Zusammenfassung
Tissue engineering eröffnet neue Möglichkeiten für die Meniskusheilung und den Meniskusersatz. Auf diesem Gebiet werden verschiedene Ansätze verfolgt, um ein Implantat für den Meniskusersatz durch die Kombination aus einem Matrixgerüst, Zellen und spezifischen Stimuli zu generieren. Meniskusersatz durch azelluläre Matrizes: Eine Matrix für den Meniskusersatz muss hohen biomechanischen Ansprüchen gerecht werden. Hierbei stellen neben der Implantatgeometrie die Materialeigenschaften und eine sichere intraartikuläre Fixation die Voraussetzung für die Implantatfunktion dar. Ein azelluläres Kollagen-Gerüst wird als partieller Meniskusersatz bereits klinisch eingesetzt. Außerdem sind resorbierbare Polymere sowie ein Implantat aus Dünndarmsubmukosa im Tierversuch erprobt worden. Nach Implantation werden diese Matrizes von Zellen besiedelt und unterliegen einem Remodeling. Die Bildung eines fibrokartilaginären Regeneratgewebes wurde beobachtet. Die biomechanische Qualität von Implantaten und deren Auswirkungen auf den Knorpelschutz müssen noch weiter untersucht werden. Zelluläre Besiedelung von Matrizes für den Meniskusersatz: Eine zelluläre Besiedelung von Matrizes in vitro könnte zu einer Verbesserung der biologischen und biomechanischen Implantateigenschaften führen. Allerdings ist der hierfür ideale Zelltyp noch nicht definiert. Autologe Meniskuszellen, artikuläre Chondrozyten und mesenchymale Stammzellen stellen mögliche zelluläre Quellen dar. Zusätzliche Stimuli, wie Zytokine und mechanische Kräfte, sowie gentechnische Verfahren bieten Möglichkeiten, die Qualität eines Ersatzgewebes weiter zu steigern.
Abstract
Tissue engineering offers new opportunities for meniscus repair and replacement. In this field different approaches are being studied to genererate a meniscus subsitute by a combination of a matrix scaffold, cells and specific stimuli. Meniscus replacement by acelluar matrices: For meniscus replacement the matrix material has to meet high biomechanical demands. Besides implant geometry, the material properties and a secure intraarticular attachment are important preconditions for implant function. A collagen scaffold has already been applied clinically for partial meniscus replacement. Scaffolds made of synthetic, bioabsorbable polymers and small intestine submucosa have been employed in animal studies. Following implantation, matrices are invaded by cells and undergo a process of remodeling. Formation of fibrocartilage repair tissue has been observerd. The biomechanical quality of implants and their effect on cartilage preservation have to be studied further. Cellular seeding of matrices for mensicus replacement: Advanced biological and biomechanical implant quality might be achieved by seeding matrices with cells in vitro. However, the ideal type of cell for this purpose has not yet been identified. Autologous mensicus cells, articular chondrocytes and mesenchymal stem cells represent possible cellular sources. Additional stimuli, such as cytokines and mechanical forces, and techniques of genetic engineering might further contribute to enhance the quality of engineered tissue.
Schlüsselwörter
Meniskus - Tissue engineering - Meniskusersatz - Matrix - Zelle
Key words
Meniscus - tissue engineering - meniscus replacement - matrix scaffold - cell
Literatur
-
1
Shoemaker S C, Markolf K L.
The role of the meniscus in the anterior-posterior stability of the loaded anterior cruciate deficient knee: effects of partial versus total excision.
J Bone Joint Surg [Am].
1986;
26
71-79
-
2
Hoshino A, Wallace W A.
Impact-absorbing properties of the human knee.
J Bone Joint Surg [Br].
1987;
69
807-811
-
3
Fukuda Y, Takai S, Yoshino N, Murase K, Tsutsumi S, Ikeuchi K, Hirasawa Y.
Impact load transmission of the knee joint-influence of leg alignment and the role of meniscus and articular cartilage.
Clin Biomech.
2000;
15
516-521
-
4
Wilson W, von Rietbergen B, van Donkelaar C C, Huiskes R.
Pathways of load-induced cartilage damage causing cartilage degeneration in the knee after meniscectomy.
Journal Biomech.
2003;
36
845-851
-
5
Elliott D M, Guilak F, Vail T P, Wang J Y, Setton L A.
Tensile properties of articular cartilage are altered by meniscectomy in a canine model of osteoarthritis.
