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Summary
Summary
Highly Commended at the BMA Book Awards 2013
Extreme Tissue Engineering is an engaging introduction to Tissue Engineering and Regenerative Medicine (TERM), allowing the reader to understand, discern and place into context the mass of scientific, multi-disciplinary data currently flooding the field. It is designed to provide interdisciplinary, ground-up explanations in a digestible, entertaining way, creating a text which is relevant to all students of TERM regardless of their route into the field.
Organised into three main sections: chapters 1 to 3 introduce and explain the general problems; chapters 4 to 6 identify and refine how the main factors interact to create the problems and opportunities we know all too well; chapters 7 to 9 argue us through the ways we can use leading-edge (extreme) concepts to build our advanced solutions.
Students and researchers in areas such as stem cell and developmental biology, tissue repair, implantology and surgical sciences, biomaterials sciences and nanobiomedicine, bioengineering, bio-processing and monitoring technologies - from undergraduate and masters to doctoral and post-doctoral research levels - will find Extreme Tissue Engineering a stimulating and inspiring text.
Written in a fluid, entertaining style, Extreme Tissue Engineering is introductory yet challenging, richly illustrated and truly interdisciplinary.
Author Notes
Robert A. Brown is Professor of Tissue Engineering and Director of the Centre for Tissue Regeneration Science at University College London, UK. He is also co-ordinator of the London Tissue Engineering Consortium (Tissue Bioreactor Science) and the British Tissue Engineering Network (BRITE Net), as well as current President of the Tissue and Cell Engineering Society (TCES). Professor Brown has published over 180 peer-reviewed publications and 18 patents/applications, collaborating across industry and academia to promote interdisciplinary research in Tissue Engineering and Regenerative Medicine
Table of Contents
Preface: Extreme Tissue Engineering - a User's Guide | p. xi |
1 Which Tissue Engineering Tribe Are You From? | p. 1 |
1.1 Why do we need to engineer tissues at all? | p. 1 |
1.1.1 Will the real tissue engineering and regenerative medicine please stand up? | p. 2 |
1.1.2 Other people's definitions | p. 3 |
1.1.3 Defining our tissue engineering: fixing where we are on the scale-hierarchy | p. 4 |
1.2 Bio-integration as a fundamental component of engineering tissues | p. 7 |
1.2.1 Bio-scientists and physical scientists/engineers: understanding diversity in TERM | p. 8 |
1.3 What are the 'tribes' of tissue engineering? | p. 10 |
1.3.1 Special needs for special characteristics: why is networking essential for TERM? | p. 13 |
1.4 Surprises from tissue engineering (Veselius to Vacanti) | p. 16 |
1.5 So, really, is there any difference between tissue engineering and regenerative medicine? | p. 20 |
1.5.1 Questions never really asked: repair versus regeneration? | p. 20 |
1.5.2 Understanding the full spectrum: tissue replacement, repair and regeneration | p. 23 |
1.6 Conclusions | p. 27 |
1.7 Summarizing definitions | p. 28 |
Annex 1 Other people's definitions of tissue engineering | p. 29 |
Annex 2 Other people's definitions of regenerative medicine | p. 30 |
Further reading | p. 30 |
2 Checking Out the Tissue Groupings and the Small Print | p. 33 |
2.1 Checking the small print: what did we agree to engineer? | p. 33 |
2.2 Identifying special tissue needs, problems and opportunities | p. 37 |
2.3 When is 'aiming high' just 'over the top'? | p. 39 |
2.4 Opportunities, risks and problems | p. 41 |
2.4.1 Experimental model tissues (as distinct from spare-parts and fully regenerated tissues) | p. 41 |
2.4.2 The pressing need for 3D model tissues | p. 42 |
2.4.3 Tissue models can be useful spin-offs on the way to implants | p. 42 |
2.5 Special needs for model tissues | p. 44 |
