISBN 978-1-118-03014-1 (hardback)
[DNLM: 1. Biocompatible Materials. 2. Drug Delivery Systems. 3. Nanotechnology.
4. Tissue Engineering. QT 37]
610.28′4-dc23
2012025753
ISBN 978-1-118-03014-1
Preface
Engineering of advanced biomaterials has resulted in striking solutions to multifarious biomedical and diagnostic conudrums, including cell separation, stem-cell scaffolds, targeted drug delivery, treatments for hyperthermia, automated DNA extraction, gene targeting, resonance imaging, biosensors, tissue engineering and organ regeneration. The biomedical materials with the most promising potential combine biocompatibility with the ability to precisely adjust biological phenomenon in a controlled manner. The world market for biomedicals and diagnostic devices is expanding rapidly and is currently valued over US$1000 trillion. Likewise, academic research has kept pace with the market demand with over 50, 000 papers being published in the field last year. While the field of diagnostic devices has achieved considerable success, commercial returns in this sector are dominated by glucose sensing, despite the myriad of other possibilities for novel and useful analytical devices. Key areas such as drug delivery and regenerative medicine, not only represent huge opportunities to improve longevity and quality of life, but will also benefit from the fusion of ideas occurring within the emerging modern field of biomaterials. Molecular design for one application is finding utility across the field in a synergistic combination of solutions that brings together sensing, imaging, therapy and reconstruction in a plethora of exciting medical applications.
This book aims to provide an up-to-date overview of the fascinating field of biomedical materials and devices. This large volume includes twenty chapters divided into four main areas: biomedical materials, diagnostic devices, drug delivery and therapeutics, and tissue engineering and organ regeneration. It covers the latest research and developments in biomedical materials and medical devices: fabrication, performance and uses.
The chapters seek to address progress in successful design strategies for biomedical materials and devices such as the use of collagen, crystalline calcium orthophosphates, amphiphilic polymers, polycaprolactone, biomimetic assembly, bio-nanocomposite matrices, bio- silica, theranostic nanobiomaterials, intelligent drug delivery systems, elastomeric nanobiomaterials, electrospun nano-matrices, metal nanoparticles and a variety of biosensors. This book is intended to be suitable for a wide readership including university students and researchers from diverse backgrounds such as chemistry, materials science, physics, pharmacy, biological science and bio-medical engineering. It can be used not only as a text book for both undergraduate and graduate students, but also as a review and reference book for researchers in the materials science, bioengineering, pharmacy, biotechnology and nanotechnology.
Editors
Ashutosh Tiwari, PhD
Murugan Ramalingam, PhD
Hisatoshi Kobayashi, PhD
Anthony P.F. Turner, PhD, DSc
List of Contributors
Ülkü Anik graduated from Ege University (Izmir, Turkey) in chemistry (BSc) in 1995, in analytical chemistry (MSc) in 1998, in analytical chemistry (PhD) in 2003. She is an associate professor of analytical chemistry in Mu
la Sitki Koçman University (Mula, Turkey). She has published 30 articles mainly on nanstructure modified electrochemical biosensors.
Hajar Ashrafi PhD student of pharmaceutics, Shiraz University of Medical Sciences, Shiraz, Iran. Research interests include hydrogel nanoparticles in drug delivery; bioconjugation; surface-modified nanoparticles. Published 5 articles, 1 book, 1 book chapter and 15 research abstracts.
Amir Azadi PhD student of pharmaceutics, Tehran University of Medical Sciences, Iran. Research interests include hydrogel nanoparticles in drug delivery; surface-modified nanoparticles; pharmacokinetic evaluation of drug delivery systems. Published 15 articles, 1 book chapter and 30 research abstracts.
Alessandra Bonanni received her PhD in chemistry from Universitat Autonoma de Barcelona, Spain in 2008. After a post-doctoral experience at the National Institute for Materials Science (NIMS, Japan) she joined Nanyang Technological University in Singapore as senior researcher. Her current research is focused on the characterization and use of nanomaterials for the development of disposable electrochemical devices for next generation diagnostics.
