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Index
AcroFlex disc, 160, 164t
activL, 160t
adalimumab, 145
ADAMTS, 8, 16–17, 101
adipose-derived stem cells (ADSCs), 114, 116, 117, 134t
Adkisson, H. D., 186
adult stem cell, 194. see also stem cells
afferent neuron, 192
aggrecan, 6, 105
Akeda, K., 105, 144
alendronate, 91t
alginate, 131, 131f, 132t
Alkhatib, B., 70
allogenic, 194
allograft, 195
Allon, A. A., 114
animal models
anatomy, 38, 39–41f
biochemical composition, 38–39, 42t
biomechanics, 39, 42t,71
bipedalism, 41–43
cells, 43, 43t
degenerative phenotype, 43–44
disc size, 38–39, 39f,42f,42t, 43, 71
efficacy of, 44–45
grading, 49
imaging, 41
limitations of, 106–107, 178
organ culture, 66t,71
overview, 38, 45
pain-related behavior, 44
surgical considerations, 40–41
of total disc transplantation, 150–152
transport, 39– 41, 42–43f
annulus fibrosis repair
alginate, 131, 131f, 132t
anatomy, 3f,6,7f,13f
animal models, 39, 42t
autografting, 150–152, 151–153f
biological replacements, 61
biologics therapy, 79, 82, 87, 133–135, 134t
biomaterials, 131
biomechanics, 30–31, 31f
cell-based therapies in, 135–136
cells, 4
closure implants, 129, 130f, 130t
collagen, 131, 131f, 132t
defined, 192
discectomy, 128–129, 128f
disc regeneration, 54
disruption, MRI, 23, 23f
–133, 131f, 132t
fibrin injection, 131, 131f, 132t
grading, 49, 50–51t
hydrogel culture systems, 57f,58
hydrogels in, 131, 131f, 132t, 133, 135
injury, causes of, 129
malic acid, 132t, 133
monolayer culture, 56, 57f, 60, 193
organ culture, 59, 59f,69–70, 69f
PCL, 132t, 133
PDLLA/45S5 bioglass, 132t, 133
PPCLM, 133
PTMC-PU, 132t, 133
PU-PCL, 132t
repair, clinical challenges in, 130
repair devices, 129, 130f, 130t
repair strategies, 128–129f, 128–130, 130t
scaffold systems, 57f, 58, 70, 193
silk, 131f, 132t
anti–TNF-α, 144–145
Antoniou, J., 48
arc of motion, 195
articular cartilage lesions, 82–83, 83t
autograft, 195
autografting
allograft biology, 154, 155f
animal models, 150–151
clinical applications, 155– 156
clinical trials, 148, 150–152, 152f
cryopreservation protocols, 152–153, 153f, 195
fresh frozen allograft, 151, 151f
graft posit ioning, 154
sterilization, 153–154
surgical technique, goat, 154–155, 156f
autologous chondrocyte implantation (ACI), 83–84, 83t,
84f
autologous chondrocyte transplantation
clinical application, 123– 124, 124f
clinical trials, 145–146
efficacy analysis, 124–126, 125f
overview, 121–122, 126
patient selection, 123, 126
preclinical study, in dog, 122, 122–123f
autologous transplant, 194
baboon, 39, 42t,43
Barr, J. S., 128
Barricaid, 129, 130f, 130t
Bergknut, N., 49
Bernardo, M. E., 117
bFGF, 101t, 103
BioCart II, 83t, 84, 85t
197
