Die Regenerative Medizin ist ein relativ neues Gebiet der
Biomedizin, deren Name dem lateinischen Wort regeneratio entstammt und
Neuentstehung bedeutet. Sie befasst sich mit der Anregung endogener
Regenerations- und Reparaturprozesse zur körpereigenen Wiederherstellung
funktionsgestörter Zellen, Gewebe und Organe und, wenn die eigenen
Reparaturmechanismen versagen, mit dem biologischen Ersatz dieser Strukturen.
Im Fachgebiet der Orthopädie und Unfallchirurgie kommt den Erkrankungen
und Verletzungen des muskuloskelettalen Systems eine große Bedeutung zu.
Besonders degenerative Erkrankungen der großen Gelenke und der
Wirbelsäule, aber auch traumatische, entzündliche, tumor- oder
operationsbedingte Weichteil- oder Knochendefekte sind Gegenstand der Forschung
in der Regenerativen Medizin. Vor allem der hyaline Gelenkknorpel, der
Bandscheibenknorpel und der Knochen werden in der Regenerativen Medizin als
klinisch relevante und wissenschaftlich zukunftsorientierte Strukturen
betrachtet. Wichtige Forschungsgebiete umfassen Strategien der
In-situ-Regeneration, das Tissue Engineering, die Stammzelldifferenzierung und
auch die Gentherapie.
Literatur
- 1
Kuettner K E, Aydelotte M B, Thonar E J.
Articular cartilage matrix and structure: a minireview.
J Rheumatol.
1991;
27 (Suppl.)
46-48
- 2
Jadin K D. et al .
Depth-varying density and organization of chondrocytes in
immature and mature bovine articular cartilage assessed by 3d imaging and
analysis.
J Histochem Cytochem.
2005;
53
1109-1119
- 3
Aydelotte M B, Kuettner K E.
Differences between sub-populations of cultured bovine
articular chondrocytes. I. Morphology and cartilage matrix production.
Connect Tissue Res.
1988;
18
205-222
- 4
Venn M, Maroudas A.
Chemical composition and swelling of normal and
osteoarthrotic femoral head cartilage. I. Chemical composition.
Ann Rheum Dis.
1977;
36
121-129
- 5
Nieminen M T. et al .
T2 relaxation reveals spatial collagen architecture in
articular cartilage: a comparative quantitative MRI and polarized light
microscopic study.
Magn Reson Med.
2001;
46
487-493
- 6
Maroudas A, Venn M.
Chemical composition and swelling of normal and
osteoarthrotic femoral head cartilage. II. Swelling.
Ann Rheum Dis.
1977;
36
399-406
- 7
Burr D B.
Anatomy and physiology of the mineralized tissues: role in
the pathogenesis of osteoarthrosis.
Osteoarthritis Cartilage.
2004;
12 (Suppl. A)
S20-S30
- 8
Mow V C, Holmes M H, Lai W M.
Fluid transport and mechanical properties of articular
cartilage: a review.
J Biomech.
1984;
17
377-394
- 9
Chen A C. et al .
Depth- and strain-dependent mechanical and electromechanical
properties of full-thickness bovine articular cartilage in confined
compression.
J Biomech.
2001;
34
1-12
- 10
Krishnan R. et al .
Inhomogeneous cartilage properties enhance superficial
interstitial fluid support and frictional properties, but do not provide a
homogeneous state of stress.
J Biomech Eng.
2003;
125
569-577
- 11
Schinagl R M. et al .
Depth-dependent confined compression modulus of
full-thickness bovine articular cartilage.
J Orthop Res.
1997;
15
499-506
- 12
Klein T J. et al .
Depth-dependent biomechanical and biochemical properties of
fetal, newborn, and tissue-engineered articular cartilage.
J Biomech.
2007;
40
182-190
- 13
Hunziker E B, Quinn T M, Hauselmann H J.
Quantitative structural organization of normal adult human
articular cartilage.
Osteoarthritis Cartilage.
2002;
10
564-572
- 14
Poole C A.
Articular cartilage chondrons: form, function and
failure.
J Anat.
1997;
191
1-13
- 15
Lu X L, Mow V C.
Biomechanics of articular cartilage and determination of
material properties.
Med Sci Sports Exerc.
2008;
40
193-199
- 16
Lu X L. et al .
The generalized triphasic correspondence principle for
simultaneous determination of the mechanical properties and proteoglycan
content of articular cartilage by indentation.
J Biomech.
2007;
40
2434-2441
- 17
Buschmann M D, Grodzinsky A J.
A molecular model of proteoglycan-associated electrostatic
forces in cartilage mechanics.