Cherif Boutros obtained the Diploma of General Surgery and Master degree of Surgical Science from Paris University, France. He completed internship and residency in general surgery at New York Presbyterian Hospital in New York and Monmouth Medical Center in New Jersey. He also completed a Surgical Oncology fellowship at Roger Williams Medical Center in Providence, Rhode Island. Dr Boutros published and presented more than thirty papers in surgical oncology as well as in abdominal wall reconstruction in cancer patients. Dr Boutros is assistant professor of surgery at the University of Maryland School of Medicine and the Chief of Surgical Oncology at Baltimore Washington Medical Center.
Raluca Buiculescu obtained her MSc in biotechnology in 2006 from the “Politehnica” University of Bucharest. She completed her PhD in 2011 in the Laboratory of Analytical Chemistry of Prof. Chaniotakis. During these years she earned important experience in the synthesis and characterization of gold nanoparticles, semiconductor quantum dots and carbon nanomaterials and their conjugation with biomolecules with the purpose of constructing new biosensors systems. Her work gave rise to a significant number of refereed journal publications and poster or oral conference presentations. She currently works as a post doc scientist in the Laboratory of Analytical Chemistry of the University of Crete.
Nikos Chaniotakis is professor of analytical chemistry at the University of Crete, Greece. He studied at the University of Michigan (thesis with Prof. M. Meyerhoff) and then did his post-doctoral studies at Laboratorium für Organishe Chemie, Eidgenossische Technische Hochschule (ETH) Zentrum, Zurich, Switzerland under the supervision of Prof. W. Simon. He then started working at the University of Crete where he established the Laboratory of Analytical Chemistry. His research interest are focused in the area of the design of chemical sensors and biosensors, with emphasis in the utilization of opto-electrochemical nanomaterials, and nanostructures.
Pu Chen is a professor of chemical engineering and physics at the University of Waterloo, Canada. As Canada Research Chair in Nano-Biomaterials, Dr. Chen will continue to develop new engineering principles for molecular building block design and its applications in drug and gene delivery. He and his colleagues will strive for advancing the emerging fields in nanomedicine and bio-nanotechnology.
Qizhi Chen received her PhD degree in biomaterials from Imperial College London. She is currently an academic in the Department of Materials Engineering at Monash University, Australia. Previously she was employed by the National Heart and Lung Institute in London and the University of Cambridge. She has published more than 100 peer-reviewed journal articles and book chapters. Her research interests broadly cover polymeric, ceramic, metallic and composite materials for applications in biomedical engineering.
Jeong-Woo Choi received his PhD from the Department of Chemical & Biochemical Engineering, Rutgers University, USA (1990), DEng from the Department of Biomolecular Engineering, Tokyo Institute of Technology, Japan (2003), and MBA from the University of Durham, UK (2007). He is professor in the Department of Chemical and Biomolecular Engineering, and Director of Interdisciplinary Program of Integrated Biotechnology of Sogang University in Korea. He has done research in the fields of nanobioelectronics, especially bio-memory, protein chip, and cell chip. He has published more than 300 journal papers in the bioelectronics and biotechnology field.
Sergey V. Dorozhkin received his MS in chemical engineering in 1984 and PhD in chemistry in 1992. From 1996 to 2004, he held post-doctoral positions on calcium orthophosphates at five universities of four countries (France, Portugal, Germany, and Canada). Dr. Dorozhkin has authored more than 60 research papers, about 15 reviews, more than 10 book chapters, and 2 monographs.
Dipendra Gyawali is a faculty research associate at the University of Texas at Arlington. He obtained his BSc and MSc degrees (2009) in biomedical engineering from the University of Texas at Arlington. He has authored more than 10 publications, 2 book chapters, 10 abstracts, and 2 pending patents.
