Tissue Engineering

by Palsson, Bernhard O.; Bhatia, Sangeeta N.

• ISBN13: 9780130416964
• ISBN10: 0130416967
• Edition: 1st
• Format: Hardcover
• Copyright: 2003-07-30
• Publisher: Prentice Hall

Summary

This book--the first in its field--lays the foundation for individuals studying tissue engineering. It provides a conceptual framework that includes exposure to all the necessary background material in all areas. KEY TOPICS A four-part presentation covers quantitative cell and tissue biology, cell and tissue characterization, engineering methods and design, and clinical implementation. For cell culture scientists and engineers.

Table of Contents

Preface	xvii
Introduction	1	(19)
Cells as Therapeutic Agents	2	(2)
Illustrative Examples	4	(7)
Cartilage and chondrocytes	5	(1)
Liver	5	(2)
Pancreas β-islet cells	7	(1)
Skin	8	(1)
Bone-marrow transplantation (BMT)	8	(3)
Tissue engineer faces diverse challenges	11	(1)
Cell Numbers and Growth Rates	11	(4)
Cell numbers in vivo: orders of magnitude	12	(1)
What are clinically meaningful numbers of cells?	12	(1)
What are the fundamental limitations to the production of primary cells?	12	(2)
How rapidly do primary cells grow in culture?	14	(1)
How are these cells currently produced?	15	(1)
How are these cells preserved and harvested?	15	(1)
How are cells best delivered?	15	(1)
Outline of Book	15	(2)
Summary	17	(1)
Further Reading	17	(3)
Part I Quantitative Cell and Tissue Biology
Tissue Organization	20	(14)
Tissue Components	20	(7)
Extracellular matrix	20	(5)
Cells	25	(2)
Tissue Types	27	(2)
Epithelial tissues	27	(1)
Connective tissue	28	(1)
Other tissue types	28	(1)
Functional Subunits	29	(1)
Problem Decomposition	30	(3)
Summary	33	(1)
Further Reading	33	(1)
Tissue Dynamics	34	(12)
Dynamic States of Tissues	35	(1)
Homeostasis in Highly Prolific Tissues	35	(3)
Bone marrow	35	(1)
Villi in the small intestine	36	(1)
Skin	37	(1)
Tissue Repair	38	(5)
Sequence of events that underlie wound healing	38	(2)
Engineering wound healing	40	(2)
Fetal wound healing	42	(1)
Tissue Dynamics as Interacting Cellular-Fate Processes	43	(1)
Summary	44	(1)
Further Reading	45	(1)
Morphogenesis	46	(15)
Morphogenic Processes	46	(4)
Induction	46	(2)
Important mesenchymal-epithelial interaction	48	(1)
Adult transdifferentiation	48	(1)
Gastrulation	48	(2)
Morphogenic Dynamics	50	(7)
Initiation of morphogenesis	51	(1)
Spatio-temporal process	51	(1)
Final state	52	(1)
Some cellular processes involved in morphogenesis	52	(5)
Constraints on Morphogenesis	57	(2)
Summary	59	(1)
Further Reading	60	(1)
Stem Cells	61	(13)
Basic Concepts	61	(4)
Stem-cell properties	61	(2)
Telomeres and self-renewal	63	(1)
Stem cells and tissue engineering	64	(1)
Examples of Stem-Cell Systems	65	(4)
Mesenchymal stem cells (MSC)	65	(1)
Liver stem cells	66	(1)
Neuronal stem cells	67	(1)
Embryonic stem cell: the mother of all cells	67	(2)
Dynamic Function of Stem-Cell Systems	69	(4)
Conceptual models of stem-cell proliferative behavior	69	(1)
Dynamic models of stem cell proliferative behavior	70	(3)
Summary	73	(1)
Further Reading	73	(1)
Cellular-Fate Processes	74	(31)
Cell Differentiation	74	(7)
Differentiation as measured by changes in gene expression	74	(2)
Differentiation as measured by changes in cell function	76	(3)
Describing cell differentiation mathematically	79	(2)
Cell Migration	81	(6)
Underlying biochemical process	81	(2)
Describing cell migration mathematically	83	(4)
Cell Division	87	(6)
Mitotic cell cycle	87	(2)
Describing the cell cycle mathematically	89	(4)
Cell Death	93	(3)
Biological description of apoptosis	93	(2)
Describing apoptosis mathematically	95	(1)
Dynamics of Interacting Cellular-Fate Processes	96	(7)
