Subscribe to RSS
DOI: 10.1055/s-0030-1261964
© Georg Thieme Verlag KG Stuttgart · New York
Knochen Tissue Engineering zur Therapie von Knochendefekten
Bone Tissue Engineering for Bone Defect TherapyPublication History
eingereicht 15.11.2009
akzeptiert 25.6.2010
Publication Date:
06 September 2010 (online)
Zusammenfassung
Knochendefekte können zum Beispiel nach Tumorexzision oder Osteomyelitiden genauso auftreten wie nach Trauma bei Fraktur mit langer Defektstrecke, wenn die physiologische Reaktion auf einen Knochenbruch ausbleibt oder eine Pseudarthrose entsteht. In diesen Fällen wird eine chirurgische Intervention notwendig. Die Verwendung von autologen Knochentransplantaten aus z. B. Spongiosa, Kortikalis oder beidem sowie alternativ bei speziellen Indikationen die Kallusdistraktion stellen in solchen Fällen zumeist den heutigen Goldstandard dar. Bei größeren Defekten, ersatzschwachem Lager oder z. B. avaskulärer Knochennekrose kann ein gestieltes oder freies vaskularisiertes Knochentransplantat notwendig werden. Die Verfügbarkeit von autologen vaskularisierten Knochentransplantaten ist jedoch limitiert aufgrund einer unter Umständen signifikanten Hebemorbidität. Synthetische Knochenersatzstoffe, die entwickelt wurden, um die Grenzen des humanen Auto- und Allografts zu überwinden, stellen eine gute Alternative dar. Sie sind dazu in der Lage, Knochenneubildung in Knochendefekten kritischer Größe zu induzieren, aber sie bieten bis heute keine eigene Vaskularisation. Diese synthetischen Materialien bestehen aus einem großen Spektrum von unterschiedlichen Materialien, einschließlich natürlicher und synthetischer Polymere, Keramiken und zusammengesetzten Werkstoffen mit dem Ziel, den dreidimensionalen Charakter des Autografts zu imitieren und fungieren zum Teil als Vehikel für Wachstumsfaktoren, Antibiotika oder Zellen. Dieser Artikel gibt einen Überblick über den Einsatz von Matrix, Zellen und therapeutischen Substanzen im stetig wachsenden Feld des Knochen Tissue Engineerings.
Abstract
In critical size bone defects resulting from failed fracture healing or pseudarthrosis surgery is usually required. In this context, autologous bone grafts and callus distraction represent the gold standard, while sometimes even vascularised bone transfer is mandatory including microsurgical techniques. The availability of donor sites for such procedures is limited and the resulting morbidity significant. Therefore, synthetic bone grafts have been developed as an alternative. They consist of a broad range of different materials such as natural and synthetic polymers, ceramic and compound materials, aiming to mimic the three-dimensional character of autografts. In addition, they may act as a delivery vehicle for growth factors, antibiotics or cells. Their main limitation has been the lack of an intrinsic blood supply, limiting the potential for transplantation. This review provides an overview of matrices, cells and other therapeutic substances in the field of bone tissue engineering.
Schlüsselwörter
Knochen Tissue Engineering - bioartifizielles Knochengewebe - Vaskularisation - AV loop
Key words
bone tissue engineering - bone replacement - vascularisation - AV loop
Literatur
- 1 Soucacos PN, Dailiana Z, Beris AE. et al . Vascularised bone grafts for the management of non-union. Injury. 2006; 37 (S 01) S41-S50
- 2 Hierner R, Tager G, Nast-Kolb D. Die vaskularisierte Konchentransplantation. Unfallchirurg. 2009; 112 405-416 ; quiz 417–408
- 3 Malizos KN, Zalavras CG, Soucacos PN. et al . Free vascularized fibular grafts for reconstruction of skeletal defects. J Am Acad Orthop Surg. 2004; 12 360-369
- 4 Zimmermann CE, Borner BI, Hasse A. et al . Donor site morbidity after microvascular fibula transfer. Clin Oral Investig. 2001; 5 214-219
- 5 Buckwalter JA, Glimcher MJ, Cooper RR. et al . Bone biology. I: Structure, blood supply, cells, matrix, and mineralization. Instr Course Lect. 1996; 45 371-386