J Biomech Eng.
1995;
117
179-192
- 18 Meachim G, Stockwell R.
The matrix. In: Freeman MAR, ed Adult Articular Cartilage. Tunbridge Wells; Pitman Medical 1979:
1-67
- 19
Jay G D. et al .
Homology of lubricin and superficial zone protein (SZP):
products of megakaryocyte stimulating factor (MSF) gene expression by human
synovial fibroblasts and articular chondrocytes localized to chromosome
1q25.
J Orthop Res.
2001;
19
677-687
- 20
Schumacher B L. et al .
A novel proteoglycan synthesized and secreted by chondrocytes
of the superficial zone of articular cartilage.
Arch Biochem Biophys.
1994;
311
144-152
- 21
Lee D A. et al .
Response of chondrocyte subpopulations cultured within
unloaded and loaded agarose.
J Orthop Res.
1998;
16
726-733
- 22
Tallheden T. et al .
Human articular chondrocytes – plasticity and
differentiation potential.
Cells Tissues Organs.
2006;
184
55-67
- 23
Bywaters E.
The metabolism of joint tissues.
J Path Bact.
1937;
44
247-268
- 24
Quinn T M, Hunziker E B, Hauselmann H J.
Variation of cell and matrix morphologies in articular
cartilage among locations in the adult human knee.
Osteoarthritis Cartilage.
2005;
13
672-678
- 25
Stockwell R A.
The interrelationship of cell density and cartilage thickness
in mammalian articular cartilage.
J Anat.
1971;
109
411-421
- 26
Kim A C, Spector M.
Distribution of chondrocytes containing alpha-smooth muscle
actin in human articular cartilage.
J Orthop Res.
2000;
18
749-755
- 27
Jurvelin J S. et al .
Surface and subsurface morphology of bovine humeral articular
cartilage as assessed by atomic force and transmission electron
microscopy.
J Struct Biol.
1996;
117
45-54
- 28
Darling E M, Hu J C, Athanasiou K A.
Zonal and topographical differences in articular cartilage
gene expression.
J Orthop Res.
2004;
22
1182-1187
- 29
Khan I M. et al .
Expression of clusterin in the superficial zone of bovine
articular cartilage.
Arthritis Rheum.
2001;
44
1795-1799
- 30
Eger W. et al .
Human knee and ankle cartilage explants: catabolic
differences.
J Orthop Res.
2002;
20
526-534
- 31
Brighton C T, Kitajima T, Hunt R M.
Zonal analysis of cytoplasmic components of articular
cartilage chondrocytes.
Arthritis Rheum.
1984;
27
1290-1299
- 32
Rolauffs B. et al .
Distinct horizontal patterns in the spatial organization of
superficial zone chondrocytes of human joints.
J Struct Biol.
2008;
162
335-344
- 33 Maroudas A.
Physico-chemical properties of articular cartilage. In: Freeman MAR, ed Adult Articular Cartilage. Tunbridge Wells; Pitman Medical 1979:
215-290
- 34 Hunziker E B.
Articular cartilage structure in humans and experimental
animals. In: Kuettner KE, Schleyerbach R, Peyron JG, Hascall VC,
eds Articular Cartilage and Osteoarthritis. New York; Raven Press 1992: 183-199
- 35
Repo R U, Finlay J B.
Survival of articular cartilage after controlled impact.
J Bone Joint Surg Am.
1977;
59
1068-1076
- 36
Jeffrey J E, Gregory D W, Aspden R M.
Matrix damage and chondrocyte viability following a single
impact load on articular cartilage.
Arch Biochem Biophys.
1995;
322
87-96
- 37
Torzilli P A. et al .
Effect of impact load on articular cartilage: cell metabolism
and viability, and matrix water content.
J Biomech Eng.
1999;
121
433-441
- 38
Ewers B J. et al .
The extent of matrix damage and chondrocyte death in
mechanically traumatized articular cartilage explants depends on rate of
loading.
J Orthop Res.
2001;
19
779-784
- 39
Kerin A J. et al .
Propagation of surface fissures in articular cartilage in
response to cyclic loading in vitro.
Clin Biomech (Bristol, Avon).
2003;
18
960-968
- 40
Chen C T. et al .
Time, stress, and location dependent chondrocyte death and
collagen damage in cyclically loaded articular cartilage.
J Orthop Res.
2003;
21
888-898
- 41
Kurz B. et al .
Biosynthetic response and mechanical properties of articular
cartilage after injurious compression.
J Orthop Res.
2001;
19
1140-1146
- 42
Kurz B. et al .
Pathomechanisms of cartilage destruction by mechanical
injury.
