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This is the first of two volumes that together provide an overview
of the latest advances in the generation and application of digital
twins in bioprocess design and optimization.Both processes have
undergone significant changes over the past few decades, moving
from data-driven approaches into the 21st-century digitalization of
the bioprocess industry. Moreover, the high demand for
biotechnological products calls for efficient methods during
research and development, as well as during tech transfer and
routine manufacturing. In this regard, one promising tool is the
use of digital twins, which offer a virtual representation of the
bioprocess. They reflect the mechanistics of the biological system
and the interactions between process parameters, key performance
indicators and product quality attributes in the form of a
mathematical process model. Furthermore, digital twins allow us to
use computer-aided methods to gain an improved process
understanding, to test and plan novel bioprocesses, and to
efficiently monitor them. This book explains the mathematical
structure of digital twins, their development and the model's
respective parts, as well as concepts for the knowledge-driven
generation and structural variability of digital twins. Covering
fundamentals as well as applications, the two volumes offer the
ideal introduction to the topic for researchers in academy and
industry alike.
This is the second of two volumes that together provide an overview
of the latest advances in the generation and application of digital
twins in bioprocess design and optimization. Both processes have
undergone significant changes over the past few decades, moving
from data-driven approaches into the 21st-century digitalization of
the bioprocess industry. Moreover, the high demand for
biotechnological products calls for efficient methods during
research and development, as well as during tech transfer and
routine manufacturing. In this regard, one promising tool is the
use of digital twins, which offer a virtual representation of the
bioprocess. They reflect the mechanistics of the biological system
and the interactions between process parameters, key performance
indicators and product quality attributes in the form of a
mathematical process model. Furthermore, digital twins allow us to
use computer-aided methods to gain an improved process
understanding, to test and plan novel bioprocesses, and to
efficiently monitor them. This book focuses on the application of
digital twins in various contexts, e.g. computer-aided experimental
design, seed train prediction, and lifeline analysis. Covering
fundamentals as well as applications, the two volumes offers the
ideal introduction to the topic for researchers in academy and
industry alike.
The second edition of this book constitutes a comprehensive manual
of new techniques for setting up mammalian cell lines for
production of biopharmaceuticals, and for optimizing critical
parameters for cell culture considering the whole cascade from lab
to final production. The chapters are written by world-renowned
experts and the volume's five parts reflect the processes required
for different stages of production. This book is a compendium of
techniques for scientists in both industrial and research
laboratories that use mammalian cells for biotechnology purposes.
Alternative Sources of Adult Stem Cells: Human Amniotic
Membrane, by S. Wolbank, M. van Griensven, R. Grillari-Voglauer,
and A. Peterbauer-Scherb;
*
Mesenchymal Stromal Cells Derived from Human Umbilical Cord
Tissues: Primitive Cells with Potential for Clinical and Tissue
Engineering Applications, by P. Moretti, T. Hatlapatka, D. Marten,
A. Lavrentieva, I. Majore, R. Hass and C. Kasper;
*
Isolation, Characterization, Differentiation, and Application of
Adipose-Derived Stem Cells, by J. W. Kuhbier, B. Weyand, C. Radtke,
P. M. Vogt, C. Kasper and K. Reimers;
*
Induced Pluripotent Stem Cells: Characteristics and Perspectives,
by T. Cantz and U. Martin;
*
Induced Pluripotent Stem Cell Technology in Regenerative Medicine
and Biology, by D. Pei, J. Xu, Q. Zhuang, H.-F. Tse and M. A.
Esteban;
*
Production Process for Stem Cell Based Therapeutic Implants:
Expansion of the Production Cell Line and Cultivation of
Encapsulated Cells, by C. Weber, S. Pohl, R. Poertner, P.
Pino-Grace, D. Freimark, C. Wallrapp, P. Geigle and P.
Czermak;
*
Cartilage Engineering from Mesenchymal Stem Cells, by C. Goepfert,
A. Slobodianski, A.F. Schilling, P. Adamietz and R. Poertner;
*
Outgrowth Endothelial Cells: Sources, Characteristics and Potential
Applications in Tissue Engineering and Regenerative Medicine, by S.
