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Osteologie 2013; 22(03): 188-195
DOI: 10.1055/s-0038-1630123
Osteologische Biomaterialien
Schattauer GmbH

Bioreaktoren für Knochen-Tissue-Engineering

Bioreactors for bone tissue engineering
R. Pörtner
1   Institut für Bioprozess- und Biosystemtechnik, Technische Universität Hamburg-Harburg
,
H.-H. Hsu
1   Institut für Bioprozess- und Biosystemtechnik, Technische Universität Hamburg-Harburg
,
C. Goepfert
1   Institut für Bioprozess- und Biosystemtechnik, Technische Universität Hamburg-Harburg
› Author Affiliations
Further Information

Publication History

eingereicht: 02 June 2013

angenommen: 18 June 2013

Publication Date:
30 January 2018 (online)

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Zusammenfassung

Zur medizinischen Behandlung großer Knochendefekte oder Verletzungen werden als Alternative zu etablierten Behandlungs-methoden neue Konzepte des Tissue Engineering (TE) diskutiert. Beim Knochen-TE ist es das Ziel, eine mit Zellen besiedelte drei-dimensionale (3D), biologisch abbaubare Struktur am Ort der Verletzung zu implantieren. Techniken für die organotypische Kultivierung von Knochenzellen in vitro beruhen auf der Kultivierung von Gewebezellen in Bioreaktoren in einem definierten Kultur-medium auf porösen Matrizes (Scaffolds), um ein gewebeähnliches Wachstum in 3D-Strukturen zu ermöglichen. Ein wichtiger Faktor für die erfolgreiche 3D-Kultur ist die Schaffung adäquater Strömungsbedingungen, die wiederum Einfluss auf die biochemischen und biophysikalischen (z. B. mechanische) Reize haben, denen die Zellen ausgesetzt sind. Hier müssen neben Schereffekten auch Stofftransportlimitierungen berücksichtigt werden. Der Beitrag fasst den aktuellen Stand bei der Entwicklung von Bioreaktoren für die Generierung von Knochenersatzmaterialien zusammen.

Summary

For the medical treatment of large bone defects or injuries new concepts of tissue engineering (TE) are discussed as an alternative to established methods of treatment. The goal of bone-TE is the implantation of threedimensional (3D), biodegradable implants seeded with bone cells at the site of injury. Techniques for the organotypic culture of bone cells in vitro are based on the cultivation of tissue cells in a defined culture medium in bioreactors on porous matrices (scaffolds) to allow a tissue-like three-dimensional growth. An important factor for successful 3D culture is the creation of adequate flow conditions, which in turn influence the biochemical and biophysical (e. g. fluidmechanical) stimuli to which the cells are exposed. Here also mass transport limitations must be considered in addition to shear effects. The article summarizes the current state of the art with respect to development of bioreactors for the generation of bone implants.