- 6 Aubin JE. Bone stem cells. J Cell Biochem Suppl. 1998; 30–31 73-82
- 7 Olsen BR, Reginato AM, Wang W. Bone development. Annu Rev Cell Dev Biol. 2000; 16 191-220
- 8 Probst A, Spiegel HU. Cellular mechanisms of bone repair. J Invest Surg. 1997; 10 77-86
- 9 Deschaseaux F, Sensebe L, Heymann D. Mechanisms of bone repair and regeneration. Trends Mol Med. 2009; 15 417-429
- 10 Schieker M, Mutschler W. Die Überbrückung von posttraumatischen Knochendefekten. Bewahrtes und Neues. Unfallchirurg. 2006; 109 715-732
- 11 Langer R, Vacanti JP. Tissue engineering. Science. 1993; 260 920-926
- 12 Gallico 3rd GG, O’Connor NE, Compton CC. et al . Permanent coverage of large burn wounds with autologous cultured human epithelium. N Engl J Med. 1984; 311 448-451
- 13 Vacanti JP, Morse MA, Saltzman WM. et al . Selective cell transplanta_tion using bioabsorbable artificial polymers as matrices. J Pediatr Surg. 1988; 23 3-9
- 14 Wakitani S, Kimura T, Hirooka A. et al . Repair of rabbit articular surfaces with allograft chondrocytes embedded in collagen gel. J Bone Joint Surg Br. 1989; 71 74-80
- 15 Thomson JA, Itskovitz-Eldor J, Shapiro SS. et al . Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282 1145-1147
- 16 Knight MA, Evans GR. Tissue engineering: progress and challenges. Plast Reconstr Surg. 2004; 114 E26-E37
- 17 Kneser U, Schaefer DJ, Polykandriotis E. et al . Tissue engineering of bone: the reconstructive surgeon's point of view. J Cell Mol Med. 2006; 10 7-19
- 18 Ikada Y. Challenges in tissue engineering. J R Soc Interface. 2006; 3 589-601
- 19 Giunta RE, Machens HG. Zur aktuellen Situation von Wissenschaft und Forschung der Plastischen Chirurgie in Deutschland. Handchir Mikrochir Plast Chir. 2009; 41 359-363
- 20 Cornell CN, Lane JM. Current understanding of osteoconduction in bone regeneration. Clin Orthop Relat Res. 1998; S267-S273
- 21 Hotz G, Herr G. Bone substitute with osteoinductive biomaterials – current and future clinical applications. Int J Oral Maxillofac Surg. 1994; 23 413-417
- 22 Cooper LF, Harris CT, Bruder SP. et al . Incipient analysis of mesenchymal stem-cell-derived osteogenesis. J Dent Res. 2001; 80 314-320
- 23 Bianco P, Robey PG. Stem cells in tissue engineering. Nature. 2001; 414 118-121
- 24 Musgrave DS, Bosch P, Ghivizzani S. et al . Adenovirus-mediated direct gene therapy with bone morphogenetic protein-2 produces bone. Bone. 1999; 24 541-547
- 25 Olivier V, Faucheux N, Hardouin P. Biomaterial challenges and approaches to stem cell use in bone reconstructive surgery. Drug Discov Today. 2004; 9 803-811
- 26 Schieker M, Heiss C, Mutschler W. . Unfallchirurg. 2008; 111 613-619 ; quiz 620
- 27 Ignatius AA, Betz O, Augat P. et al . In vivo investigations on composites made of resorbable ceramics and poly (lactide) used as bone graft substitutes. J Biomed Mater Res. 2001; 58 701-709
- 28 Carson JS, Bostrom MP. Synthetic bone scaffolds and fracture repair. Injury. 2007; 38 (S 01) S33-S37
- 29 Seitz H, Rieder W, Irsen S. et al . Three-dimensional printing of porous ceramic scaffolds for bone tissue engineering. J Biomed Mater Res B Appl Biomater. 2005; 74 782-788
-
30
Probst FA, Hutmacher DW, Muller DF. et al .
Calvarial Reconstruction by Customized Bioactive Implant.
Handchir Mikrochir Plast Chir.
- 31 Henkel KO, Gerber T, Lenz S. et al . Macroscopical, histological, and morphometric studies of porous bone-replacement materials in minipigs 8 months after implantation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 102 606-613
- 32 Lee K, Chan CK, Patil N. et al . Cell therapy for bone regeneration – bench to bedside. J Biomed Mater Res B Appl Biomater. 2009; 89 252-263
- 33 Eyckmans J, Roberts SJ, Schrooten J. et al . A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signaling. J Cell Mol Med. 2009;
- 34 Deschaseaux F, Pontikoglou C, Sensebe L. Bone regeneration: the stem/progenitor cells point of view. J Cell Mol Med. 2009;
-
35
Brayfield C, Marra K, Rubin JP.