J Orthop Res.
1999;
17
503-508
-
6
Wyland D J, Guilak F, Elliot D M, Setton L A, Vail T P.
Chondropathy after meniscal tear or partial meniscectomy in a canine model.
J Orthop Res.
2002;
20
996-1002
-
7
Cicuttini F M, Forbes A, Yunyuan W, Rush G, Stuckley S L.
Rate of knee cartilage loss after partial meniscectomy.
J Rheumatol.
2002;
39
1954-1956
-
8
Cox J S, Nye C E, Schaefer W W.
The degenerative effects of partial and total resection of the medial meniscus in the dogs knees.
Clin Orthop.
1975;
109
178-183
-
9
Allen P R, Denham R A, Swan A V.
Late degenerative changes after meniscectomy. Factors affecting the knee after operation.
J Bone Joint Surg [Br].
1984;
66
121-128
-
10
McCarty E C, Marx R G, DeHaven K E.
Meniscus Repair - Considerations in treatment and update of clinical result.
Clin Orthop.
2002;
402
122-134
-
11
Messner K.
The concept of a permanent synthetic meniscus prosthesis: a critical discussion after 5 years of experimental investigations using dacron and teflon implants.
Biomaterials.
1994;
15
243-250
-
12
Bruns J, Kahrs J, Kampen J, Behrens P, Plitz W.
Autologous perichondral tissue for meniscal replacement.
J Bone Joint Surg [Br].
1998;
80
918-923
-
13
Kohn D, Rudert M, Wirth C J, Plitz W, Reiss G, Maschek H.
Medial meniscus replacement by a fat pad autograft.
Int Orthop.
1997;
21
232-238
-
14
Kohn D, Wirth C J, Reiss G, Plitz W, Maschek H, Erhardt W, Wülker N.
Medial meniscus replacement by a tendon autograft. Experiments in sheep.
J Bone Joint Surg [Br].
1992;
74
910-917
-
15
Metak G, Scherer M A.
Development of replacement meniscus of autogenous tissue.
Unfallchirurg.
1996;
99
477-486
-
16
Johnson L L, Feagin J A.
Autogenous tendon graft substitution for absent knee joint meniscus: a pilot study.
Arthroscopy.
2000;
16
191-196
-
17
Goble E M, Kohn D, Verdonk R, Kane S M.
Meniscal substitutes - human experience.
Scand J Med Sci Sports.
1999;
9
146-157
-
18
Kohn D.
Autograft meniscus replacment: experimental and clinical results.
Knee Surg Sports Traumatol Arthrosc.
1993;
1
123-125
-
19
Milachowski K A, Kohn D, Wirth C J.
Meniscus replacement using Hoffa's infrapatellar fat body - initial clinical results.
Unfallchirurgie.
1990;
4
190-195
-
20
Verdonk R.
Meniscal transplantation.
Acta Orthop Belg.
2002;
68
118-127
-
21
Wirth C J, Peters G, Milachowski K A, Weismeier K G, Kohn D.
Long-term Results of Meniscal Allograft Transplantation.
Am J Sports Med.
2002;
2
174-181
-
22
Kohn D.
Meniskusersatz.
Orthopäde.
1994;
23
164-170
-
23
Jackson D W, McDevitt C A, Simon T M, Arnoczky S P, Atwell E A.
Meniscal transplantation using fresh and cryopreserved allografts. An experimental study in goats.
Am J Sports Med.
1992;
20
644-656
-
24
Arnoczky S P, DiCarlo E F, O'Brien S J, Warren R F.
Cellular repopulation of deep-frozen meniscsal autografts: An experimental study in the dog.
Arthroscopy.
1992;
8
428-436
-
25
Arnoczky S P, Warren R F, McDevitt C A.
Meniscal replacement using a cryopreserverd allograft.
Clin Orthop.
1990;
252
121-127
-
26
Shibuya S.
Meniscus transplantation using cryopreserved allograft. Histological and ultrastructural study of the transplanted meniscus.
J Orthop Sci.
1999;
4
135-141
-
27
Messner K, Kohn D, Verdonk R.
Future research in meniscal replacement.
Scand J Med Sci Sports.
1999;
9
181-183
-
28
Milachowski K A, Kohn D, Wirth C J.
Transplantation allogener Menisken.
Orthopäde.
1994;
23
160-163
-
29
Rodeo S A, Seneviratne A, Suzuki K, Wickiewicz T L, Warren R F.