Schlüsselwörter

Tissue Engineering - Knochen - Bioreaktor - Perfusion

Keywords

Tissue engineering - bone - bioreactor - perfusion
 

  • References

  • 1 Jakob F, Ebert R, Ignatius A. et al. Bone tissue engineering in osteoporosis. Maturitas. 2013 DOI 10.1016/j.maturitas.2013.03.004.
    PubMedGoogle Scholar
  • 2 Schmidt-Rohlfing B, Tzioupis C, Menzel CL, Pape HC. Tissue Engineering von Knochengewebe: Prinzipien und klinische Anwendungsmöglichkeiten. Unfallchirurg 2009; 112 (9) 785-794.
    CrossrefPubMedGoogle Scholar
  • 3 Nukavarapu SP, Dorcemus DL. Osteochondral tissue engineering: Current strategies and challenges. Biotechnol Adv. 2012 DOI 10.1016/j.biotechadv.2012.11.004.
    PubMedGoogle Scholar
  • 4 Pörtner R, Burger Ch, Maier-Reif K. et al. Organotypic Tissue Cultures for Substance Testing – A Survey of Academic and Industrial Activities in Germany. BIOforum Europe 2010; 3: 21-23.
    Google Scholar
  • 5 Gaspar D, Gomide V, Monteiro F. The role of perfusion bioreactors in bone tissue engineering. Biomatter 2012; 2 (4) 167-175.
    CrossrefPubMedGoogle Scholar
  • 6 Yeatts AB, Geibel EM, Fears FF, Fisher J. Human mesenchymal stem cell position within scaffolds influences cell fate during dynamic culture. Biotechnol Bioeng 2012; 109 (9) 2381-2391.
    CrossrefPubMedGoogle Scholar
  • 7 Bjerre L, Bünger C, Baatrup A. et al. Flow perfusion culture of human mesenchymal stem cells on coralline hydroxyapatite scaffolds with various pore sizes. J Biomed Mater Res A 2011; 97: 251-263.
    PubMedGoogle Scholar
  • 8 Martin I, Wendt D, Heberer M. The role of bioreactors in tissue engineering. Trends Biotechnol 2004; 22: 80-86.
    CrossrefPubMedGoogle Scholar
  • 9 Allori AC, Sailon A, Warren SM. Biological basis of bone formation, remodelling and repair – Part III: Biomechanical forces. Tissue Eng 2008; 14 (3) B 285-293.
    Google Scholar
  • 10 Kim HJ, Kim UJ, Leisk GG. et al. Bone regeneration on macroporous aqueous-derived silk 3-D scaffolds. Macromol Biosci 2007; 7: 643-655.
    CrossrefPubMedGoogle Scholar
  • 11 Liu L, Yu B, Chen J. et al. Different effects of intermittent and continuous fluid shear stresses on osteogenic differentiation of human mesenchymal stem cells. Biomech Model Mechanobiol 2012; 11 (3-4) 391-401.
    CrossrefPubMedGoogle Scholar
  • 12 Weinbaum S, Cowin SC, Zeng Y. A model for the excitation of osteocytes by mechanical loading induced bone fluid shear stresses. J Biomechanics 1994; 27: 339-360.
    CrossrefPubMedGoogle Scholar
  • 13 Holtorf HL, Sheffield TL, Ambrose CG. et al. Flow perfusion culture of marrow stromal cells seeded on porous biphasic calcium phosphate ceramics. Annals Biomed Eng 2005; 33 (9) 1238-1248.
    CrossrefPubMedGoogle Scholar
  • 14 Bjerre L, Bünger CE, Kassem M, Mygind T. Flow perfusion culture of human mesenchymal stem cells on silicate-substituted tricalcium phosphate scaffolds. Biomaterials 2008; 29: 2616-2627.
    CrossrefPubMedGoogle Scholar
  • 15 Datta N, Pham QP, Sharma U. et al. In vitro generated extracellular matrix and fluid shear stress synergistically enhance 3D osteoblastic differentiation. PNAS 2006; 103 (8) 2488-2493.
    CrossrefPubMedGoogle Scholar
  • 16 Zhao F, Chella R, Ma T. Effects of shear stress on 3-D human mesenchymal stem cell construct development in a perfusion bioreactor system: Experiments and hydrodynamic modeling. Biotechnol Bioeng 2007; 96: 584-595.
    CrossrefPubMedGoogle Scholar
  • 17 Wang L, Hu Y-Y, Wang Z. et al. Flow perfusion of human fetal bone cells in large beta-tricalcium phosphate scaffold with controlled architecture. J Biomed Mat Res Part A. 2008 DOI 10.1002/jbm.a.32189.
    PubMedGoogle Scholar
  • 18 Maes F, van Ransbeeck P, van Oosterwyck H, Verdonck P. Modeling fluid flow through irregular scaffolds for perfusion bioreactors. Biotechnol Bioeng 2009; 103 (3) 621-630.
    CrossrefPubMedGoogle Scholar
  • 19 Chen Y, Zhou S, Cadman J, Li Q. Design of cellular porous biomaterials for wall shear stress criterion. Biotechnol Bioeng 2010; 107 (4) 737-746.
    CrossrefPubMedGoogle Scholar
  • 20 Pörtner R, Nagel-Heyer St, Goepfert Ch. et al. Bioreactor design for tissue engineering. J Biosci Bioeng 2005; 100 (3) 235-245.
    CrossrefPubMedGoogle Scholar
  • 21 Ceccarelli G, Bloise N, Vercellino M. et al. In vitro osteogenesis of human stem cells by using a three-dimensional perfusion bioreactor culture system: a review. Recent Pat Drug Deliv Formul 2013; 7 (1) 29-38.
    CrossrefPubMedGoogle Scholar
  • 22 Maxson S, Orr D, Burg KJL. Bioreactors for Tissue Engineering. Tissue Engineering 2011; 179-197. DOI 10.1007/978-3-642-02824-3_10.
    Google Scholar