Adipose stem cells for soft tissue regeneration.
Handchir Mikrochir Plast Chir.
42
124-128
- 36 Beltrami AP, Cesselli D, Bergamin N. et al . Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow). Blood. 2007; 110 3438-3446
- 37 Satija NK, Singh VK, Verma YK. et al . Mesenchymal Stem Cell-based Therapy: A New Paradigm in Regenerative Medicine. J Cell Mol Med. 2009;
- 38 Schieker M, Pautke C, Haasters F. et al . Human mesenchymal stem cells at the single-cell level: simultaneous seven-colour immunofluorescence. J Anat. 2007; 210 592-599
- 39 Mageed AS, Pietryga DW, DeHeer DH. et al . Isolation of large numbers of mesenchymal stem cells from the washings of bone marrow collection bags: characterization of fresh mesenchymal stem cells. Transplantation. 2007; 83 1019-1026
- 40 Rubin H. The role of selection in progressive neoplastic transformation. Adv Cancer Res. 2001; 83 159-207
- 41 De Ugarte DA, Morizono K, Elbarbary A. et al . Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs. 2003; 174 101-109
- 42 Tjabringa GS, Zandieh-Doulabi B, Helder MN. et al . The polymine spermine regulates osteogenic differentiation in adipose stem cells. J Cell Mol Med. 2008; 12 1710-1717
- 43 Kern S, Eichler H, Stoeve J. et al . Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006; 24 1294-1301
- 44 Sakaguchi Y, Sekiya I, Yagishita K. et al . Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum. 2005; 52 2521-2529
- 45 Liu H, Toh WS, Lu K. et al . A subpopulation of mesenchymal stromal cells with high osteogenic potential. J Cell Mol Med. 2009;
- 46 Noel D, Caton D, Roche S. et al . Cell specific differences between human adipose-derived and mesenchymal-stromal cells despite similar differentiation potentials. Exp Cell Res. 2008; 314 1575-1584
- 47 Tsiridis E, Upadhyay N, Giannoudis P. Molecular aspects of fracture healing: which are the important molecules?. Injury. 2007; 38 (S 01) S11-S25
- 48 Bielby R, Jones E, McGonagle D. The role of mesenchymal stem cells in maintenance and repair of bone. Injury. 2007; 38 (S 01) S26-S32
- 49 Niedhart C, Maus U, Redmann E. et al . Stimulation of bone formation with an in situ setting tricalcium phosphate/rhBMP-2 composite in rats. J Biomed Mater Res A. 2003; 65 17-23
- 50 Schmidmaier G, Schwabe P, Wildemann B. et al . Use of bone morphogenetic proteins for treatment of non-unions and future perspectives. Injury. 2007; 38 (S 04) S35-S41
- 51 Burkus JK, Sandhu HS, Gornet MF. et al . Use of rhBMP-2 in combination with structural cortical allografts: clinical and radiographic outcomes in anterior lumbar spinal surgery. J Bone Joint Surg Am. 2005; 87 1205-1212
- 52 Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery). J Tissue Eng Regen Med. 2008; 2 81-96
- 53 Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts). J Tissue Eng Regen Med. 2008; 2 1-13
- 54 Fu YC, Nie H, Ho ML. et al . Optimized bone regeneration based on sustained release from three-dimensional fibrous PLGA/HAp composite scaffolds loaded with BMP-2. Biotechnol Bioeng. 2008; 99 996-1006
- 55 Kanczler JM, Oreffo RO. Osteogenesis and angiogenesis: the potential for engineering bone. Eur Cell Mater. 2008; 15 100-114
- 56 Luo J, Sun MH, Kang Q. et al . Gene therapy for bone regeneration. Curr Gene Ther. 2005; 5 167-179
- 57 Wallmichrath J, Stark GB, Kneser U. et al . Epidermal growth factor (EGF) transfection of human bone marrow stromal cells in bone tissue engineering. J Cell Mol Med. 2008;
- 58 Böcker W, Yin Z, Drosse I. et al . Introducing a single-cell-derived human mesenchymal stem cell line expressing hTERT after lentiviral gene transfer. J Cell Mol Med. 2008; 12 1347-1359
- 59 Aslan H, Zilberman Y, Arbeli V. et al . Nucleofection-based ex vivo nonviral gene delivery to human stem cells as a platform for tissue regeneration. Tissue Eng. 2006; 12 877-889
- 60 Muschler GF, Nakamoto C, Griffith LG. Engineering principles of clinical cell-based tissue engineering. J Bone Joint Surg Am. 2004; 86-A 1541-1558
- 61 Volkmer E, Drosse I, Otto S. et al . Hypoxia in static and dynamic 3D culture systems for tissue engineering of bone. Tissue Eng Part A. 2008; 14 1331-1340
- 62 Seitz S, Ern K, Lamper G. et al . Influence of in vitro cultivation on the integration of cell-matrix constructs after subcutaneous implantation. Tissue Eng. 2007; 13 1059-1067
-
63
Volkmer E, Kallukalam BC, Maertz J. et al .