Index
biologics. see also technologies
advantages, disadvantages, 78
annulus fibrosis repair, 79, 82, 87, 133– 135, 134t
articular cartilage lesions, 82–83, 83t
autologous chondrocyte implantation (ACI), 83–84,
83t,84f
cartilaginous tissue relevant to, 82
catabolic events, 76
cell anabolism stimulation, 77
cell function, phenotype deterioration, 77
clinical trials, approaches to, 141f, 145f, 148
clinical trials regulatory framework, 172–173, 173t
disease stage considerations, 77, 77t
donor sites, 87
ear, nose cartilage, 86
effective strategy design, 79
fixation, 87
history of, 76, 78–79, 78f,82
inflammation control, 76, 82
intervention suitability, 79–80
mechanical strength/function, 76–77
meniscus, autologous concentrates, 84–86, 85f,86t
microenvironment reconstruction, 77
motion segment unit deformation, 77–78
nanoscale anomalies, 77
prophylactics, 80
regulatory framework, 171
screening, monitoring, 80
spine-specific challenges, 86–87
treatment goals, 76
Biologics Control Act of 1902, 170
Biologics License Application (BLA), 174, 195
biomaterials, 131–133, 131f, 132t
biomechanics
animal models, 39, 42t,71
annular tears, clefts, 33–34
annulus fibrosus, 30–31, 31f
of healthy disc, 30–31, 31f,32t
historical perspective, 30
instability, 33–34, 186, 192
morphological, tissue composition changes, 32–33, 33f
nucleus pulposus, 30–31, 31f
radiological changes, 31–32
of spine, normal, 159, 159–
terminology, 192–193
bioreactor systems, 67–69, 68f, 71, 193, 194
bipedal, 195
bisphosphonates, 93
black disc, 32
BMP, 61, 79
BMP-2, 97t, 102–103t, 105
BMP-7, 97t, 105–106, 106f, 121, 134t, 135, 154. see also
OP-1
Bonassar, L., 185
bone marrow, 194
bone marrow aspirate concentrate (BMAC), 85
160f
bone marrow–concentrated cells (BMCs), 145f, 146
bone marrow stem cell (BMSC), 111t, 114, 141t, 194
Boos, N., 48, 49, 50t
Borelli, Giovanni Alfonso, 30
breakthrough product, 195
Bryan disc, 162, 163t, 166
calf, 39, 42f,42t,43
Carticel, 83, 83t,85t
CCL5, 71, 134t, 135
cell-based therapies
in annulus fibrosis repair, 135–136
challenges, risks, 117
clinical trials, 145–148, 147f
costs of, 188
FDA approval of, 174
ideal cell types, 110–113, 111–112t, 112f
MSCs (see mesenchymal stem cells (MSCs))
overview, 110, 111f, 117
target tissue, 115–116, 115f
terminology, 111–112t
cell phenotype, 193
cell source, 193
Center for Biologics Evaluation and Research (CBER), 170,
171, 195
Center for Drug Evaluation and Research (CDER), 171
ceramics, 162–163
Chan, S. C., 69
Charité III, 161–162, 161f, 163–164
chemokines, 192
chemotaxis, 194
Chen, W. H., 105
Chiba, K., 67
Choi, E. H., 114
chondroadherin, 6
chondrocytes, 56, 82, 111t, 113, 113–114t, 134t, 147, 194.