Effects of cell division on the differentiation process	96	(3)
Dynamic interplay among differentiation, division, and apoptosis	99	(4)
Summary	103	(1)
Further Reading	104	(1)
Coordination of Cellular-Fate Processes	105	(27)
Soluble Signals	105	(12)
Types of growth factors and chemokines	106	(1)
Sending a paracrine signal	106	(3)
Receiving a signal	109	(2)
Processing a signal	111	(1)
Integrated responses	112	(1)
Soluble growth-factor receptors	113	(3)
Malfunctions in soluble signaling	116	(1)
Cell--Extracellular Matrix Interactions	117	(7)
Binding to the ECM	118	(2)
Modifying the ECM	120	(1)
Analyzing the rate of ECM modification	120	(2)
Malfunctions in ECM signaling	122	(2)
Direct Cell--Cell Contact	124	(3)
Cell junctions in tissues	124	(2)
Malfunctions in direct cell-cell contact signaling	126	(1)
Response to Mechanical Stimuli	127	(1)
Interaction between Signaling Mechanisms	128	(2)
Multiple-input/single-output model in fibroblast growth-factor-2 signaling	128	(2)
Summary	130	(1)
Further Reading	130	(2)
Part II Cell and Tissue Characterization
High-Throughput Biological Data	132	(22)
Basics of Molecular Biology	133	(2)
DNA molecule	133	(1)
Some historical milestones	134	(1)
Genomics	135	(5)
Chain termination	135	(1)
Automated sequencing	136	(2)
Informatics challenge	138	(1)
Sequence variation and individuality	139	(1)
Sequence annotation	139	(1)
Transcriptomics	140	(6)
Measuring how genomes are used	140	(2)
Microarray data analysis	142	(3)
Using gene-expression profiling	145	(1)
Proteomics	146	(2)
Metabolomics	148	(2)
Phenomics	150	(1)
Era of Systems Biology	151	(1)
Summary	152	(1)
Further Reading	153	(1)
Cell and Tissue Properties	154	(18)
Basic Tools	154	(5)
Microscopy	154	(1)
Detection of biochemical components	155	(1)
In vivo imaging	156	(3)
Measurement of Cell Characteristics	159	(9)
Cell morphology	159	(1)
Cell number and viability	160	(2)
Cell-fate processes	162	(1)
Measuring cell motility	162	(2)
Cell function	164	(1)
Mechanical	165	(3)
Measurement of Tissue Characteristics	168	(2)
General appearance	168	(1)
Cellular component	168	(1)
Extracellular matrix component	168	(1)
Function	168	(1)
Mechanical measurements	169	(1)
Physical properties	170	(1)
Summary	170	(1)
Further Reading	171	(1)
Cell and Tissue Culture	172	(17)
Definition and History	172	(1)
Types of Tissue Culture	173	(3)
Types of primary culture	173	(1)
Cell lines	174	(1)
Immortalized cell lines	175	(1)
Variation in cell lines	176	(1)
Media	176	(5)
Dissolved gases	176	(3)
Advantages and disadvantages of serum	179	(2)
Culture Environment and Maintenance of Cells In Vitro	181	(3)
Tissue-culture environment	181	(2)
Kinetics of growth	183	(1)
Characterization of Cell Function in Tissue Culture	184	(1)
Cryopreservation	184	(3)
Contaminants	187	(1)
Summary	187	(1)
Further Reading	188	(1)
Gene Transfer	189	(19)
Gene Transfer for Gene Therapy	189	(2)
Gene-Transfer Methods	191	(7)
Retrovirally mediated gene transfer	191	(2)
Adenovirus-mediated gene transfer	193	(3)
Nonviral methods	196	(2)
Retrovirally Mediated Gene-Delivery Process	198	(6)
Finding the target cell	198	(3)
Nonspecific virus binding to the target cell	201	(2)
Specific virus binding to the target cell	203	(1)
Viral entry	203	(1)
Gene Transfer for Modifying Cellular Functions	204	(2)
Summary	206	(1)
Further Reading	206	(2)
Part III Engineering Methods and Design
Time Constants	208	(15)
Definition of Time Constants	208	(3)
General definitions	208	(1)
Linear systems	209	(2)
Important Time Constants	211	(6)
Diffusion	211	(3)
Chemical reactions	214	(1)
Fluid flow	215	(1)
Biological time constants	216	(1)
Simplifying Dynamic Descriptions	217	(4)
Basic concept	217	(1)