2.5.1 Cell selection: constancy versus correctness | p. 44 |
2.5.2 Support matrices - can synthetics fake it? | p. 45 |
2.5.3 Tissue dimensions: when size does matter! | p. 46 |
2.6 Opportunities and sub-divisions for engineering clinical implant tissues | p. 46 |
2.6.1 Making physiological implants: spare parts or complete replacement? | p. 47 |
2.6.2 Making pathological and aphysiological constructs: inventing new parts and new uses | p. 47 |
2.6.3 Learning to use the plethora of tissue requirements as an opportunity | p. 48 |
2.7 Overall summary | p. 49 |
Further reading | p. 49 |
3 What Cells 'Hear' When We Say '3D' | p. 51 |
3.1 Sensing your environment in three dimensions: seeing the cues | p. 51 |
3.2 What is this 3D cell culture thing? | p. 54 |
3.3 Is 3D, for cells, more than a stack of 2Ds? | p. 55 |
3.4 On, in and between tissues: what is it like to be a cell? | p. 58 |
3.5 Different forms of cell-space: 2D, 3D, pseudo-3D and 4D cell culture | p. 62 |
3.5.1 What has '3D' ever done for me? | p. 62 |
3.5.2 Introducing extracellular matrix | p. 63 |
3.5.3 Diffusion and mass transport | p. 65 |
3.5.4 Oxygen mass transport and gradients in 3D engineered tissues: scaling Mount Doom | p. 66 |
3.6 Matrix-rich, cell-rich and pseudo-3D cell cultures | p. 69 |
3.7 4D cultures - or cultures with a 4th dimension? | p. 71 |
3.8 Building our own personal understanding of cell position in its 3D space | p. 73 |
3.9 Conclusion | p. 75 |
Further reading | p. 75 |
4 Making Support-Scaffolds Containing Living Cells | p. 77 |
4.1 Two in one: maintaining a synergy means keeping a good duet together | p. 77 |
4.2 Choosing cells and support-scaffolds is like matching carriers with cargo | p. 78 |
4.3 How like the 'real thing' must a scaffold be to fool its resident cells? | p. 80 |
4.4 Tissue prosthetics and cell prosthetics - what does it matter? | p. 83 |
4.5 Types of cell support material for tissue engineering - composition or architecture? | p. 85 |
4.5.1 Surface or bulk - what does it mean to the cells? | p. 85 |
4.5.2 Bulk material breakdown and the local 'cell economy' | p. 85 |
4.6 Three generic types of bulk composition for support materials | p. 86 |
4.6.1 Synthetic materials for cell supports | p. 88 |
4.6.2 Natural, native polymer materials for cell supports | p. 90 |
4.6.3 Hybrids: composite cell support materials having synthetic and natural components | p. 98 |
4.7 Conclusions | p. 100 |
Further reading | p. 101 |
5 Making the Shapes for Cells in Support-Scaffolds | p. 103 |
5.1 3D shape and the size hierarchy of support materials | p. 104 |
5.2 What do we think 'substrate shape' might control? | p. 106 |
5.3 How we fabricate tissue structures affects what we get out in the end: bottom up or top down? | p. 107 |
5.4 What shall we seed into our cell-support materials? | p. 110 |
5.4.1 Cell loading: guiding the willing, bribing the reluctant or trapping the unwary? | p. 111 |
5.4.2 Getting cells onto/into pre-fabricated constructs (the willing and the reluctant) | p. 114 |
5.4.3 Trapping the unwary: Seeding cells into self-assembling, gel-forming materials | p. 115 |
5.5 Acquiring our cells: recruiting the enthusiastic or press-ganging the resistant | p. 118 |
5.5.1 From cell expansion to selection and differentiation | p. 121 |
5.6 Cargo, crew or stowaway? | p. 124 |
5.6.1 Crew-type cells: helping with the journey | p. 124 |
5.6.2 Cargo-type cells: building the bulk tissue | p. 125 |
5.6.3 Stowaway or ballast-type cells | p. 128 |
5.7 Chapter summary | p. 128 |
Further reading | p. 129 |
6 Asymmetry: 3D Complexity and Layer Engineering - Worth the Hassle? | p. 131 |
6.1 Degrees of tissue asymmetry | p. 133 |
6.2 Making simple anisotropic/asymmetrical structures | p. 134 |
6.3 Thinking asymmetrically | p. 137 |
6.4 How do we know which scale to engineer first? | p. 140 |
6.5 Making a virtue of hierarchical complexity: because we have to | p. 144 |
6.6 Cell-layering and matrix-layering | p. 147 |