see also autologous chondrocyte implantation (ACI)
chondroitinase-ABC (C-ABC), 185
clinical trials
anti–TNF-α, 144–145
autologous chondrocyte transplantation, 145–146
biological approaches, 141f, 145f, 148, 178
bone marrow–concentrated cells (BMCs), 145f, 146
cell-based therapies, 145–148, 147f
disc herniation, 151–152, 153f
gene therapy, 148
history, summary of, 140, 141–144t, 145f
mesenchymal stem cells (MSCs), 141t, 146–147
Phase I/II/III, 172–173, 196
platelet-rich plasma, 144
regulatory framework, 172–173, 173t
regulatory pathway, 179–180 (see also regulatory
framework)
stem cells, 113–114t
tissue implantation, 141f, 141t, 147–148
total disc arthroplasty, 166–167
t
198
Index
total disc transplantation, 148, 150–152, 152f
collagens
animal models, 43
annulus fibrosis repair, 131, 131f, 132t
culture systems, 57f,70
human, 5, 7, 13, 14
PRP effects on, 105
composite disc constructs, 58–59, 58f, 193
computational model, 192
confidentiality agreement (CA), 179, 196
Coric, D., 142–143t
coupled motion, 158, 159, 159–160f
cow, 39, 42–43t,42f,43
Crohn’s disease, 79
cryopreservation, 152–153, 153f, 195
culture systems, 56–59, 57–59f,66t. see also specific sys-
tems
Cummins-Bristol disc, 161
CXCL10, 134t, 135
cytokines. see inflammatory cytokines
Dandy, W. E., 128
degenerative disc disease, 192
DeNovo NT, 83t, 84, 85t
DePuy Spine, J.-C. P. L., 143–144t
differentiation, 194
diffusion tensor imaging (DTI), 20, 23, 192
diffusion-weighted imaging (DWI), 20, 23, 192
disc aging, 192
discal cyst, 26, 26f
disc degeneration pathophysiology
aggrecanases, 16–17
architectural, mechanical changes, 12–14, 13f
cell metabolism, 14
composition changes, 11–12, 12f,13t
disease, 11, 11f
immune cells, 14–
inflammatory cytokines, 14–16, 15–16f
innervation, 14
NF-κB mediated pathways, 14–17, 15–16f
nutrition, 17
proteases, 16–17
terminology, 192
disc extrusion, 21f, 24, 24f
disc herniation
biological therapy, 79, 145
clinical trials, 151–152, 153f
in degeneration pathology, 121–124, 124f, 185
gas-containing, 26
intradural, MR I, 24f,26
MRI, 21f,23–26, 24–25f
TDA therapy, 165–166
TE-IVD therapy, 147–148
traumatic, 151–152, 153f
discogenic pain, 192
disc regeneration. see also technologies
16, 15–16f
cell-based therapies (see cell-based therapies)
cell sources, 55–56
challenges in, 61
culture systems, 56–59, 57–59f,66t
glucose, 60
growth factors, 60–61
historical perspective, 54
inflammatory factors, 60
injectable therapeutics, 54
mechanical loading, 60, 61f
oxygen tension, 60
pH, 60
strategies, 54–55
terminology, 193–194
total/partial replacement, 54– 55
in vitro culture systems, 55, 57f
dislocation, 195
dog, 41f,43t, 49, 122, 122–123
Drug Pathway (FDA), 196
dual-bearing prostheses, 161– 162, 161f, 163–164t
ear, nose cartilage, 86
ectoderm, 194
electrospinning, 132t, 133
embryonic stem cells (ESCs), 55, 111t, 113, 193, 194
endoderm, 194
end plate. see vertebral end plate
extension arc, 195
extracellular matrix (ECM), 192
Farfan, H. F., 30
FDA, 174–175, 174t, 196
Federal Food,Drug, and Cosmetic Act (FDC Act) of 1938,
170
Fernström, U., 160
fibrin injection, 131, 131f, 132t
fibrous scaffold systems, 57f,58
fixed-bearing prostheses, 161, 163–164t