Mehrdad Hamidi professor of pharmaceutics and Dean School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran. His research interests are hydrogel nanoparticles in drug delivery; surface-modified nanoparticles; pharmacokinetic evaluation of drug delivery systems. He has published more than 50 articles, 1 book, 3 book chapters and 130 research abstracts.
Nader Hanna received his medical degree from Ain Shams University in Cairo, Egypt and completed his surgical residency at Tufts University. He also completed two fellowships at the University of Chicago. Dr. Hanna was featured in multiple news reports and was selected as one of “America’s Top Doctors for Cancer” in 2009. He was named on the “Top Doctors” List and was included in the “Guide to America’s Top Oncologists” by the Consumers’ Research Council of America. Dr Hanna has more than 50 publications in surgical oncology practice and research. Dr. Hanna is a professor of surgery at the University of Maryland and Director of Clinical Operations at the division of General and Oncologic Surgery.
Brian Ingalls is an associate professor in the Department of Applied Mathematics at the University of Waterloo, Canada. His research program is focused on applying tools from systems and control theory to study the regulation of intracellular networks.
Mousa Jafari is a PhD candidate in the Department of Chemical Engineering at the University of Waterloo, Canada. He is currently working on design and potential application of peptides for gene and drug delivery and tissue engineering purposes. He has published 2 book chapters, and 8 papers in peer-reviewed journals and documented 2 US patents.
D.N. Karunaratne obtained her PhD from the University of British Columbia, Vancouver, Canada. Currently she is a professor of chemistry at the University of Peradeniya, Sri Lanka. Her research interests are in the applications of carbohydrate liquid crystals in emulsion stabilization, and drug delivery through nanoencapsulation with polymers and liposomes. Dr. Karunaratne has authored 7 book chapters, 22 research articles in peer reviewed journals and obtained 6 US patents and 3 provisional US patent applications.
Akio Kishida obtained his PhD from Kyoto University in Polymer Chemistry. He is currently a professor in the Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University where his main research interests are polymer chemistry, surface chemistry, and regenerative medicine. He has published 158 peer-reviewed articles, 35 book chapters, and 24 review articles.
Hisatoshi Kobayashi is a group leader of WPI Research center MANA, National Institute for Material Science, Tsukuba Japan. Currently, he is President of International Association of Advanced Materials(IAAM). He has published more than 150 publications, books, and patents in the field of biomaterial science and technology. His current research interest is cell-nanomaterials interaction and the design and development of highly functionalized biodegradable scaffold for tissue engineering and nano-composites for medical devices.
Martin Wing Cheung Mak received his PhD in bioengineering in 2004 from The Hong Kong University of Science and Technology (HKUST). Currently, he is a senior research fellow jointly in the “Biosensors and Bioelectronics Centre” of the Department of Physics, Chemistry and Biology (IFM) and the “Integrative Regenerative Medicine (IGEN) Center” of the Faculty of Health Sciences at the Linköping University in Sweden. He has authored more than 30 articles, patents and conference proceedings in the field of colloidal materials and interfaces. Dr. Mak has developed various unique scientific skills and has pioneered new technologies to create functional colloidal materials as microencapsulated analytical system, advanced signal amplified biolabel system and transdermal drug carriers.
Pralay Maiti is professor and coordinator of the School of Materials Science and Technology, Institute of Technology at Banaras Hindu University. Pralay earned his PhD from the Indian Association for the Cultivation of Science, Kolkata. After spending 7 years at Cornell University, Toyota Technological Institute and Hiroshima University, he joined Central Leather Research Institute, Chennai and then moved to Banaras Hindu University in 2004 as a associate professor. His research expertise is in designing polymers for self-assembled thermoplastics, controlled biodegradation, polymer gels, radiation resistant electro active polymers, and application of polymeric materials for biomedical arena. His laboratory has synthesised novel nanoparticle induced piezoelectric polymeric materials, radiation resistant polymer, nanochannel conducting membrane, media for sustained drug release, and polymeric biocompatible materials for tissue engineering. He has published 65 papers mostly in high impact journals. He is the recipient of Prof. M. Santappa Silver Jubilee award by the Society of Polymer Science, India.