Simultaneous diffusion and chemical reaction	218	(3)
Summary	221	(1)
Further Reading	222	(1)
Scaling up for Ex Vivo Cultivation	223	(21)
Using in vivo Conditions as a Guide	223	(3)
Respiratory functions of blood	223	(2)
Perfusion rates in human bone-marrow cultures	225	(1)
Nutrient transport in liver reactions	226	(1)
Key Design Challenges	226	(6)
Delivering oxygen	226	(3)
Delivering and removing growth factors	229	(2)
Delivering nutrients and removing waste products	231	(1)
Fluid Flow	232	(3)
Uniformity	232	(2)
Residence-time distributions	234	(1)
Cellularity	235	(3)
Geometry of the Microenvironment	238	(1)
Multivariable Optimization	239	(2)
Controllable cell-culture variables	239	(2)
Biological differences among individuals	241	(1)
Summary	241	(2)
Further Reading	243	(1)
Cell Separation	244	(8)
Basis for Cell Separation	244	(1)
Physical properties	244	(1)
Biochemical properties	245	(1)
Characterizing Cell Separation	245	(1)
Practiced Cell-Separation Methods	246	(4)
Treating populations of cells	246	(3)
Treating cells individually	249	(1)
Summary	250	(1)
Further Reading	251	(1)
Biomaterial Scaffolds	252	(18)
Biomaterial Properties	252	(9)
Surface properties	252	(4)
Bulk properties	256	(1)
Mechanical properties	256	(2)
Biological properties	258	(3)
Types of Biomaterials	261	(8)
Biologic materials	261	(1)
Synthetic materials	262	(7)
Summary	269	(1)
Further Reading	269	(1)
Tailoring Biomaterials	270	(20)
Tailoring Surface Chemistry and Topography	270	(2)
Subcellular Length Scale ( < 10 μm)	272	(5)
Surface chemistry	272	(2)
Bulk chemistry	274	(1)
Surface topography	275	(2)
Cellular Scale (10--100 μm)	277	(8)
Surface chemistry	278	(2)
Topography	280	(5)
Supracellular Scale (100 μm-1 cm)	285	(1)
Influence of chemistry	285	(1)
Influence of architecture	285	(1)
Supracellular scale processing	285	(1)
Functions of Tailored Biomaterials	286	(1)
Summary	286	(1)
Further Reading	287	(3)
Part IV Clinical Implementation
Conventional Clinical Approaches to Tissue Dysfunction	290	(13)
Medical Therapies for Tissue Dysfunction	290	(1)
Surgical Therapies for Tissue Dysfunction	291	(6)
Repair	291	(1)
Replacement	292	(3)
Reconstruction from an alternative tissue type	295	(1)
Removal	296	(1)
Temporary Support Using Extracorporeal Devices	297	(1)
Tissue-Engineered Therapies	297	(5)
Mesodermal tissue case study: articular cartilage	297	(2)
Ectodermal tissue case study: skin	299	(2)
Endodermal tissue case study: liver	301	(1)
Summary	302	(1)
Further Reading	302	(1)
Host Integration: Interacting Cell-Fate Processes	303	(17)
Wound-Healing Response	303	(2)
Hemostasis (seconds to minutes)	304	(1)
Inflammation (minutes to days)	304	(1)
Proliferative phase (days to weeks)	304	(1)
Remodeling phase (weeks to year)	305	(1)
Angiogenesis	305	(3)
Basic process	306	(1)
Modifying angiogenesis	307	(1)
Immune Response	308	(9)
Basics	308	(2)
Characteristic numbers	310	(2)
Mechanisms of graft rejection	312	(2)
Immune response in tissue engineering	314	(1)
Strategies for modifying the immune response	315	(2)
Summary	317	(2)
Further Reading	319	(1)
Producing Tissue-Engineered Therapies	320	(15)
Product Characterization	320	(5)
Components	320	(1)
Safety	321	(3)
Efficacy	324	(1)
Preservation	325	(5)
Freezing	325	(3)
Drying	328	(2)
Patent Protection	330	(1)
Regulation of Tissue-Engineered Products	331	(2)
Ethical Issues	333	(1)
Summary	334	(1)
Further Reading	334	(1)
A Tissue-Engineering Study Problems	335	(40)
Part I: Quantitative Cell and Tissue Biology	335	(23)
Part II: Cell and Tissue Characterization	358	(4)
Part III: Engineering Methods and Design	362	(9)
Part IV: Clinical Implementation	371	(4)
References	375	(22)
Index	397