Ann Anat.
2005;
187
473-485
- 43
Curl W W. et al .
Cartilage injuries: a review of 31,516 knee
arthroscopies.
Arthroscopy.
1997;
13
456-460
- 44
Alford J W, Cole B J.
Cartilage restoration, part 1: basic science, historical
perspective, patient evaluation, and treatment options.
Am J Sports Med.
2005;
33
295-306
- 45
Oeppen R S. et al .
Acute injury of the articular cartilage and subchondral bone:
a common but unrecognized lesion in the immature knee.
AJR Am J Roentgenol.
2004;
182
111-117
- 46
Hunter W.
Of the structure and disease of articulating cartilages.
1743.
Clin Orthop Relat Res.
1995;
317
3-6
- 47
Furukawa T. et al .
Biochemical studies on repair cartilage resurfacing
experimental defects in the rabbit knee.
J Bone Joint Surg Am.
1980;
62
79-89
- 48
Nehrer S, Spector M, Minas T.
Histologic analysis of tissue after failed cartilage repair
procedures.
Clin Orthop Relat Res.
1999;
365
149-162
- 49
Davis M A. et al .
The association of knee injury and obesity with unilateral
and bilateral osteoarthritis of the knee.
Am J Epidemiol.
1989;
130
278-288
- 50
Baumgaertner M R. et al .
Arthroscopic debridement of the arthritic knee.
Clin Orthop Relat Res.
1990;
253
197-202
- 51
Hubbard M J.
Articular debridement versus washout for degeneration of the
medial femoral condyle. A five-year study.
J Bone Joint Surg Br.
1996;
78
217-219
- 52
Moseley J B. et al .
A controlled trial of arthroscopic surgery for osteoarthritis
of the knee.
N Engl J Med.
2002;
347
81-88
- 53
Insall J N.
Intra-articular surgery for degenerative arthritis of the
knee. A report of the work of the late K. H. Pridie.
J Bone Joint Surg Br.
1967;
49
211-228
- 54
Mitchell N, Shepard N.
The resurfacing of adult rabbit articular cartilage by
multiple perforations through the subchondral bone.
J Bone Joint Surg Am.
1976;
58
230-233
- 55
Johnson L L.
Arthroscopic abrasion arthroplasty historical and pathologic
perspective: present status.
Arthroscopy.
1986;
2
54-69
- 56
Steadman J R. et al .
[The microfracture technic in the management of complete
cartilage defects in the knee joint].
Orthopäde.
1999;
28
26-32
- 57
Rudd R G. et al .
The effects of beveling the margins of articular cartilage
defects in immature dogs.
Vet Surg.
1987;
16
378-383
- 58
Alford J W, Cole B J.
Cartilage restoration, part 2: techniques, outcomes, and
future directions.
Am J Sports Med.
2005;
33
443-460
- 59
Steadman J R. et al .
Outcomes of microfracture for traumatic chondral defects of
the knee: average 11-year follow-up.
Arthroscopy.
2003;
19
477-484
- 60
Frisbie D D. et al .
Arthroscopic subchondral bone plate microfracture technique
augments healing of large chondral defects in the radial carpal bone and medial
femoral condyle of horses.
Vet Surg.
1999;
28
242-255
- 61
Frisbie D D. et al .
Effects of calcified cartilage on healing of chondral defects
treated with microfracture in horses.
Am J Sports Med.
2006;
34
1824-1831
- 62
Steadman J R, Rodkey W G, Rodrigo J J.
Microfracture: surgical technique and rehabilitation to treat
chondral defects.
Clin Orthop Relat Res.
2001;
391 (Suppl)
S362-369
- 63
Buckwalter J A, Mow V C, Ratcliffe A.
Restoration of Injured or Degenerated Articular
Cartilage.
J Am Acad Orthop Surg.
1994;
2
192-201
- 64
Yamashita F. et al .
The transplantation of an autogeneic osteochondral fragment
for osteochondritis dissecans of the knee.
Clin Orthop Relat Res.
1985;
201
43-50
- 65
Matsusue Y, Yamamuro T, Hama A.
Arthroscopic multiple osteochondral transplantation to the
chondral defect in the knee associated with anterior cruciate ligament
disruption.
Arthroscopy.
1993;
9
318-321
- 66
Cain E L, Clancy W G.
Treatment algorithm for osteochondral injuries of the
knee.
Clin Sports Med.
2001;
20
321-342
- 67
Pearce S G. et al .
An investigation of 2 techniques for optimizing joint surface
congruency using multiple cylindrical osteochondral autografts.
Arthroscopy.
2001;
17
50-55
- 68
Bartz R L. et al .