FlexiCore, 164t
fresh frozen allograft, 151, 151f
fully differentiated cells, 55–56, 193
functional spinal unit (FSU), 159, 159f, 192
Gantenbein, B., 67
Gawri, R., 67
GDF-5, 97t, 101–104t, 103–104, 104f, 116, 141t
GDF-6, 102t, 105
gene therapy. see also biologics
alendronate, 91t
bisphosphonates, 93
BMP-2, 97t, 102–103t, 105
BMP-7, 97t, 105–106, 106f, 121, 134t, 135, 154
clinical trials, 148
GDF-5, 97t, 101–104t, 103–104, 104f, 116, 141t
IGF-1, 97t, 101t, 103, 103t
lactoferricin, 91–92t, 93, 94f
f
199
Index
link N, 70, 92t,94–95, 96f, 103t, 134t, 135
LMP-1, 97t,98–99
lovastatin, 92t, 103t
overview, 90, 91f,99
paeoniflorin, 92t,95
Peniel 2000, 92t, 94, 95f
peptides, proteins, compounds, 90, 91–93t, 134t, 135
resveratol, 92–93t,95–96
simvastatin, 93t, 103t, 134t, 135
SOX9, 97t, 99, 115
statins, 92–93t, 93, 103t, 134t, 135
strategies, 91f, 96, 97–98t
TGF-β1, 97–98t,98
TIMP-1, 98, 98t
glycosaminoglycan (GAG)
animal models, 49
culture systems, 57f
human, 5–6, 12, 21
goat, 42t, 154–155, 156f
Good Clinical Practice (GCP), 175, 195
Good Laboratory Practice (GLP), 175, 195
Good Manufacturing Practice (GMP), 123, 175, 195
Gorensek, M., 113
grading scales
histological, 49–50, 50– 51t
overview, 48, 52–53
radiology, 50
Thompson (see Thompson grading system)
Thompson system, 13t,48–49, 49t
graft-versus-host disease, 79
growth factor injection. see also platelet-rich plasma (PRP)
animal models limitations, 106–107
in annulus fibrosis repair, 134t, 135
bFGF, 101t, 103
disc degeneration induction via, 106
in disc regeneration, 60–61
GDF-5, 97t, 101–104t, 103–104, 104f, 116, 141t
GDF-6, 102t, 105
half life of, 105–106, 106f
IGF-1, 97t, 101t, 103, 103t
injection treatment effects, 101–103, 101–103t
IVDs, nutritional supply into, 106
OP-1, 102t, 103–104, 134t, 135
patient selection, 106
placebo effects, 107
TFG-β, 101t
Gruber, H. E., 116
Gui, K., 105
Gullung, G. B., 105
Haglund, L., 68
Han, B., 49, 50t
HA-pNIPAM hydrogel, 67, 194
hard-on-hard bearings, 162–163
hard-on-soft bearings, 163– 164
Härtl, R., 185
–52, 52t, 111f
Haufe, S. M., 132t
HCT/Ps, 170–171, 180, 196
health care economics, 180
hematopoietic stem cells (HSCs), 111t, 141t, 146, 194
HGF, in vivo effects, 103
histological grading scales, 49–50, 50–51t
horse, 43t
hTERT, 154, 155f
Hukuda, S., 150
hydrogels
in annulus fibrosis repair, 131, 131f, 132t, 133, 135
culture systems, 57f, 58, 60, 67, 70, 71
defined, 193
hypoxia-inducible factor (HIF) 1-α,60
IGF-1, 97t, 101t, 103, 103t
IL receptor antagonist (IL-RA), 79
imaging. see MRI
immunocompatibility, 195
induced pluripotent stem cells (iPSCs), 55, 113–114, 193
inflammatory cytokines
animal models of, 43–44
control via biologics, 76, 82
disc degeneration pathophysiology, 14–16, 15–16f
disc regeneration, 60
infliximab, 134t, 135
injectable cell therapies, 61
instability (spinal), 33–34, 186, 192
intellectual property, 179, 196
intervertebral disc anatomy
annulus fibrosus, 3f,6,7f,13f
cells within, 3–5, 7f
development, 2–3, 4–5f
histology, 7f
matrix homeostasis, repair, 8
mechanical properties, 8, 9f
nucleus pulposus, 6, 7f,9f,13f
organization, composition, 3f,5–6
vascularization, innervation, 5–6f,8
vertebral end plate, 6–8, 7f