Debasish Mondal is a visiting post-doctoral researcher at the Department of Clinical and Experimental Medicine, Linkoping University, Sweden. He completed his PhD from School of Materials Science and Engineering at Nanyang Technological University (NTU), Singapore in 2010. He worked as a research associate and research fellow at NTU. His areas of research interest are bioengineering, nanobiomaterials, gene delivery, cell & tissue engineering, drug delivery and controlled release. Debasish has published more than 10 articles and conference proceedings.
Kwangwoo Nam earned a PhD in metallurgy from the University of Tokyo. He is currently an assistant professor at the Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University. His main research interests are in polymer physics, surface chemistry, and regenerative medicine. He has published more than 30 peer-reviewed articles and 9 book chapters.
Michael Palmer is a graduate student at the University of Texas at Arlington. He received his BSc degree from the University of California at San Diego.
Avinash Chandra Pandey holds four masters degrees namely MSc (Physics, 1984), MBA (Marketing, 1993) and MSc (Mathematics, 1996) from the University of Allahabad, India and MTech (Computer Science) from the Motilal Nehru National Institute of Technology, Allahabad, India as well as a DPhil from the University of Allahabad in 1995. Dr. Pandey is working as professor in atmospheric and oceanic sciences, University of Allahabad, India. He has more than 150 scientific papers in international and national conferences and Journals to his credit.
Bhim Bali Prasad is currently a professor at Banaras Hindu University, India where he has mentored 20 PhD students and published 90 research papers. He received his BSc degree in 1972, MSc degree in 1974, and PhD degree in 1978 from Banaras Hindu University, India. He is a recipient of several national awards including IAAM medal-2011. At present, he is leading a research group working in the field of MIP.
Murugan Ramalingam is an associate professor of biomaterials and tissue engineering at the Institut National de la Santé et de la Recherche Médicale, Faculté de Chirurgie Dentaire, Université de Strasbourg (UdS), France. Concurrently he holds an adjunct associate professorship at Tohoku University (Japan). He received his PhD (biomaterials) from the University of Madras. His research interests are focused on the development of multiphase biomaterials, through conventional to nanotechnology to biomimetic approaches, cell patterning, stem cell differentiation and tissue engineering. He has authored more than 125 publications and is Editor-in-Chief of Journal of Bionanoscience and Journal of Biomaterials and Tissue Engineering.
Dipak Sarker gained a PhD in physics in 1995. He has worked at universities and research institutes in the UK, France and Germany and now working in the School of Pharmacy at the University of Brighton (UK). His research involves medical nanotechnology. He has published a specialist book, two book chapters and more than 60 scientific papers.
Azadeh Seidi is a biochemist at Okinawa Institute of Science and Technology, Japan. Since earning her PhD from Tokyo Institute of Technology in 2007, she has focused her activities on biomedical researches on biochemical and engineering.
Yashpal Sharma graduated in chemistry from the G. J. University of Science and Technology, Hisar, India in 2012. He has been awarded a NIMS internship fellowship, Japan to carry out research in bio-functional materials group at the National Institute for Materials Science, Japan under the supervision of Dr. Hisatoshi Kobayashi and Dr. Ashutosh Tiwari on temperature responsive biomaterials for tissue regeneration. He is the recipient of the Young Scientist Award from the International Association of Advanced Materials (IAAM) in 2011. His research interests include smart micro and nano materials for supercapacitors, fuel cells, batteries and biological applications.
Narendra Kumar Singh earned his MSc degree (2005) in chemistry from Purvanchal University, India. In 2007 he joined the School of Materials Science and Technology, BHU, Varanasi as a junior research fellow in DBT sponsored project for his PhD Degree in material science and technology. He became a senior research fellow in 2009. He has visited the University of Guelph, Canada as visiting researcher through the Canadian Commonwealth scholarship programme. He was awarded the Senior Research Fellow Award in 2011 from the Council of Scientific & Industrial Research (CSIR), Human Resource Development Group, India. He has published five research papers in peer-reviewed journals and one book chapter. His current research interest includes the fabrication of biodegradable polymer nanobiohybrid scaffolds for targeted drug delivery and biomedical applications.