Fuchs, E. Dohle, M. Kolbe, C. J. Kirkpatrick;
*
Basic Science and Clinical Application of Stem Cells in Veterinary
Medicine, by I. Ribitsch, J. Burk, U. Delling, C. Geissler, C.
Gittel, H. Julke, W. Brehm;
*
Bone Marrow Stem Cells in ClinicalApplication: Harnessing Paracrine
Roles and Niche Mechanisms, by R. M. El Backly, R. Cancedda;
*
Clinical Application of Stem Cellsin the Cardiovascular System, C.
Stamm, K. Klose, Y.-H. Choi"
"Animal Cell Biotechnology: Methods and Protocols, Third
Edition" constitutes a comprehensive manual of state-of-the-art and
new techniques for setting up mammalian cell lines for production
of biopharmaceuticals, and for optimizing critical parameters for
cell culture from lab to final production. The volume is divided
into five parts that reflect the processes required for different
stages of production. In Part I, basic techniques for establishment
of production cell lines are addressed, especially high-throughput
synchronization, insect cell lines, transient gene and protein
expression, DNA Profiling and Characterisation. Part II addresses
tools for process and medium optimization as well as microcarrier
technology while Part III covers monitoring of cell growth,
viability and apoptosis, metabolic flux estimation, quenching
methods as well as NMR-based techniques. Part IV details
cultivation techniques, and Part V describes special applications,
including vaccine production, baculovirus protein expression,
chromatographic techniques for downstream as well as membrane
techniques for virus separation. Written in the successful "Methods
in Molecular Biology" series format, chapters include introductions
to their respective topics, lists of the necessary materials and
reagents, step-by-step, readily reproducible protocols, and notes
on troubleshooting and avoiding known pitfalls.
"Animal Cell Biotechnology: Methods and Protocols, Third
Edition" provides a compendium of techniques for scientists in
industrial and research laboratories that use mammalian cells for
biotechnology purposes.
The completion of the Human Genome Project and the rapid progress
in cell bi- ogy and biochemical engineering, are major forces
driving the steady increase of approved biotech products,
especially biopharmaceuticals, in the market. Today mammalian cell
products ("products from cells"), primarily monoclonals, cytokines,
recombinant glycoproteins, and, increasingly, vaccines, dominate
the biopharmaceutical industry. Moreover, a small number of
products consisting of in vitro cultivated cells ("cells as
product") for regenerative medicine have also been introduced in
the market. Their efficient production requires comprehensive
knowledge of biological as well as biochemical mammalian cell
culture fundamentals (e.g., cell characteristics and metabolism,
cell line establishment, culture medium optimization) and related
engineering principles (e.g., bioreactor design, process scale-up
and optimization). In addition, new developments focusing on cell
line development, animal-free c- ture media, disposables and the
implications of changing processes (multi-purpo- facilities) have
to be taken into account. While a number of excellent books
treating the basic methods and applications of mammalian cell
culture technology have been published, only little attention has
been afforded to their engineering aspects. The aim of this book is
to make a contribution to closing this gap; it particularly focuses
on the interactions between biological and biochemical and
engineering principles in processes derived from cell cultures. It
is not intended to give a c- prehensive overview of the literature.
This has been done extensively elsewhere.
The Cell-Surface Interaction, by J. S. Hayes, E. M. Czekanska and
R. G. Richards. Studying Cell-Surface Interactions In Vitro: A
Survey of Experimental Approaches and Techniques, by Stefanie
Michaelis, Rudolf Robelek and Joachim Wegener. Harnessing
Cell-Biomaterial Interactions for Osteochondral Tissue
Regeneration, by Kyobum Kim, Diana M. Yoon, Antonios G. Mikos and
F. Kurtis Kasper. Interaction of Cells with Decellularized
Biological Materials, by Mathias Wilhelmi, Bettina Giere and
Michael Harder. Evaluation of Biocompatibility Using In Vitro
Methods: Interpretation and Limitations, by Arie Bruinink and Reto
Luginbuehl. Artificial Scaffolds and Mesenchymal Stem Cells for
Hard Tissues, by Margit Schulze and Edda Tobiasch. Bioactive
Glass-Based Scaffolds for Bone Tissue Engineering, by Julia Will,
Lutz-Christian Gerhardt and Aldo R. Boccaccini. Microenvironment
Design for Stem Cell Fate Determination, by Tali Re'em and Smadar
Cohen. Stem Cell Differentiation Depending on Different Surfaces,
by Sonja Kress, Anne Neumann, Birgit Weyand and Cornelia Kasper.