Histological analysis of human meniscal allografts. A preliminary study.
J Bone Joint Surg [Am].
2000;
82
1071-1082
-
30
Hamlet W, Liu S H, Yang R.
Destruction of a cryopreserved meniscal allograft: a case for acute rejection.
Arthroscopy.
1997;
13
517-521
-
31
Lazovic D, Wirth C J, Sieg A, Gosse F, Maschek H G, Shaffer B.
Effect of surgical technique on meniscus transplants. A histological, animal experiment study.
Unfallchirurg.
1997;
100
541-546
-
32
Milachowski K A, Weismeier K, Wirth C J, Kohn D.
Meniscus transplantation and anterior cruciate ligament replacement - results 2-4 years postoperativ.
Sportverletz Sportschaden.
1990;
4
73-78
-
33
Stollsteimer G T, Shelton W R, Dukes A, Bomboy A L.
Meniscal allograft transplantation: A 1- to 5-year follow-up of 22 patients.
Arthroscopy.
2000;
16
343-347
-
34
Arnoczky S P.
Building a meniscus.
Clin Orthop.
1999;
367
244-253
-
35
Setton L A, Guilak F, Hsu E W, Vail T P.
Biomechanical factors in tissue engineered meniscal repair.
Clin Orthop.
1999;
367 (Suppl)
254-272
-
36
Middleton J C, Tipton A J.
Synthetic biodegradable polymers as orthopaedic devices.
Biomaterials.
2000;
21
2335-2346
-
37
Claes L, Ignatius A.
Development of new, biodegradable implants.
Chirurg.
2002;
73
990-996
-
38
De Groot J H, Zijlstra F M, Kuipers H W.
Meniscal tissue regeneration in porous 50/50 copoly (L-lacitde/espilon-caprolacotone) implants.
Biomaterials.
1997;
18
613-622
-
39
Buma P, Ramrattan N N, van Tienen T G, Veth R PH.
Tissue engineering of the meniscus.
Biomaterials.
2004;
25
1523-1532
-
40
Klompmaker J, Jansen H WB, Veth R PH, de Groot J H, Nijenhuis A J, Pennings A J.
Porous polymer implant for repair of meniscal lesions: A prelliminary study in dogs.
Biomaterials.
1991;
12
810-816
-
41
De Groot J H, de Vrijer R, Pennings A J, Klompmaker J, Veth R P, Jansen H W.
Use of porous polyurethanes for meniscal reconstruction and meniscal prostheses.
Biomaterials.
1996;
17
163-173
-
42
Tienen T G, Heijkants R G, Buma P, De Groot J H, Pennings A J, Veth R P.
A porous polymer scaffold for meniscal lesion repair - A study in dogs.
Biomaterials.
2003;
24
2541-2548
-
43
Klompmaker J, Veth R PH, Jansen H WB, Nielsen H KL, de Groot J H, Pennings A J.
Meniscal replacement using a porous polymer prosthesis: a preliminary study in the dog.
Biomaterials.
1996;
17
1169-1175
-
44
Kobayashi M, Toguchida J, Oka M.
Development of an artificial meniscus using polyvinyl alcohol-hydrogel for early return to, and continuance of athletic life, in sportspersons with severe meniscus injury. I: Mechanical evaluation.
Knee.
2003;
10
47-51
-
45
Kobayashi M, Toguchida J, Oka M.
Preliminary study of polyvinyl alcohol-hydrogel (PVA-H) artificial meniscus.
Biomaterials.
2003;
24
639-647
-
46
Testa Pezzin A P, Cardoso T P, do Carmo Alberto Rincon M, de Carvalho Zavaglia C A, de Rezende Duek E A.
Bioreabsorbable polymer scaffold as temporary meniscal prosthesis.
Artif Organs.
2003;
27
428-431
-
47
Cook J L, Tomlinson J L, Arnosczky S P, Fox D B, Cook C R, Kreeger J M.
Kinetic study of the replacment of porcine small intestinal submucosa grafts and the regeneration of meniscal-like tissue in large avascular meniscal defects in dogs.
Tissue engineering.
2001;
7
321-333
-
48
Gastel J A, Muirhead W R, Lifrak J T, Fadale P D, Hulstyn M J, Labrador D P.
Meniscal tissue regeneration using a collagenous biomaterial derived from porcine small intestine submucosa.
Arthroscopy.