Investigational New Drug Application process, 171,
171–172t, 195
in vitro model systems, 193
in vitro test, 192
Japanese Orthopaedic Association (JOA) score, 152, 195
juvenile chondrocytes, 134t, 147, 184
karyopyknosis, 195
Katsuura, A., 150
Kellgren, J. H., 50
Ki-68, 70
Kim, J. S., 70
Kineflex disc, 162, 163–164t
Kirkaldy-Willis, W. H., 30
Korecki, C. L., 69
t
200
lactoferricin, 91–92t, 93, 94f
Lawrence, J. S., 50
Li, Z., 70
Likhitpanichkul, M., 70
link N, 70, 92t,94–95, 96f, 103t, 134t, 135
LMP-1, 97t,98–99
loading, 194
lovastatin, 92t, 103t
Luk, K. D. K., 150
MACI, 83t, 84, 85t
Madan, S. S., 50
malic acid, 132t, 133
Malonzo, C., 70
Maroudas, A., 67
material substrate, 193
matrix metalloproteinases (MMPs), 8, 14, 101
Maverick disc, 162, 163–164t
MAVRIC, 192
McCanless, J. D., 116
Meisel, H. J., 142t
meniscus, autologous concentrates, 84–86, 85f,86t
mesenchymal precursor cells (MPCs), 111t, 112f, 115,
146–147, 185, 194
mesenchymal stem cells (MSCs)
in annulus fibrosis repair, 134t
in biologics therapy, 79, 85
in cell-based therapy, 114
challenges, risks, 117, 121
clinical trials, 141t, 146–147
defined, 111t, 193, 194
discogenic differentiation induction, 116
growth factor induction, 116
HCT/Ps regulation, 170–171, 180
in organ culture, 55, 57f, 60, 67, 70–71
Mesoblast Ltd., 144t, 146, 185
mesoderm, 194
Mimura, M., 50
mitogen-activated protein kinase (MAPK), 70
Miura, M., 117
Mixter, W. J., 128
Mobi-Cb, 163t
MOM prostheses, 162–163
monolayer culture, 56, 57f, 60, 193
MOP designs, 164
motion segment, 192
mouse, 40, 42t,71
MRI
annulus disruption, 23, 23f
black disc, 32
classification, 21, 22f
discal cyst, 26, 26f
disc herniation, 21f,23–26, 24–25f
endplate changes, 26, 27–29f
historical perspective, 20, 20f
image acquisition, 20–21, 21–22f
intradural disc herniations, 24f,26
pathoanatomy, 21
quantification, 20f,22–23
terminology, 192
multipotent stem cells, 55, 111t, 193, 194
Nachemson, A., 30, 48
National Institutes of Health (NIH), 195
NeoCart, 83t, 84, 85t
neutral zone, 192
Nose2Knee, 83t, 84, 85t
notochordal cells
animal models of, 43, 43t
defined, 192
human, 3, 14
as regeneration source, 55
Novocart, 83t,84
Novocart 3D, 83t, 84, 85t
nucleus pulposus
anatomy, 6, 7f,9f,13f
autografting, 150–152, 151–153f
biological replacements, 61
biologics therapy, 77–79, 82, 87
biomechanics, 30–31, 31f
defined, 192
disc regeneration, 54
grading, 49, 50–51t
hydrogel culture systems, 57f, 58, 60
monolayer culture, 56, 57f, 60, 193
organ culture, 59, 59f,69f,70
pH and, 60
phenotypic markers, 115–116
progenitor cells, 55, 115, 193
stem cell therapy, 113, 114
three-dimensional culture, 56, 57f, 66, 72, 72f
Olmarker, K., 145
one-piece prostheses, 160–161, 163–164t
OP-1, 102t, 103–104, 134t, 135. see also BMP 7
open innovation models, 177, 180, 196
organ culture
advantages, disadvantages, 66t,71
annulus fibrosis damage, repair, 69–70, 69f
bioreactor systems, 67–69, 68f, 71, 193, 194
cartilage end plate, repair, 70
defined, 193
disc regeneration, 59, 59f
history of, 67–69, 68f
MSCs, 55, 57f, 60, 67, 70–71
new therapy testing, 71–72, 72f
nucleus pulposus damage, repair, 768f,70
overview, 66–67
terminology, 194
transpedicular surgical approach, 69, 69f