6.7 No such thing as too many layers: theory and practice of tissue layer engineering | p. 151 |
6.7.1 Examples of layer engineering | p. 153 |
6.8 Other forms of tissue fabrication in layers and zones | p. 158 |
6.8.1 Section summary | p. 158 |
6.9 Familiar asymmetrical construction components: everyday 'layer engineering' | p. 159 |
6.10 Summary | p. 160 |
7 Other Ways to Grow Tissues? | p. 163 |
7.1 General philosophies for repair, replacement and regeneration | p. 163 |
7.1.1 What does reconstructive surgery have to teach us? | p. 165 |
7.1.2 Clues from the natural growth of tissues | p. 166 |
7.2 What | |
Part of grow do we not understand? | p. 167 |
7.2.1 Childhood growth of soft connective tissues: a good focus? | p. 169 |
7.2.2 Mechanically induced 'growth' of tissues in children | p. 170 |
7.2.3 Mechanically induced 'growth' of adult tissue | p. 171 |
7.2.4 Growth has a mirror image - 'ungrowth' or shrinkage-remodelling | p. 172 |
7.3 If growth and ungrowth maintain a tensional homeostasis, what are its controls? | p. 173 |
7.3.1 Tension-driven growth and tensional homeostasis - the cell's perspective? | p. 174 |
7.3.2 Mechanically reactive collagen remodelling - the 'constant tailor' theory | p. 177 |
7.4 Can we already generate tension-driven growth in in vivo tissue engineering? | p. 178 |
7.4.1 Mechanical loading of existing tissues | p. 178 |
7.5 Conclusions: what can we learn from engineered growth? | p. 179 |
Appendix to Chapter 7 | p. 179 |
Further reading | p. 182 |
8 Bioreactors and All That Bio-Engineering Jazz | p. 185 |
8.1 What are 'tissue bioreactors' and why do we need them? | p. 186 |
8.1.1 Rumblings of unease in the smaller communities | p. 186 |
8.1.2 Hunting for special cells or special cues | p. 187 |
8.1.3 Farming - culture or engineered fabrication | p. 188 |
8.2 Bioreactors: origins of tissue bioreactor logic, and its problems | p. 190 |
8.2.1 What have tissue engineers ever done for bioreactor technology? | p. 190 |
8.2.2 The 3D caveat | p. 191 |
8.2.3 Fundamental difference between biochemical and tissue bioreactors: 3D solid material fabrication | p. 193 |
8.2.4 Why should a little thing like 'matrix' change so much? | p. 194 |
8.2.5 The place of tissue bioreactors in tissue engineering logic: what happened to all the good analogies? | p. 195 |
8.3 Current strategies for tissue bioreactor process control: views of Christmas past and present | p. 199 |
8.3.1 Bioreactor enabling factors | p. 200 |
8.3.2 Cell and architecture control | p. 203 |
8.4 Extreme tissue engineering solutions to the tissue bioreactor paradox: a view of Christmas future? | p. 209 |
8.4.1 In vivo versus in vitro tissue bioreactors: the new 'nature versus nurture' question? | p. 209 |
8.4.2 Do we need tissue bioreactors at all? | p. 210 |
8.5 Overall summary - how can bioreactors help us in the future? | p. 212 |
Further reading | p. 214 |
9 Towards 4D Fabrication: Time, Monitoring, Function and Process Dynamics | p. 217 |
9.1 Controlling the dynamics of what we make: what can we control? | p. 218 |
9.2 Can we make tissue bioreactor processes work - another way forward? | p. 222 |
9.2.1 Blending the process systems: balancing the Yin and the Yang | p. 224 |
9.2.2 Making the most of hybrid strategies: refining the timing and sequence | p. 226 |
9.2.3 A real example of making tissues directly | p. 230 |
9.3 The 4th dimension applied to bioreactor design | p. 232 |
9.3.1 Change, change, change! | p. 232 |
9.3.2 For bioreactor monitoring, what are we really talking about? | p. 233 |
9.3.3 Monitoring and processes - chickens and eggs: which come first? | p. 234 |
9.4 What sort of monitoring: how do we do it? | p. 238 |
9.4.1 Selecting parameters to be monitored | p. 238 |
9.4.2 What is so special about our particular 'glass slipper'? | p. 241 |
9.5 The take-home message | p. 245 |
Further reading | p. 246 |
10 Epilogue: Where Can Extreme Tissue Engineering Go Next? | p. 247 |
10.1 So where can extreme tissue engineering go next? | p. 247 |
Index | p. 249 |