Topographic matching of selected donor and recipient sites
for osteochondral autografting of the articular surface of the femoral
condyles.
Am J Sports Med.
2001;
29
207-212
- 69
Hunziker E B, Quinn T M.
Surgical removal of articular cartilage leads to loss of
chondrocytes from cartilage bordering the wound edge.
J Bone Joint Surg Am.
2003;
85 (Suppl. 2)
85-92
- 70
Hangody L, Fules P.
Autologous osteochondral mosaicplasty for the treatment of
full-thickness defects of weight-bearing joints: ten years of experimental and
clinical experience.
J Bone Joint Surg Am.
2003;
85 (Suppl. 2)
25-32
- 71
Shasha N. et al .
Long-term follow-up of fresh tibial osteochondral allografts
for failed tibial plateau fractures.
J Bone Joint Surg Am.
2003;
85 (Suppl. 2)
33-39
- 72
Williams R J 3rd, Dreese J C, Chen C T.
Chondrocyte survival and material properties of
hypothermically stored cartilage: an evaluation of tissue used for
osteochondral allograft transplantation.
Am J Sports Med.
2004;
32
132-139
- 73
Williams S K. et al .
Prolonged storage effects on the articular cartilage of fresh
human osteochondral allografts.
J Bone Joint Surg Am.
2003;
85
2111-2120
- 74
Ochs B G. et al .
[Treatment of osteochondritis dissecans of the knee:
one-step procedure with bone grafting and matrix-supported autologous
chondrocyte transplantation].
Z Orthop Unfall.
2007;
145
146-151
- 75
Brittberg M. et al .
Treatment of deep cartilage defects in the knee with
autologous chondrocyte transplantation.
N Engl J Med.
1994;
331
889-895
- 76
Schnabel M. et al .
Dedifferentiation-associated changes in morphology and gene
expression in primary human articular chondrocytes in cell culture.
Osteoarthritis Cartilage.
2002;
10
62-70
- 77
Domm C. et al .
Redifferentiation of dedifferentiated bovine articular
chondrocytes in alginate culture under low oxygen tension.
Osteoarthritis Cartilage.
2002;
10
13-22
- 78
Ochi M. et al .
Transplantation of cartilage-like tissue made by tissue
engineering in the treatment of cartilage defects of the knee.
J Bone Joint Surg Br.
2002;
84
571-578
- 79
Stoop R.
Smart biomaterials for tissue engineering of cartilage.
Injury.
2008;
39 (Suppl. 1)
S77-87
- 80
Koay E J, Athanasiou K A.
Hypoxic chondrogenic differentiation of human embryonic stem
cells enhances cartilage protein synthesis and biomechanical
functionality.
Osteoarthritis Cartilage.
2008;
16
1450-1456
- 81
Kisiday J D. et al .
Effects of dynamic compressive loading on chondrocyte
biosynthesis in self-assembling peptide scaffolds.
J Biomech.
2004;
37
595-604
- 82
Vinatier C. et al .
Cartilage engineering: a crucial combination of cells,
biomaterials and biofactors.
Trends Biotechnol.
2009;
27
307-314
- 83
Bentley G. et al .
A prospective, randomised comparison of autologous
chondrocyte implantation versus mosaicplasty for osteochondral defects in the
knee.
J Bone Joint Surg Br.
2003;
85
223-230
- 84
LaPrade R F. et al .
Histologic and immunohistochemical characteristics of failed
articular cartilage resurfacing procedures for osteochondritis of the knee:
a
case series.
Am J Sports Med.
2008;
36
360-368
- 85
Saris D B. et al .
Characterized chondrocyte implantation results in better
structural repair when treating symptomatic cartilage defects of the knee in
a
randomized controlled trial versus microfracture.
Am J Sports Med.
2008;
36
235-246
- 86
Richter W.
Cell-based cartilage repair: illusion or solution for
osteoarthritis.
Curr Opin Rheumatol.
2007;
19
451-456
- 87
Breinan H A. et al .
Healing of canine articular cartilage defects treated with
microfracture, a type-II collagen matrix, or cultured autologous
chondrocytes.
J Orthop Res.
2000;
18
781-789
- 88
Brittberg M.
Autologous chondrocyte implantation–technique and
long-term follow-up.
Injury.
2008;
39 (Suppl. 1)
S40-49
- 89
Knutsen G. et al .
Autologous chondrocyte implantation compared with
microfracture in the knee. A randomized trial.
J Bone Joint Surg Am.
2004;
86
455-464
- 90
Knutsen G. et al .
A randomized trial comparing autologous chondrocyte
implantation with microfracture. Findings at five years.