  • 23 Rauh J, Milan F, Günther K-P, Stiehler M. Bioreactor systems for bone tissue engineering. Tissue Eng Part B Rev 2011; 17 (4) 263-280.
    CrossrefPubMedGoogle Scholar
  • 24 Wendt D, Riboldi SA, Cioffi M, Martin I. Bioreactors in tissue engineering: scientific challenges and clinical perspectives. Adv Biochem Eng Biotechnol 2009; 112: 1-27.
    PubMedGoogle Scholar
  • 25 Goh TK-P, Zhang Z-Y, Chen AK-L. et al. Microcarrier culture for efficient expansion and osteogenic differentiation of human fetal mesenchymal stem cells. Biores Open Access 2013; 2 (2) 84-97.
    CrossrefPubMedGoogle Scholar
  • 26 Yuan Y, Kallos MS, Hunter Ch, Sen A. Improved expansion of human bone marrow-derived mesenchymal stem cells in microcarrier-based suspension culture. J Tissue Eng Regen Med. 2012 DOI 10.1002/term.1515.
    PubMedGoogle Scholar
  • 27 Fassnacht D, Pörtner R. Experimental and theoretical considerations on oxygen supply for animal cell growth in fixed bed reactors. J Biotechnol 1999; 72: 169-184.
    CrossrefPubMedGoogle Scholar
  • 28 Rojewski M, Fekete N, Baila St. et al. GMP-compliant isolation and expansion of bone marrow-derived MSCs in the closed, automated device Quantum Cell Expansion system. Cell Transplant. 2012 DOI 10.3727/096368912X657990.
    PubMedGoogle Scholar
  • 29 Eibl R, Eibl D. Application of disposable bag bioreactors in tissue engineering and for the production of therapeutic agents. Adv Biochem Eng Biotechnol 2009; 112: 183-207.
    PubMedGoogle Scholar
  • 30 Vetsch JR, Müller R, Hofmann S. The evolution of simulation techniques for dynamic bone tissue engineering in bioreactors. J Tissue Eng Regen Med. 2013 DOI 10.1002/term.1733.
    PubMedGoogle Scholar
  • 31 Weber Ch, Freimark D, Pörtner R. et al. Expansion of human mesenchymal stem cells in a fixed-bed bioreactor system based on non-porous glass carrier – Part B: Modeling and scale up of the system. Int J Artif Organs 2010; 33 (11) 782-795.
    CrossrefPubMedGoogle Scholar
  • 32 Fan J, Jia X, Huang Y. et al. Greater scaffold permeability promotes growth of osteoblastic cells in a perfused bioreactor. J Tissue Eng Regen Med. 2013 DOI 10.1002/term.1701.
    PubMedGoogle Scholar
  • 33 Mohebbi-Kalhori D, Behzadmehr A, Doillon ChJ, Hadjizadeh A. Computational modeling of adherent cell growth in a hollow-fiber membrane bioreactor for large-scale 3-D bone tissue engineering. J Artif Organs 2012; 15 (3) 250-265.
    CrossrefPubMedGoogle Scholar
  • 34 Suck K, Behr L, Fischer M. et al. Cultivation of MC3T3-E1 cells on a newly developed material (Sponceram) using a rotating bed system bioreactor. J Biomed Mater Res A 2007; 80 (2) 268-275.
    PubMedGoogle Scholar
  • 35 Diederichs S, Röker St, Marten D. et al. Dynamic cultivation of human mesenchymal stem cells in a rotating bed bioreactor system based on the Z RP platform. Biotechnol Prog 2009; 25 (6) 1762-1771.
    PubMedGoogle Scholar
  • 36 Suck K, Roeker St, Diederichs S. et al. A rotating bed system bioreactor enables cultivation of primary osteoblasts on well-characterized Sponceram regarding structural and flow properties. Biotechnol Prog 2010; 26 (3) 671-678.
    CrossrefPubMedGoogle Scholar
  • 37 van Griensven M, Diederichs S, Roeker S. et al. Mechanical Strain Using 2D and 3D Bioreactors Induces Osteogenesis: Implications for Bone Tissue Engineering. Adv Biochem Eng Biotechnol 2009; 112: 95-123.
    PubMedGoogle Scholar
  • 38 Burton VJ, Ciuclan LI, Holmes AM. et al. Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function. Blood 2011; 117 (1) 333-341.
    CrossrefPubMedGoogle Scholar
  • 39 Hussein MA, Esterl S, Pörtner R. et al. On the Lattice Boltzmann Method Simulation of a two Phase Flow Bioreactor for Artificially Grown Cartilage Cells. J Biomech 2008; 41 (16) 3455-3461.
    CrossrefPubMedGoogle Scholar
  • 40 Fischer J, Pörtner R, Feyerabend F. et al. Bioreactor Test Set Up for in vitro Cytocompatiblity Testing of Magnesium Materials, 2nd Symposium on Biodegradable Metals. 31.08.-03.09.2010 Maratea, Italien.:
    Google Scholar
  • 41 Oheim R, Beil FT, Barvencik F. et al. Großtiermodelle der Osteoporose. Osteologie 2011; 20 (1) 41-49.
    Article in Thieme ConnectGoogle Scholar
  • 42 Tonak M, Kurth AA. Füllmaterialien und adjuvante Agenzien in der lokalen Behandlung benigner Knochentumoren und tumorähnlicher Läsionen. Osteologie 2010; 19 (4) 340-345.
    Article in Thieme ConnectGoogle Scholar
  • 43 Seefried L, Ebert R, Müller-Deubert S. et al. Mechanotransduktion im Alter und bei Osteoporose. Osteologie 2010; 19 (3) 232-239.
    Article in Thieme ConnectGoogle Scholar
  • 44 Felsenberg D. Muskuloskelettale Anpassung bei Immobilisation. Osteologie 2010; 19 (3) 210-215.
    Article in Thieme ConnectGoogle Scholar