Designing the Biocompatibility of Biohybrids, by Frank Witte,
Ivonne Bartsch and Elmar Willbold. Interaction of Cartilage and
Ceramic Matrix, by K. Wiegandt, C. Goepfert, R. Portner and R.
Janssen. Bioresorption and Degradation of Biomaterials, by Debarun
Das, Ziyang Zhang, Thomas Winkler, Meenakshi Mour, Christina I.
Gunter, Michael M. Morlock, Hans-Gunther Machens and Arndt F.
Schilling."
This is the first of two volumes that together provide an overview
of the latest advances in the generation and application of digital
twins in bioprocess design and optimization.Both processes have
undergone significant changes over the past few decades, moving
from data-driven approaches into the 21st-century digitalization of
the bioprocess industry. Moreover, the high demand for
biotechnological products calls for efficient methods during
research and development, as well as during tech transfer and
routine manufacturing. In this regard, one promising tool is the
use of digital twins, which offer a virtual representation of the
bioprocess. They reflect the mechanistics of the biological system
and the interactions between process parameters, key performance
indicators and product quality attributes in the form of a
mathematical process model. Furthermore, digital twins allow us to
use computer-aided methods to gain an improved process
understanding, to test and plan novel bioprocesses, and to
efficiently monitor them. This book explains the mathematical
structure of digital twins, their development and the model's
respective parts, as well as concepts for the knowledge-driven
generation and structural variability of digital twins. Covering
fundamentals as well as applications, the two volumes offer the
ideal introduction to the topic for researchers in academy and
industry alike.
This is the second of two volumes that together provide an overview
of the latest advances in the generation and application of digital
twins in bioprocess design and optimization. Both processes have
undergone significant changes over the past few decades, moving
from data-driven approaches into the 21st-century digitalization of
the bioprocess industry. Moreover, the high demand for
biotechnological products calls for efficient methods during
research and development, as well as during tech transfer and
routine manufacturing. In this regard, one promising tool is the
use of digital twins, which offer a virtual representation of the
bioprocess. They reflect the mechanistics of the biological system
and the interactions between process parameters, key performance
indicators and product quality attributes in the form of a
mathematical process model. Furthermore, digital twins allow us to
use computer-aided methods to gain an improved process
understanding, to test and plan novel bioprocesses, and to
efficiently monitor them. This book focuses on the application of
digital twins in various contexts, e.g. computer-aided experimental
design, seed train prediction, and lifeline analysis. Covering
fundamentals as well as applications, the two volumes offers the
ideal introduction to the topic for researchers in academy and
industry alike.
The editors of this special volume would first like to thank all
authors for their excellent contributions. We would also like to
thank Prof. Dr. Thomas Scheper, Dr. Marion Hertel and Ulrike
Kreusel for providing the opportunity to compose this volume and
Springer for organizational and technical support. Tissue
engineering represents one of the major emerging fields in modern
b- technology; it combines different subjects ranging from
biological and material sciences to engineering and clinical
disciplines. The aim of tissue engineering is the development of
therapeutic approaches to substitute diseased organs or tissues or
improve their function. Therefore, three dimensional biocompatible
materials are seeded with cells and cultivated in suitable systems
to generate functional tissues. Many different aspects play a role
in the formation of 3D tissue structures. In the first place the
source of the used cells is of the utmost importance. To prevent
tissue rejection or immune response, preferentially autologous
cells are now used. In particular, stem cells from different
sources are gaining exceptional importance as they can be
differentiated into different tissues by using special media and
supplements. In the field of biomaterials, numerous scaffold
materials already exist but new composites are also being developed
based on polymeric, natural or xenogenic sources. Moreover, a very
important issue in tissue en- neering is the formation of tissues
under well defined, controlled and reprod- ible conditions.
Therefore, a substantial number of new bioreactors have been
developed.