2001;
17
151-159
-
49
Welch J A, Montgomery R D, Lenz S D, Plouhar P, Shelton W R.
Evaluation of small-intestinal submucosa implants for repair of meniscal defects in dogs.
Am J Vet Res.
2002;
63
427-431
-
50
Cook J L, Tomlinson J L, Kreeger J M, Cook C R.
Induction of meniscal regeneration in dogs using a novel biomaterial.
Am J Sports Med.
1999;
27
658-665
-
51
Stone K R.
Meniscus replacement.
Clin Sports Med.
1996;
15
557-571
-
52
Stone K R, Rodkey W G, Webber R, McKinney L, Steadman R J.
Meniscal regeneration with copolymeric collagen scaffolds. In vitro an in vivo studies evaluated clinically, histologically and biochemically.
Am J Sports Med.
1992;
20
104-111
-
53
Stone K R, Rodkey W G, Webber R J, McKinney L, Steadman R J.
Future directions. Collagen-based prosthesis for meniscal regeneration.
Clin Orthop.
1990;
252
129-135
-
54
Stone K R, Steadman J R, Rodkey W G, Li S T.
Regeneration of meniscal cartilage with use of a collagen scaffold. Analysis of preliminary data.
J Bone Joint Surg [Am].
1997;
79
1770-1777
-
55
Rodkey W G, Steadman J R, Li S T.
A clinical study of collagen meniscus implants to restore the injured meniscus.
Clin Orthop.
1999;
367 (Suppl)
281-292
-
56
Arnoczky S P, Warren R F, Spivak J M.
Menicsal repair using an exogenous fibrin clot. An experimental study in dogs.
J Bone Joint Surg [Am].
1988;
70
1209-1217
-
57
Hunziker E B.
Articular cartilage repair: Basic science and clinical progress. A review of the current status and prospects.
Osteoarthritis Cartilage.
2002;
10
432-463
-
58
Ghadially F N, Lalonde J M, Wedge J H.
Ultrastructure of normal and torn menisci of the human knee joint.
J Anat.
1983;
136
773-791
-
59
Nakata K, Shino K, Hamada M, Mae, T, Miyama T, Shinjo H, Horibe S, Tada K, Ochi T, Yoshikawa H.
Human meniscus cell - Characterization of the primary culture and use for tissue engineering.
Clin Orthop.
2001;
391
208-218
-
60
Webber R J, Harris M G, Hough A J.
Cell culture of rabbit meniscal fibrochondrocytes: Proliferative and synthetic response to growth factors and ascorbat.
J Orthop Res.
1985;
3
36-42
-
61
Webber R J.
In vitro culture of meniscal tissue.
Clin Orthop.
1990;
252
114-120
-
62
Webber R J, York J L, Vanderschilden J L, Hough A.
An organ culture model for assaying wound repair of the fibrocartilaginous knee joint meniscus.
Am J Sports Med.
1989;
17
393-400
-
63
Isoda K, Saito S.
In vitro and in vivo fibrochondrocyte growth behavior in fibrin gel.
Am J Knee Surg.
1998;
11
209-216
-
64
Tanaka T, Fujii K, Kumagae Y.
Comparison of biochemical characteristics of cultured fibrochondrocytes isolated from the inner and outer regions of human meniscus.
Knee Surg Sports Traumatol Arthosc.
1999;
7
75-80
-
65
Collier S, Gosh P.
Effects of transforming growth factor beta on proteoglycan synthesis by cell and explant cultures derived from the knee joint meniscus.
Osteoarthritis Cartilage.
1995;
3
127-138
-
66
Hidaka C, Ibarra C, Hannafin J A, Torzilli P A, Quitoriano M, Jen S S, Warren R F, Crystal R G.
Formation of vascularized meniscal tissue by combining gene therapy with tissue engineering.
Tissue Eng.
2002;
8
93-105
-
67
Bhargava M M, Attia E T, Murrell G A, Dolan M M, Warren R F, Hannafin J A.
The effect of cytokines on the proliferation and migration of bovine meniscal cells.
Am J Sports Med.
1999;
27
636-643
-
68
Zaleskas J M, Kinner B, Freyman T M, Yannas I V, Gibson L J, Spector M.
Growth factor regulation of smooth muscle actin expression and contraction of human articular chondrocytes and meniscal cells in collagen-GAG matrix.
Exp Cell Res.
2001;
270
21-31
-
69
Suzuki Y, Takeuchi N, Sagehashi Y, Yamaguchi T, Itoh H, Iwata H.