Ravindra P. Singh, earned his MSc and PhD in biochemistry from Lucknow University, India. Currently, he is working as a scientist at the Nanotechnology Application Centre, Allahabad University. He has been credited with several national and international awards and is the author of more than 30 research articles and 12 book chapters.
Hany Sobhi obtained his PhD in clinical bioanalytical chemistry at Cleveland State University, USA in 2008. He was appointed as an assistant professor of organic and clinical chemistry at Coppin State University Baltimore in 2010. Dr. Sobhi is an active researcher in translational research, and development of strategies for synthesis bioorganic molecules for clinical diagnosis and understands the pathogenetic mechanisms underlying the clinical manifestations of mitochondrial and cancer diseases. He has published sixteen research articles, and in 2011 he was awarded Faculty Scholar in Cancer Research from The American Society for Cancer Research AACR.
Madjid Soltani is a PhD student in the Waterloo Institute for Nanotechnology and Chemical Engineering Department, University of Waterloo, Canada. He studied mechanical engineering with the focus on numerical and computational modeling of transport phenomena for his undergraduate and Master degrees. He is currently working on a mathematical model of interstitial fluid behavior in physiological systems containing a solid tumor. He has published more than 20 journal and conference papers.
Ashutosh Tiwari is an assistant professor at the Biosensors and Bioelectronics Centre, IFM-Linkoping University; Editor-in-Chief of Advanced Materials Letters; a materials chemist and graduate from University of Allahabad, India. Dr. Tiwari is also honoured as a visiting professor in many prestigious institutions worldwide. Just after he completed his doctorate degree, he joined as a young scientist at National Physical Laboratory, India and later moved to University of Wisconsin, USA for postdoctoral research. He is actively engaged as reviewer, editor and member of scientific bodies around the world. Dr. Tiwari obtained various prestigious fellowships including JSPS, Japan; SI, Sweden; and Marie Curie, England/Sweden. In his academic carrier, he has published more than 175 articles, patents and conference proceedings in the field of materials science and technology. He has also edited/authored ten books on the advanced state-of-the-art of materials science with many publishers. Dr. Tiwari has been honoured by the prestigious ‘The Nano Award’ and ‘Innovation in Materials Science Award and Medal’ in 2011.
Atul Tiwari is an associate research faculty at the Department of Mechanical Engineering in the University of Hawaii, USA. He received his Master degree in organic chemistry and PhD in polymer science from universities in India. He earned the Chartered Chemist and Chartered Scientist status from the Royal Society of Chemistry, UK. His areas of research interest include the development of silicones and graphene materials for various industrial applications. Dr. Tiwari has invented several international patents pending technologies that have been transferred to industries. He has been actively engaged in various fields of polymer science, engineering, and technology and has published more than 50 scientific peer-reviewed journal papers, book chapters and books related to material science.
Mahavir Prasad Tiwari has worked for his PhD degree under the supervision of Professor Bhim Bali Prasad at Banaras Hindu University, India. He received his BSc in 2005 and MSc in 2007 from Purvanchal University. His research interests lie in the field of solid phase extraction/microextraction, molecularly imprinted polymers, and electroanalytical chemistry.
Richard T. Tran is a post-doctoral research fellow at the University of Texas at Arlington. He obtained a BSI in bioinformatics at Baylor University and a PhD in bioengineering at the University of Texas at Arlington. He has authored more than 10 publications, 3 book chapters, 25 abstracts, and has 3 pending patents.