Animal Cell Biotechnology: Methods and Protocols, Third Edition
constitutes a comprehensive manual of state-of-the-art and new
techniques for setting up mammalian cell lines for production of
biopharmaceuticals, and for optimizing critical parameters for cell
culture from lab to final production. The volume is divided into
five parts that reflect the processes required for different stages
of production. In Part I, basic techniques for establishment of
production cell lines are addressed, especially high-throughput
synchronization, insect cell lines, transient gene and protein
expression, DNA Profiling and Characterisation. Part II addresses
tools for process and medium optimization as well as microcarrier
technology while Part III covers monitoring of cell growth,
viability and apoptosis, metabolic flux estimation, quenching
methods as well as NMR-based techniques. Part IV details
cultivation techniques, and Part V describes special applications,
including vaccine production, baculovirus protein expression,
chromatographic techniques for downstream as well as membrane
techniques for virus separation. Written in the successful Methods
in Molecular Biology series format, chapters include introductions
to their respective topics, lists of the necessary materials and
reagents, step-by-step, readily reproducible protocols, and notes
on troubleshooting and avoiding known pitfalls. Animal Cell
Biotechnology: Methods and Protocols, Third Edition provides a
compendium of techniques for scientists in industrial and research
laboratories that use mammalian cells for biotechnology purposes.
The second edition of this book constitutes a comprehensive manual
of new techniques for setting up mammalian cell lines for
production of biopharmaceuticals, and for optimizing critical
parameters for cell culture considering the whole cascade from lab
to final production. The chapters are written by world-renowned
experts and the volume's five parts reflect the processes required
for different stages of production. This book is a compendium of
techniques for scientists in both industrial and research
laboratories that use mammalian cells for biotechnology purposes.
The Cell-Surface Interaction, by J. S. Hayes, E. M. Czekanska and
R. G. Richards. Studying Cell-Surface Interactions In Vitro: A
Survey of Experimental Approaches and Techniques, by Stefanie
Michaelis, Rudolf Robelek and Joachim Wegener. Harnessing
Cell-Biomaterial Interactions for Osteochondral Tissue
Regeneration, by Kyobum Kim, Diana M. Yoon, Antonios G. Mikos and
F. Kurtis Kasper. Interaction of Cells with Decellularized
Biological Materials, by Mathias Wilhelmi, Bettina Giere and
Michael Harder. Evaluation of Biocompatibility Using In Vitro
Methods: Interpretation and Limitations, by Arie Bruinink and Reto
Luginbuehl. Artificial Scaffolds and Mesenchymal Stem Cells for
Hard Tissues, by Margit Schulze and Edda Tobiasch. Bioactive
Glass-Based Scaffolds for Bone Tissue Engineering, by Julia Will,
Lutz-Christian Gerhardt and Aldo R. Boccaccini. Microenvironment
Design for Stem Cell Fate Determination, by Tali Re em and Smadar
Cohen. Stem Cell Differentiation Depending on Different Surfaces,
by Sonja Kress, Anne Neumann, Birgit Weyand and Cornelia Kasper.
Designing the Biocompatibility of Biohybrids, by Frank Witte,
Ivonne Bartsch and Elmar Willbold. Interaction of Cartilage and
Ceramic Matrix, by K. Wiegandt, C. Goepfert, R. Portner and R.
Janssen. Bioresorption and Degradation of Biomaterials, by Debarun
Das, Ziyang Zhang, Thomas Winkler, Meenakshi Mour, Christina I.
Gunter, Michael M. Morlock, Hans-Gunther Machens and Arndt F.
Schilling."
Alternative Sources of Adult Stem Cells: Human Amniotic
Membrane, by S. Wolbank, M. van Griensven, R. Grillari-Voglauer,
and A. Peterbauer-Scherb;
*
Mesenchymal Stromal Cells Derived from Human Umbilical Cord
Tissues: Primitive Cells with Potential for Clinical and Tissue
Engineering Applications, by P. Moretti, T. Hatlapatka, D. Marten,
A. Lavrentieva, I. Majore, R. Hass and C. Kasper;
*
Isolation, Characterization, Differentiation, and Application of
Adipose-Derived Stem Cells, by J. W. Kuhbier, B. Weyand, C. Radtke,
P. M. Vogt, C. Kasper and K. Reimers;
*
Induced Pluripotent Stem Cells: Characteristics and Perspectives,
by T. Cantz and U. Martin;
*
Induced Pluripotent Stem Cell Technology in Regenerative Medicine
and Biology, by D. Pei, J. Xu, Q. Zhuang, H.-F. Tse and M. A.