organs-on-chip, 72
Index
, 194
201
Index
Orozco, L., 126, 142t
Orphan Drug Status, 174, 196
osteotomy, 195
Osti, O. L., 185
paeoniflorin, 92t,95
Panjabi, M. M., 30, 34
PCL, 132t, 133
PCM, 163t, 166–167
PDLLA/45S5 bioglass, 132t, 133
pellet culture, 56–58, 193
Peniel 2000, 92t, 94, 95f
pentosan polysaccharide (PPS), 185
Pettine, K. A ., 143t
Pfirrmann, C. W. A., 48, 52
Pfirrmann grading, 21, 22f
Phase I/II/III clinical research, 172–173, 196
phospholipase A2, 178
pig, 39, 41–42f,42t
platelet-rich fibrin (PRF), 85
platelet-rich plasma (PRP). see also growth factor injection
in annulus fibrosis repair, 134t, 135
auricular cartilage repair, 85
clinical trials, 144
HCT/Ps regulation, 170–171, 180
injection treatment effects, 101–103t, 105
IVD degeneration, 79
in organ culture, 70
overview, 101
pluripotent stem cells, 55, 111t, 112, 113t, 193, 194
Pope, M. H., 30
posterior longitudinal ligament (PLL), 24
Postmarketing Commitments (PMCs), 173, 196
Postmarketing Requirements (PMRs), 173, 196
press-fit insertion, 195
Prestige ST/LP, 163, 163t
primary germ layers, 194
primate, non-human, 41–42f,42t, 45, 150, 151
ProDisc, 161
ProDisc-C, 163–164t
progenitor/precursor stem cells, 111t, 112f, 115, 146–147,
185, 194
prophylactics, 80
prostheses. see also total disc arthroplasty
dual-bearing, 161–162, 161f, 163–164t
fixed-bearing, 161, 163–164t
MOM, 162–
one-piece, 160–161, 163–164t
proteoglycans, 5–7, 12, 14
PTMC-PU, 132t, 133
Public Health Service Act (PHSA) of 1944, 170
Purcell, M. H., 186
Pure Food and Drugs Act of 1906, 170
PushLock, 129, 130f, 130t
quadrupedal, 195
163
rabbit, 39, 41f,42–43t, 71, 80
radiological instability, 192
radiology grading scales, 50–52, 52t, 111f
range of motion, 193
rat, 39, 41f,42t,71
regulatory framework
accountability, 175
biological products, 171
Biologics License Application (BLA), 174
cell-based therapies, 174
clinical trials, 172–173, 173t
commercialization, 175
exemptions, 171
FDA, 174–175, 174t, 196
HCT/Ps, 170–171, 180, 196
Investigational New Drug Application process, 171,
171–172t, 195
manufacturing, 175
overview, 170
postmarketing, 173, 196
preclinical, clinical testing, 175
Quality Management System, 175
team, 175
terminology, 195–196
research areas
animal models, 184–185
annular integrity restoration, 186
arthritic changes, 186
cell-based therapies, 187
cells, matrix, pain-related molecules, 184, 187
genetic markers, 184
lncRNA, miRNA, 187
lumbar disc surgery, 186
MPCs, 185
multifactoriality, 186
pathophysiology, 185–186
regulatory challenges, 186, 187
tissue engineering, 186–187
resveratol, 92–93t,95–96
RevaFlex, 83t, 84, 85t
Rhesus monkeys, 150, 151
rheumatoid arthritis, 79
rhGDF-5, 97t, 101–104t, 103–104, 104f, 116, 141t
Roberts, S., 67
Rutges, J. P., 49, 51t
Sakai, D., 115
Sato, M., 116
scaffold systems, 57f, 58, 70, 81, 82, 116, 193
Schek, R. M., 70
Schmorl, Georg, 30
Schneiderman, G., 50–52
sciatica, 145
Secure C, 163t
SEMAC, 192
202
Index
sheep, 39, 41–42f,42–43t
silk, 131f, 132t
simvastatin, 93t, 103t, 134t, 135
sinuvertebral nerve, 6f
small leucine rich protein (SLRP) family, 5–6
somatic cell, 194
SOX9, 97t, 99, 115
sponsor, 196
SPORT trial, 20
statins, 92–93t, 93, 103t, 134t, 135