J Bone Joint Surg Am.
2007;
89
2105-2112
- 91
Han E. et al .
Shaped, stratified, scaffold-free grafts for articular
cartilage defects.
Clin Orthop Relat Res.
2008;
466
1912-1920
- 92
Tallheden T. et al .
Proliferation and differentiation potential of chondrocytes
from osteoarthritic patients.
Arthritis Res Ther.
2005;
7
R560-R568
- 93
Corsi K A. et al .
Regenerative medicine in orthopaedic surgery.
J Orthop Res.
2007;
25
1261-1268
- 94
Conrad S. et al .
Generation of pluripotent stem cells from adult human
testis.
Nature.
2008;
456
344-349
- 95
Dominici M. et al .
Minimal criteria for defining multipotent mesenchymal stromal
cells. The International Society for Cellular Therapy position statement.
Cytotherapy.
2006;
8
315-317
- 96
Canalis E, Economides A N, Gazzerro E.
Bone morphogenetic proteins, their antagonists, and the
skeleton.
Endocr Rev.
2003;
24
218-235
- 97
Grimaud E, Heymann D, Redini F.
Recent advances in TGF-beta effects on chondrocyte
metabolism. Potential therapeutic roles of TGF-beta in cartilage
disorders.
Cytokine Growth Factor Rev.
2002;
13
241-257
- 98
Fan H. et al .
Porous gelatin-chondroitin-hyaluronate tri-copolymer scaffold
containing microspheres loaded with TGF-beta1 induces differentiation of
mesenchymal stem cells in vivo for enhancing cartilage repair.
J Biomed Mater Res A.
2006;
77
785-794
- 99
Blaney Davidson E N, van der Kraan P M, van den Berg W B.
TGF-beta and osteoarthritis.
Osteoarthritis Cartilage.
2007;
15
597-604
- 100
Sekiya I. et al .
Comparison of effect of BMP-2, -4, and -6 on in vitro
cartilage formation of human adult stem cells from bone marrow stroma.
Cell Tissue Res.
2005;
320
269-276
- 101
Grunder T. et al .
Bone morphogenetic protein (BMP)-2 enhances the expression of
type II collagen and aggrecan in chondrocytes embedded in alginate beads.
Osteoarthritis Cartilage.
2004;
12
559-567
- 102
Kuo A C. et al .
Microfracture and bone morphogenetic protein 7 (BMP-7)
synergistically stimulate articular cartilage repair.
Osteoarthritis Cartilage.
2006;
14
1126-1135
- 103
Goldring M B, Tsuchimochi K, Ijiri K.
The control of chondrogenesis.
J Cell Biochem.
2006;
97
33-44
- 104
Garrison K R. et al .
Clinical effectiveness and cost-effectiveness of bone
morphogenetic proteins in the non-healing of fractures and spinal fusion: a
systematic review.
Health Technol Assess.
2007;
11
1-150, iii – iv
- 105
Stewart A A. et al .
Effect of fibroblast growth factor-2 on equine mesenchymal
stem cell monolayer expansion and chondrogenesis.
Am J Vet Res.
2007;
68
941-945
- 106
Ellman M B. et al .
Biological impact of the fibroblast growth factor family on
articular cartilage and intervertebral disc homeostasis.
Gene.
2008;
420
82-89
- 107
Davies L C. et al .
The potential of IGF-1 and TGFbeta1 for promoting
”adult” articular cartilage repair: an in vitro study.
Tissue Eng Part A.
2008;
14
1251-1261
- 108
Uebersax L, Merkle H P, Meinel L.
Insulin-like growth factor I releasing silk fibroin scaffolds
induce chondrogenic differentiation of human mesenchymal stem cells.
J Control Release.
2008;
127
12-21
- 109
Schett G.
How does joint remodeling work? New insights in the molecular
regulation of the architecture of joints.
Cell Adh Migr.
2007;
1
102-103
- 110
Edwards P C. et al .
Sonic hedgehog gene-enhanced tissue engineering for bone
regeneration.
Gene Ther.
2005;
12
75-86
- 111
Richardson S M, Hoyland J A.
Stem cell regeneration of degenerated intervertebral discs:
current status.
Curr Pain Headache Rep.
2008;
12
83-88
- 112
Evans C H, Ghivizzani S C, Robbins P D.
Orthopedic gene therapy in 2008.
Mol Ther.
2009;
17
231-244
Dr. med. Bernd Rolauffs
Berufsgenossenschaftliche Unfallklinik Tübingen
Schnarrenbergstr. 95
72076 Tübingen
Phone: 07071/253815
Email: berndrolauffs@googlemail.com