Esteban;
*
Production Process for Stem Cell Based Therapeutic Implants:
Expansion of the Production Cell Line and Cultivation of
Encapsulated Cells, by C. Weber, S. Pohl, R. Poertner, P.
Pino-Grace, D. Freimark, C. Wallrapp, P. Geigle and P.
Czermak;
*
Cartilage Engineering from Mesenchymal Stem Cells, by C. Goepfert,
A. Slobodianski, A.F. Schilling, P. Adamietz and R. Poertner;
*
Outgrowth Endothelial Cells: Sources, Characteristics and Potential
Applications in Tissue Engineering and Regenerative Medicine, by S.
Fuchs, E. Dohle, M. Kolbe, C. J. Kirkpatrick;
*
Basic Science and Clinical Application of Stem Cells in Veterinary
Medicine, by I. Ribitsch, J. Burk, U. Delling, C. Geissler, C.
Gittel, H. Julke, W. Brehm;
*
Bone Marrow Stem Cells in ClinicalApplication: Harnessing Paracrine
Roles and Niche Mechanisms, by R. M. El Backly, R. Cancedda;
*
Clinical Application of Stem Cellsin the Cardiovascular System, C.
Stamm, K. Klose, Y.-H. Choi"
The editors of this special volume would first like to thank all
authors for their excellent contributions. We would also like to
thank Prof. Dr. Thomas Scheper, Dr. Marion Hertel and Ulrike
Kreusel for providing the opportunity to compose this volume and
Springer for organizational and technical support. Tissue
engineering represents one of the major emerging fields in modern
b- technology; it combines different subjects ranging from
biological and material sciences to engineering and clinical
disciplines. The aim of tissue engineering is the development of
therapeutic approaches to substitute diseased organs or tissues or
improve their function. Therefore, three dimensional biocompatible
materials are seeded with cells and cultivated in suitable systems
to generate functional tissues. Many different aspects play a role
in the formation of 3D tissue structures. In the first place the
source of the used cells is of the utmost importance. To prevent
tissue rejection or immune response, preferentially autologous
cells are now used. In particular, stem cells from different
sources are gaining exceptional importance as they can be
differentiated into different tissues by using special media and
supplements. In the field of biomaterials, numerous scaffold
materials already exist but new composites are also being developed
based on polymeric, natural or xenogenic sources. Moreover, a very
important issue in tissue en- neering is the formation of tissues
under well defined, controlled and reprod- ible conditions.
Therefore, a substantial number of new bioreactors have been
developed.
The completion of the Human Genome Project and the rapid progress
in cell bi- ogy and biochemical engineering, are major forces
driving the steady increase of approved biotech products,
especially biopharmaceuticals, in the market. Today mammalian cell
products ("products from cells"), primarily monoclonals, cytokines,
recombinant glycoproteins, and, increasingly, vaccines, dominate
the biopharmaceutical industry. Moreover, a small number of
products consisting of in vitro cultivated cells ("cells as
product") for regenerative medicine have also been introduced in
the market. Their efficient production requires comprehensive
knowledge of biological as well as biochemical mammalian cell
culture fundamentals (e.g., cell characteristics and metabolism,
cell line establishment, culture medium optimization) and related
engineering principles (e.g., bioreactor design, process scale-up
and optimization). In addition, new developments focusing on cell
line development, animal-free c- ture media, disposables and the
implications of changing processes (multi-purpo- facilities) have
to be taken into account. While a number of excellent books
treating the basic methods and applications of mammalian cell
culture technology have been published, only little attention has
been afforded to their engineering aspects. The aim of this book is
to make a contribution to closing this gap; it particularly focuses
on the interactions between biological and biochemical and
engineering principles in processes derived from cell cultures. It
is not intended to give a c- prehensive overview of the literature.
This has been done extensively elsewhere.
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