Effects of hyaluronic acid on meniscal injury in rabbits.
Arch Orthop Trauma Surg.
1998;
117
303-306
-
70
Ishima M, Wada Y, Sonoda M, Harada Y, Katsumi A, Moriya H.
Effects of hyaluronan on the healing of rabbit meniscus injured in the peripheral region.
J Orthop Sci.
2000;
5
579-584
-
71
Hashimoto J, Kurosaka M, Yoshiya S, Hirohata K.
Meniscal repair using fibrin sealant and endothelial cell growth factor.
Am J Sports Med.
1992;
20
537-541
-
72
Spindler K P, Mayes C E, Miller R R, Imro A K, Davidson J M.
Regional mitogenic response of the meniscus to plateret-derived-growth factor (PDGF-AB).
J Orthop Res.
1995;
13
201-207
-
73
Lietman S A, Hobbs W, Inoue N, Reddi A H.
Effects of selected growth factors on porcine meniscus in chemically defined medium.
Orthopedics.
2003;
26
799-803
-
74
Tumia N S, Johnstone A J.
Promoting the proliferative and synethtic activity of knee meniscal fibrochondrocytes using basic fibroblast growth factor in vitro.
AM J Sports Med.
2004;
4
915-920
-
75
Martinek V, Usas A, Pelinkovic D, Robbins P, Fu H H, Huard J.
Genetic engineering of meniscal allografts.
Tissue Eng.
2002;
8
107-117
-
76
Evans C H, Robbins P D.
Genetically augmented tissue engineering of the musculoskeletal system.
Clin Orthop.
1999;
367 (Suppl)
410-418
-
77
Goto H, Shuler F D, Lamsam D, Moller H D, Niybizi C, Fu F H, Robbins P D, Evans C H.
Transfer of LacZ Marker Gene to the meniscus.
J Bone Joint Surg [Am].
1999;
81
918-925
-
78
Upton M L, Chen J, Guilak F, Setton L A.
Differential effects of static and dynamic compresion on meniscal cell gene expression.
J Orthop Res.
2003;
21
963-969
-
79
Mueller S M, Shortkoff S, Schneider T O, Breinan H A, Yannas I V, Spector M.
Meniscus cells seeded in type 1 and type 2 collagen-GAG matrices in vitro.
Biomaterials.
1999;
20
701-709
-
80
Mueller S M, Schneider T O, Shortkoff S, Breinan H A, Spector M.
Alpha-smooth muscle actin and contractile behavior of bovine meniscus cells seeded in type 1 and type 2 collagen-GAG matrizes.
J Biomed Mater Res.
1999;
45
157-166
-
81
Ibbara C, Jannetta C, Vacanti C A, Cao Y, Upton J, Vacanti J P.
Tissue engineered meniscus: a potential new alternative to allogenic meniscus transplantation.
Transplant Proc.
1997;
29
986-988
-
82
Ibarra C, Koski J A, Warren R F.
Tissue engineering - Cells and matrix.
Orthop Clin North Am.
2000;
31
411-418
-
83
Peretti G M, Gill T J, Xu J W, Randolph M A, Morse K R, Zaleske D J.
Cell-therapy for meniscal repair: a large animal study.
Am J Sports Med.
2004;
32
146-158
-
84
Peretti G M, Caruso E M, Randolph M A, Zaleske D J.
Meniscal repair using engineered tissue.
J Orthop Res.
2001;
19
278-285
-
85
Ishimura M, Ohgushi H, Habata T, Tarnai S, Fuhisawa Y.
Arthroscopic meniscal repair using fibrin glue. Part I: Experimental study.
Arthroscopy.
1997;
13
551-557
-
86
Walsh C J, Goodmann D, Caplan A I, Goldberg V M.
Meniscus regeneration in a partial meniscectomy model.
Tissue Eng.
1999;
5
327-337
-
87
Port J, Jackson D W, Lee T Q, Simon T M.
Meniscal repair supplemented with exogenous fibrin clot and autogenous culture marrow cells in the goat model.
Am J Sports Med.
1996;
24
547-555
-
88
Murphy J M, Fink D J, Hunziker E B, Barry F P.
Stem cell therapy in a caprine model of osteoarthritis.
Arthritis Rheum.
2003;
48
3464-3474
Dr. med. Ralf Müller-Rath
Orthopädische Klinik · Universitätsklinikum Aachen
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