Hypoxic preconditioning of human mesenchymal stem cells overcomes hypoxia-induced inhibition of osteogenic differentiation.
Tissue Eng Part A.
16
153-164
- 64 Schneider M, Weitz J. Akuter Sauerstoffmangel und Hypoxietoleranz. Dtsch Med Wochenschr. 2008; 133 2168-2172
- 65 Alajati A, Laib AM, Weber H. et al . Spheroid-based engineering of a human vasculature in mice. Nat Methods. 2008; 5 439-445
- 66 Bleiziffer O, Horch RE, Hammon M. et al . T17b murine embryonal endothelial progenitor cells can be induced towards both proliferation and differentiation in a fibrin matrix. J Cell Mol Med. 2009; 13 926-935
- 67 Warnke PH, Springer IN, Wiltfang J. et al . Growth and transplantation of a custom vascularised bone graft in a man. Lancet. 2004; 364 766-770
- 68 Erol OO, Spira M. New capillary bed formation with a surgically constructed arteriovenous fistula. Surg Forum. 1979; 30 530-531
- 69 Wilson YT, Kumta S, Hickey MJ. et al . Use of free interpositional vein grafts as pedicles for prefabrication of skin flaps. Microsurgery. 1994; 15 717-721
- 70 Arkudas A, Tjiawi J, Bleiziffer O. et al . Fibrin gel-immobilized VEGF and bFGF efficiently stimulate angiogenesis in the AV loop model. Mol Med. 2007; 13 480-487
- 71 Arkudas A, Tjiawi J, Saumweber A. et al . Evaluation of blood vessel ingrowth in fibrin gel subject to type and concentration of growth factors. J Cell Mol Med. 2008;
- 72 Arkudas A, Beier JP, Heidner K. et al . Axial prevascularization of porous matrices using an arteriovenous loop promotes survival and differentiation of transplanted autologous osteoblasts. Tissue Eng. 2007; 13 1549-1560
- 73 Bach AD, Arkudas A, Tjiawi J. et al . A new approach to tissue engineering of vascularized skeletal muscle. J Cell Mol Med. 2006; 10 716-726
- 74 Beier JP, Horch RE, Arkudas A. et al . De novo generation of axially vascularized tissue in a large animal model. Microsurgery. 2009; 29 42-51
-
75
Beier JP, Horch RE, Hess A. et al .
Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model.
J Tissue Eng Regen Med.
4
216-223
- 76 Quarto R, Mastrogiacomo M, Cancedda R. et al . Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med. 2001; 344 385-386
- 77 Vacanti CA, Bonassar LJ, Vacanti MP. et al . Replacement of an avulsed phalanx with tissue-engineered bone. N Engl J Med. 2001; 344 1511-1514
- 78 Kitoh H, Kitakoji T, Tsuchiya H. et al . Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis – a preliminary result of three cases. Bone. 2004; 35 892-898
- 79 Marcacci M, Kon E, Moukhachev V. et al . Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study. Tissue Eng. 2007; 13 947-955
- 80 Cao Y, Vacanti JP, Paige KT. et al . Transplantation of chondrocytes utilizing a polymer-cell construct to produce tissue-engineered cartilage in the shape of a human ear. Plast Reconstr Surg. 1997; 100 297-302 ; discussion 303–294
Korrespondenzadresse
Anja Miriam Boos
Universitätsklinikum Erlangen
Plastisch- und Handchirurgische
Klinik
Krankenhausstraße 12
91054 Erlangen
Email: anja.boos@uk-erlangen.de