Excerpts

Tissue engineering holds the promise to repair or replace damaged organs. As a discipline, the field has evolved dramatically from its origins in the late 1980s. In particular, the rapid advances in stem cell biology have rekindled the enthusiasm use cell-based approaches for the treatment of disease. For success in this area, must learn to manipulate, produce, and deliver collections of cells as building blocks of tissues. Transplanted cells and tissue constructs are influenced by their microenvironment and can be manipulated to effectively interact with patients. The underpinnings of tissue engineering are thus broad, and span a wide spectrum of scientific and engineering fundamentals. This list includes basic biological sciences (cell biology, physiology, embryology, and wound healing); engineering fundamentals (fluid dynamics, transport phenomena, materials science, mechanics, and chemical kinetics); many clinical aspects (surgery and transplantation, immunology, pathology, radiology, and medicine), and various relevant biotechnologies (cell culture, cell separation, and gene transfer). This long list of specialized knowledge makes it challenging to organize all the necessary background material for the student of tissue engineering in a clear and succinct manner. In writing this book, we aimed to lay the foundation for students studying tissue engineering at both the undergraduate and the graduate level. We have attempted to provide a conceptual framework that includes exposure to all of the necessary background material. Thus, we cannot treat any particular subject in great detail but rather can provide the needed conceptual background in all areas. Instructors will find this text to be a useful framework since it is amenable to augmentation based on the instructors area of expertise and desired focus of a course in tissue engineering. The text is written primarily for senior bioengineering students or first-year graduate students and assumes a working knowledge of the engineering fundamentals. In this spirit, we have provided a series of engineering-style homework problems and solutions in order to allow students to work through the concepts presented. Nonetheless, we also hope that the text will be useful to traditional engineering students, material scientists, medical students, laypeople, and biologists. We have chosen to present the material in four parts: quantitative cell and tissue biology, cell and tissue characterization, engineering methods and design, and clinical implementation. Throughout the text, we have emphasized relevant time and length scales of physicochemical processes in cell biology and medicine. Armed with these fundamentals, we seek to have students establish a conceptual framework within which to place further advances in the field. Many societal and technical challenges still remain for the field to move forward, and we have highlighted these to the extent possible. Writing a textbook like this one is a significant undertaking. There are many individuals and organizations to thank for helping us with various aspects of the writing process. The Whitaker Foundation generously provided financial support for this project through their Teaching Materials program. Their recognition that textbooks are required to build consensus and firmly establish a field will be an important part of their legacy. Two individuals were key in preparing this text. Marc Abrams tirelessly assisted in compiling all aspects of this text and prepared it using LATEX, which made the production and publication an easier process. Salman Khetani made heroic efforts in reading all of the material in detail and offering perceptive criticism, suggestions, and input that significantly improved the quality of the text. He and Valerie Liu provided important feedback on their experience teaching from this text and help with preparing homework problems. Christophe Schilling, Ramprasad Ramakrishna, Jason Papi