Manel del Valle received his PhD in analytical chemistry (1992) from the Universitat Autonoma de Barcelona, Spain. He is currently a professor of analytical chemistry at UAB, member of the Sensors and Biosensors group, and head of chemistry studies. He has authored more than 160 research papers in the field of electrochemical sensors. He is the leader of research lines of sensor arrays and electronic tongues, as well as the use of Electrochemical Impedance Spectroscopy for biosensing.
E. M.M. Van Lieshout graduated in medical biology at the University of Nijmegen, the Netherlands and obtained a PhD in 1998. She is head of research at the Trauma Research Unit of Erasmus MC in Rotterdam, the Netherlands. Her research interests include bone healing biology and efficacy of interventions in trauma care. Dr. Van Lieshout (co)authored more than 100 peer-reviewed articles and two book chapters.
Jian Yang is an associate professor of bioengineering at the University of Texas at Arlington. He was the recipient of NSF CAREER award in 2010 and outstanding young faculty award at UTA College of Engineering in 2011. Dr. Yang has authored more than 50 journal articles, 15 issued/pending patents, and 4 book chapters.
Bahram Zargar is a PhD candidate in the Department of Chemical Engineering at the University of Waterloo, Canada. His Bachelor and Masters degrees were in Mechanical Engineering. His research programme is focused on synthetic biology and bacteria mediated cancer therapy.
Collagen is the protein of connective tissue in mammals. The content of collagen in the total protein is approximately 30% of the mammalian tissues. Due to its good cytocompatibility, researchers use this material for the biomedical research application. However, the control of its physical and biological properties is difficult. There are two obstacles in collagen application: 1) difficulty in regeneration of the collagen properties, and 2) difficulties in controlling the properties of the collagen products. The collagen is easily denatured and affected by the environment, which leads to unexpected results. On the other hand, the crosslinker to suppress the denaturation may cause the stiffness of the collagen product. So the researchers are investigating new ways to prepare a collagen product which can be used as a biomaterial for biomedical research application. An important component of the research is the structure and the function of extracelluar matrix (ECM). That is, there is biorelevant structure-function-property relationship, which alters its function as an ECM. Recent studies on decellularized tissue is also based on the fact that the native structure of the ECM can be preserved, and therefore may perform the function of the original tissue. So, by replicating its microstrutcure and producing a collagen fiber complex, it is expected that the function of ECM can be replicated. In this chapter, we will be introducing recent studies on the preparation of a collagen matrix based on fibrillogenesis, orientation, complex formation and layered structure, and how these structures alter the physical and biological properties.
Keywords: Collagen, decellularization, extracellular matrix, fibrillogenesis, microenvironment, regenerative medicine
Collagen is an extracellular-matrix (ECM) protein that plays an important role in the formation of tissues and organs and is involved in various functional expressions of cells [1]. A native ECM is a complex fiber-composite material in which collagen fibrils are a major component [2]. The function of an ECM is to provide support, tensile strength, and scaffolding for the tissue and cells. In addition, it should serve as a three-dimensional structure for cell adhesion and movement and as a storage depot for growth factors, chemokines, and cytokines; and it should provide signals for morphogenesis and differentiation [3]. Approximately 30% of all vertebrate body protein is composed of collagen. Among these, the highest collagen composition can be found for the tendon, bone and cornea where 90% of ECM is collagen. Mainly, the collagen can be distinguished into two types; fibrillar and non-fibrillar. There are 28 types of collagen and the collagen types I, II and III are the classical fibril-forming collagens and account for 80–90% of all collagens in the human body. Collagen fibril is very important from the aspect that its properties and the morphology provide the key to the scaffolding structures in the body according to the location.
