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Tables of Contents for Tissue and Organ Regeneration in Adults
Chapter/Section Title
Page #
Page Count
Preface
vii
Acknowledgments
xi
The Irreversibility of Injury
1
25
Repair versus Regeneration
1
1
Tissues and Organs
1
1
Spontaneous and Induced Regeneration
2
1
Diversity of Spontaneously Regenerative Phenomena
3
2
Anatomical and Phylogenetic Focus of Regeneration
5
1
Wounds, Lesions, and Defects
6
1
All Organs Can Be Irreversibly Injured
6
3
Critical Size of Defect versus Nature of Injured Tissue
9
4
A Universal End Product of Repair Processes in All Organs?
13
2
Theoretical Views of Adult Failure to Regenerate
15
3
The Missing Organ and How to Replace It
18
5
Transplantation
19
1
Autografting
20
1
Permanent Prosthesis
20
1
Stem Cells
21
1
In Vitro Synthesis
21
1
Induced Organ Regeneration
22
1
Synthesis of Tissues and Organs
23
2
Summary
25
1
Nonregenerative Tissues
26
25
The Experimental Volume: In Vitro or In Vivo?
26
1
Critical Presence of Exudate Inside the Defect
27
1
Certain Tissues in an Organ Regenerate Spontaneously
28
8
Epitheliocentric Viewpoint
29
2
Axonocentric Viewpoint
31
4
Spontaneously Regenerative Tissues
35
1
Other Tissues Are Nonregenerative
36
7
The Dermis Is Nonregenerative
36
1
The Endoneurial Stroma Is Nonregenerative
37
2
Evidence for and Against Regeneration of Other Nonneuronal Tissues
39
2
The Supporting Tissue (Stroma) of Several Organs Is Nonregenerative
41
2
Are Basement Membranes Regenerative?
43
1
Regenerative Similarity of Tissues in Different Organs
44
2
The Tissue Triad
46
3
Summary
49
2
Anatomically Well-Defined Defects
51
12
Spatial Parameters of an Experiment in Induced Regeneration
51
1
Generation of the Experimental Volume
52
1
Deletion of Nonregenerative Tissues
53
1
Anatomical Boundaries
54
3
Magnitude of Experimental Volume
57
2
Physical Containment
59
1
The Anatomically Well-Defined Defect
60
1
Widely Used Animal Models
60
2
Summary
62
1
The Defect Closure Rule
63
30
Measuring the Outcome of a Regenerative Process
63
1
Mechanism of Healing versus Total Resulting Change
64
1
Initial and Final States of a Healing Process
65
4
Configuration of the Final State
69
1
Three Modes of Defect Closure in Organs
70
12
Closure of Defects in Organs by Contraction
70
6
Measurement of Contraction in Skin and Nerve Defects
76
1
Closure by Epithelialized Scar (Skin) and by Neuroma (Nerve)
77
5
Closure by Regeneration
82
1
Defect Closure Rule
82
2
Relative Importance of the Three Modes of Defect Closure in Different Species
84
4
A Transition in Healing Behavior with Development
88
3
Summary
91
2
Regeneration of Skin
93
45
Parameters for Study of Healing Skin Defects
93
2
Anatomically Well-Defined Skin Defects
94
1
Timescale of Observations
94
1
Assays of Configuration of the Final State
95
1
Synthesis of an Epidermis and a Basement Membrane
95
15
Morphology and Function of the Epidermis
96
1
Synthesis of an Epidermis In Vitro
96
3
Structure of Basement Membranes
99
2
Synthesis of a Skin Basement Membranes
101
4
Origins of Mechanical Failure of the Dermo-Epidermal Junction
105
4
Synthetic Potential and Limitations of Keratinocyte Sheet Grafts
109
1
Synthesis of the Dermis
110
5
Structure and Function of the Dermis
110
1
Sequential In Vivo Synthesis of a Dermis and an Epidermis
111
4
Synthetic Potential and Limitations of the Cell-Free Dermis Regeneration Template
115
1
Partial Synthesis of Skin
115
14
Structure and Function of Skin
115
1
Simultaneous Synthesis of a Dermis and an Epidermis
116
6
Distinction Between In Vitro and In Vivo Synthesis
122
1
In Vitro to In Vivo Synthetic Routes
123
4
Evidence for Synthesis of a Partly Complete Skin Organ
127
2
Summary of Protocols
129
3
Simplest Conditions for Synthesis
132
1
Relative Regenerative Activity of Growth Factors, Cells, and Scaffolds
133
4
Summary
137
1
Regeneration of a Peripheral Nerve
138
48
Parameters for Study of Peripheral Nerve Regeneration
138
13
Anatomically Well-Defined Defects in Peripheral Nerves
139
1
Timescale of Observations: Short-Term and Long-Term Assays
139
3
Short-Term Quantitative Assays (< 20 wk): Frequency of Reinnervation <20 wk): Frequency of Reinnervation
142
1
Correction for Differences in Gap Length and Animal Species: Critical Axon Elongation
143
3
Relation Between Critical Axon Elongation Data and the Defect Closure Rule
146
3
Long-Term Assays (>20 wk): Fidelity of Regeneration
149
1
Summary Description of Assays
149
2
Synthesis of Myelinated Nerve Fibers
151
8
Structure of Myelinated and Nonmyelinated Axons and of the Endoneurium
152
3
Synthetic Pathways to Myelinated Axons and Basement Membrane
155
2
Observations Related to Synthesis of an Endoneurial Stroma
157
2
Synthesis of a Perineurium; the Epineurium
159
5
Structure and Function of the Perineurium
159
2
The Epineurium
161
1
In Vitro and In Vivo Studies of Synthesis of a Perineurium
162
2
Synthesis of a Nerve Trunk
164
19
Exogenous Supply of Soluble Regulators