Steck, E., 116
stem cells. see also cell-based therapies
adipose-derived stem cells (ADSCs), 114, 116, 117,
134t
adult, 194
adult muscle tissue as source, 114–115
bone marrow stem cell (BMSC), 111t, 114, 141t, 194
clinical trials, 113–114 t
embryonic stem cells (ESCs), 55, 111t, 113, 193, 194
HCT/Ps regulation, 170–171, 180
hematopoietic stem cells (HSCs), 111t, 141t, 146, 194
induced pluripotent stem cells (iPSCs), 55, 113–114,
193
multipotent, 55, 111t, 193, 194
pluripotent, 55, 111t, 112, 113t, 193, 194
potency, 194
progenitor/precursor, 111t, 112f, 115, 146–147, 194
regulation of, 170
terminology, 194–195
totipotent, 112t, 195
Stoyanov, J. V., 116
Strassburg, S., 71
structural failure, 193
subligamentous herniation, 24, 24f
subluxation, 195
substance P receptor antagonist, 134t, 135
supraligamentous herniation, 24, 25f
T-cell lymphomas, 145
technologies
development of, 177–178
health care economics, 180
intellectual property, 179, 196
intervention, targets for, 178
minimally invasive procedures, 178
open innovation models, 177, 180, 196
pathophysiology, 178
regulatory pathway, 179–180 (see also regulatory
framework)
translational research, 179
TFG-β, 101t
TGF-β1, 97–98t,98
Thompson, J. P., 48, 101
Thompson grading system, 13t,48–49, 49t
three-dimensional culture, 56, 57f, 66, 72, 72f, 194
3R, 194
TIMP-1, 98, 98t
TIMP-3, 115
tissue engineered IVD (TE-IVD), 87, 147–148. see also bio-
logics
tissue engineering, 186–187
tissue implantation, 141f, 141t, 147–148
tissue inhibitors of matrix metalloproteinase (TIMP), 14
T2 mapping, 192
total disc arthroplasty
adjacent segment disease, 167
complications, 167–168
contraindications, 165–166
coupled motion, 158, 159, 159–160f
designs, current, 164–165
dual-bearing prostheses, 161– 162, 161f, 163–164t
fixed-bearing prostheses, 161, 163–164t
hard-on-hard bearings, 162–163
hard-on-soft bearings, 163– 164
hybrid designs, 162
indications, 165
one-piece prostheses, 160–161, 163–164t
outcomes, 158, 166–167
overview, 158–159, 168
patient selection, 165–166
revision procedures, 167
total disc transplantation
allograft biology, 154, 155f
animal models of, 150–152
autografting, 150–152, 151–153f
clinical applications, 155– 156
clinical trials, 148, 150–152, 152f
cryopreservation protocols, 152–153, 153f, 195
disc regeneration, 59, 61, 155
graft posit ioning, 154
history of, 150
sterilization, 153–154
surgical technique, goat, 154–155, 156f
terminology, 195
totipotent stem cells, 112t, 195
traction osteophyte, 195
translational research, 179
T1-rho, 192
Triple Aim, 180, 196
Tuakli-Wosornu, Y. A., 143t
21st Century Cures Act of 2016, 174
ultrashort time-to-echo (UTE), 20, 192
Urban, J. P., 67
Vadalà, G., 69, 114
Valley of Death, 179, 196
vascular network anatomy, 5f
vertebral column anatomy, 2, 2f
vertebral end plate
anatomy, 6–8, 7f
cartilage cells, 4
203
Index
changes, MRI, 26, 27–28f
defined, 192
grading, 49, 50–51t
monolayer culture, 56, 57f, 60, 193
organ culture, 70
Walsh, A. J., 103
Walter, B. A., 68–69
White, A. A., 34
White, P. J., 186
whole organ culture, 194. see also organ culture
Wuertz, K., 115
Xclose, 129, 130f, 130t
Yamamoto, Y., 114
Yoshikawa, T., 114, 142t, 146
Zhao, F., 33
204