It has been shown that the collagen possesses non-immunogenicity and good cell compatibility, and can be obtained from various sources. These make collagen popular among biomaterials researchers, and diverse methods have been adopted for its application in the biomedical fields. The collagen is purified after being treated with pH adjustment or pepsin digestion. Either way, the collagen should be water soluble in order to process it for use as a collagen matrix for biomaterial applications. There are several kinds of collagen matrix; gel, film, micropartices, conjugats, minipellets or sponge [1, 4]. However, there are still many problems to overcome. For example, the collagen which is available in the marketplace is hydrophilic, which absorbs water at a high rate. So, the uncross-linked collagen matrix possesses low mechanical strength and fast degradation rate in aqueous solution. The collagen matrix degrades by the collagenase, so this makes the collagen applicable in some biomedical products where the biodegradation in the living body is required. However, control of the biodegradation is not easy. The properties of the collagen matrix can be controlled by cross-linking. The cross-linking is executed chemically or physically. Furthermore, using the same cross-linking process, the collagen matrix can be functionalized by immobilization or, blend of a second component. The collagen is composed of amino acid groups where the chemical reaction can be executed. Mainly, the cross-linking is executed using ε-amino groups of lysine or hydrolysine, and aspartic acid or glutamic acid residues. These residues are highly reactive and can be easily functionalized. The cross-linking can change physical and biological properties of the collagen matrix and can be applied for the loading of the drugs. For the chemical cross-link, glutaraldehyde, formaldehyde, hexamethyelenediisocynate, polyepoxy compounds, carbodiimides, and acyl azides are commonly used [1, 4–14]. These show a good result in vivo, such as suppressing the inflammatory response and promoting the healing response. However, there are still several problems to be overcome. Although the collagen gels, sponges or films that have been cross-linked show an increase in the mechanical strength, the cross-link which consumes the functional groups are consumed for the cross-linking site, which may affect the biological properties. Moreover, the stiffness of the ECM is also a very important parameter, but it is not easy to control the stiffness of the collagen gel by cross-linking or a change in the collagen solution. That is, a stiff collagen gel can be prepared, but a gel with viscoelasticity cannot be prepared. This is important because most of the native tissue possesses visocelasticity which contributes to the toughness [15, 16]. A number of collagen matrices were reported, but the collagen products available in the marketplace is still scarce because of the problems mentioned above, so a new approach was required to move to the next step.
Before designing a biomaterial, it is necessary to understand the environment of the living body. When the biomaterial is designed for application in tissue engineering and regenerative medicine, the objective is the repair and remodeling of the damaged ECM and tissue, ultimately regenerating its function. The function of the ECMs is deeply related to the behavior of the cells which is affected by the cell-materials interaction. That is, the control of the cells behavior is very important in the aspect of regenerating the function of the ECMs. The cell is immersed in a dynamic landscape composed of insoluble macromolecules of the ECM, soluble bioactive factors and neighboring cells [17]. The environment which controls the fate of the cell inside the living body is called cellular microenvironment. It is very important in the aspect that the ultimate tissue structure and its function are decided by factors contributing to the cellular microenvironment. For this, there needs to be a fundamental understanding on the cellular microenvironment for the materials design. The cellular microenvironment is the environment in the living body which controls the fate of the cells. The microenvironment is composed of signals from the neighboring cells, physical stimuli, soluble factors such as growth factors, and insoluble factors such as ECM. The ECM has been shown to influence cell mitogenesis and chemotaxis [18, 19], direct cell differentiation [20–23], and to induce constructive host tissue remodeling responses [24–26]. The cells from the ECM sense, integrate and proceed the signals to determine behavior and functions, and the information is passed bidirectionally as the microenvironment is remodeled by the cells.
Development of biomaterials for tissue engineering and regenerative medicine has been approached mainly from the aspect of controlling the soluble and insoluble factors. As for the insoluble factor, diverse materials – natural or synthetic – are being investigated. The main goal of using these materials is to replicate the function of the ECM temporarily or permanently. By loading soluble factors in the materials, researchers tried to control the fate of the cells or stimulate the regeneration of the damaged tissues. On the other hand, manipulation of the morphology, microphase, surface physical properties and chemical properties of the material is a major approach for the control of the insoluble factors. These methods show good results and some of them are actually used for clinical practice.