164
3
Schwann Cell Addition to the Tubulated Gap
167
1
Filled and Unfilled Silicone Tubes
168
4
Biodurable Tubes Other than Silicone Tubes
172
1
Degradable Synthetic Polymeric Tubes
172
3
Degradable Tubes Based on Natural Polymers
175
4
Semipermeable Tubes
179
2
Long-Term Evidence for Synthesis of a Conducting Nerve Trunk
181
2
Regenerative Activity for Various Tubulated Configurations
183
1
Summary
184
2
Irreducible Processes for Synthesis of Skin and Peripheral Nerves
186
33
Reaction Diagrams
186
15
Reactants and Products: Irreducible Processes
187
1
Approximations Underlying the Use of Reaction Diagrams
188
5
Tabulation of Reaction Diagrams
193
8
Irreducible Reaction Diagrams for Synthesis of Skin
201
4
In Vitro versus In Vivo Conditions
205
3
Conditions for Synthesis of Peripheral Nerves
208
3
A Fresh Look at the Tissue Triad
211
3
Toward Simple Protocols for Synthesis of the Entire Organ
214
2
Summary
216
3
The Antagonistic Relation Between Contraction and Regeneration
219
25
Contraction and Scar Formation Versus Induced Regeneration
219
15
Reduction in Extent of Contraction in the Final State Coincided with Induced Regeneration
220
5
Delay in Closure by Contraction in Regenerating and Nonregenerating Defects
225
2
Spontaneously Healing Defects: Relation Between Contraction and Regeneration
227
2
Scar Synthesis Was Abolished When Contraction Was Inhibited
229
1
Suppression of Contraction Did Not Suffice to Induce Regeneration
229
4
Summary of Data; a Theory Relating Inhibition of Contraction and Induction of Regeneration
233
1
Nondiffusible Regulators as Probes of Contraction
234
8
Diffusible and Nondiffusible Regulators
234
1
Nondiffusible Regulators Are Insoluble Macromolecular Solids
234
1
Homologous Series of ECM Analogs as Probes of Induced Regeneration
235
1
Biological Activity of Certain ECM Analogs
236
3
Strong Dependence of Contraction-Delaying Activity on Structure of ECM Analogs
239
3
Summary
242
2
Kinetics and Mechanism I: Spontaneous Healing
244
34
Mechanism versus Final State of Spontaneous Healing
244
1
Cell Phenotypes Exhibited During Spontaneous Healing
244
3
Go-Stop Signals for Skin Defect Closure in Adults
247
20
Injury to the Dermis: A Signal for Generation of the Cytokine Field
247
2
Synthesis of a Provisional Matrix and of Granulation Tissue
249
1
Identity of Contractile Cells
250
3
Generation of Local Stress by an Individual Contractile Cell
253
1
Mechanisms of Closure by Contraction
254
4
Directional Closure of Defects; Translation of Perilesional Dermis
258
1
Synthesis of Scar
259
1
Mechanism of Contraction Arrest
260
6
Summary of Mechanisms for Initiation, Propagation, and Termination of Skin Defect Contraction
266
1
Skin Defect Closure in Fetal Models
267
2
Spontaneously Healing Defects in Peripheral Nerves
269
7
Signal for Irreversible Healing Response of a Peripheral Nerve
270
1
Proximal Stump; Traumatic Degeneration of the Myelin Sheath
271
1
Sprouting of Axons from the Proximal Stump; Minifasciculation
272
1
Long-Term Degenerative Processes in the Distal Stump
272
1
Fibrosis and Angiogenesis in the Stump
273
1
Presence of Myofibroblasts in Peripheral Nerve Stumps
273
1
Mechanism of Closure of Nerve Stump
274
1
Healing of the Nerve Defect in the Fetal Model
275
1
Summary
276
2
Kinetics and Mechanism II: Induced Regeneration
278
44
Induced Regeneration versus Spontaneous Healing
278
1
Kinetics of Skin Regeneration
278
6
Kinetics of Synthesis of the Epidermis and Basement Membrane
279
3
Synthesis of Rate Ridges and the Dermis
282
2
Synchronization Between the Processes for Synthesis of Epithelia and Stroma
284
1
Mechanism of Synthesis of the Dermis
284
15
Depletion of Cells, Including Contractile Cells, in the Defect
285
1
Delay in Onset of Contraction
286
4
Delay in Contraction Half-Life
290
4
Persistence of the Regulator in a Nondiffusible State
294
2
Mechanism for Contraction Arrest
296
2
Blocking of Scar Synthesis. Synthesis of the Dermis
298
1
Summary: Mechanism of Induced Regeneration of the Dermis
298
1
Kinetics of Synthesis of Peripheral Nerves
299
6
Synthesis of Regenerative Tissues: Nerve Fibers
300
3
Evidence for Synthesis of an Endoneurium and a Perineurium
303
2
Mechanism of Peripheral Nerve Regeneration
305
15
Length and Diameter of Regenerated Nerve Trunk
305
1
Contractile Cell Capsule Around Stumps and Regenerated Nerve Trunk
306
4
The Pressure Cuff Hypothesis
310
1
Dependence of Lc on Macroscopic Experimental Configurations
311
3
Hypothetical Synthesis of Basement Membrane Microtubes
314
2
Substrate Preferences of Schwann Cells and Elongating Axons
316
2
Mechanistic Considerations for Synthesis of Nonregenerative Tissues in Nerves
318
1
Summary of Mechanisms for Nerve Regeneration
319
1
Similarities and Differences of Induced Regeneration in Skin and Nerves
320
2
Appendix Method of Estimation of Critical Axon Elongation of an Arbitrary Tubulated Device Bridging Two Nerve Stumps
322
6
References
328
39
Index
367