Since the ECM is mainly composed of collagen, use of collagen to replicate its function is actively executed. It should be noted that the function of the ECM is different according to the type of tissue such as cornea, brain, skin, tendon, or blood vessel, where they need to perform a certain function. So the design of the ECM using collagen should be different according to the targeted tissue. However, although the tissues perform different functions, the common aspect of the tissue is that all are made up of collagen fibrils. That is, in order to design a material which may replicate the function of ECMs, fibrillized structure should be considered. Furthermore, it should be acknowledged that the design should include a nanometer to centimeter scale. The schematic structural images of respective tissue from the nanometer to centimeter scale are shown in Figure 1.1. Yip discussed the importance of careful consideration of biorelevant structure-function-property relationships in the design of biomaterials [27]. That is, the regeneration of the physical properties of native ECM is important for the regeneration of biological properties. The importance of the structure can be seen in research related to the decellularized tissue which is discussed in the next section.
Figure 1.1 The scale from the nano-scale to the macro-scale. The collagen matricesdconsist of nano-scale no larger than the microfibril, but the actual scale of the ECM or the tissue is much larger.
The decellularized tissue is a native tissue in which the cells are eliminated by certain treatment. Decellularization of tissue is based on the fact that preservation of the native ultrastructure and composition of ECM is possible [26]. The methods for the decellularization include use of chemical agents (ionic detergents, non-ionic detergents, acids and bases, hypotonic and hypetonic solution, and solvents), biological agents (enzymes and chelating agents), and physical treatment (temperature, pressure and electroporation). It should be understood that every cell removal agent and method will alter ECM composition and cause some degree of ultrastructure disruption. For example, the use of some chemical agents such as sodium dodecyl sulfate (SDS) may cleave the collagen fibrils, but use of physical treatment such as high pressurization would not affect the main structure [26, 28–30]. Furthermore, incomplete rinsing of chemical agents or the cell debris after decellularization process may cause toxicity. However, the minimization of these undesirable effects, rather than complete avoidance by the living body, is the objective of decellularization. So, the focus is set on complete removal of the cells and preservation of the ultrastructure. The methods for the decellularization should be carefully considered according to the density of the fibers, the thickness and the lipid contents. Moreover, the complete washing of the cell debris or the chemical agents after decellularization should be executed because this could cause toxicity.
The mechanical strength after the elimination of the cells is maintained and the regeneration around the implanted decellualrized tissue occurs without serious inflammatory response. So, the decellularization can be executed for the partial or full organs. It should be noted that the native tissue possesses complex structure and the whole structure – either macro or micro – is maintained after the appropriate decellularization process. Furthermore, the degradation of the decellularized tissue is slow, and the remodeling of the damaged tissue occurs without any problems. The regeneration within the living body occurs on the implanted decellularized tissue and starts to function as a replacement. Furthermore, the high mechanical strength of the decellularized tissue would endure the physical stress inside the living body [29, 31–32]. So many decellularized tissue products such as dermis, heart valve, blood vessel, bone and so on, have been introduced to the markets and are enjoying success.
The key for the success of the biomaterials for regenerative medicine is control of the cells’ fate which depends on the materials characteristics; three-dimensional ultrastructure, surface topology and composition of the ECM [17]. The successful point for decellularized tissue is that the three-dimensional ultrastructure, surface topology and composition of the ECM is maintained after the process. So, in order to reproduce the physical and biological properties of the ECM, we should first mimic its three factors as written above. The key points are the fibril formation, orientation, complex formation with second component such as GAG or elastin, and multiple layers. Since the structure of ECM differs according to the tissue, the mimicking of the structure should also be different according to what kind of tissue the researchers want to make. This is because the key function is different according to the tissue. For example, the tendon should have fibrillar structure with high orientation, the cornea should have fibrillar lattice structure, blood vessels should possess elastin-complex fibril structure with multiple layers and high orientation of collagen fibers, and skin should have elastin-complex fibril structure disregarding the orientation. Such ECM structures allow the various tissues to possess certain physical and biological properties adequate for functional performance. So, the structural consideration for replicating the function of tissue is very important.