Bioreactor design for tissue engineering.

Bioreactor systems play an important role in tissue engineering, as they enable reproducible and controlled changes in specific environmental factors. They can provide technical means to perform controlled studies aimed at understanding specific biological, chemical or physical effects. Furthermore, bioreactors allow for a safe and reproducible production of tissue constructs. For later clinical applications, the bioreactor system should be an advantageous method in terms of low contamination risk, ease of handling and scalability. To date the goals and expectations of bioreactor development have been fulfilled only to some extent, as bioreactor design in tissue engineering is very complex and still at an early stage of development. In this review we summarize important aspects for bioreactor design and provide an overview on existing concepts. The generation of three dimensional cartilage-carrier constructs is described to demonstrate how the properties of engineered tissues can be improved significantly by combining biological and engineering knowledge. In the future, a very intimate collaboration between engineers and biologists will lead to an increased fundamental understanding of complex issues that can have an impact on tissue formation in bioreactors.

[1]  C. V. van Blitterswijk,et al.  Low oxygen tension stimulates the redifferentiation of dedifferentiated adult human nasal chondrocytes. , 2003, Osteoarthritis and cartilage.

[2]  G. Terenghi.  Tissue Engineering Methods and Protocols. Edited by JEFFREY R. MORGAN and MARTIN L. YARMUSH. (Pp. xvi+629; illustrated; $99 hardback; ISBN 0 896 03516 6.) Totowa, New Jersey: Humana. 1998. , 1999 .

[3]  B Kurz,et al.  Redifferentiation of dedifferentiated bovine articular chondrocytes in alginate culture under low oxygen tension. , 2002, Osteoarthritis and cartilage.

[4]  C. Krettek,et al.  Tissue-Engineering von Röhrenknochen mit einer vaskularisierten Matrix in einem Bioreaktor , 2004, Der Orthopäde.

[5]  A. Grodzinsky,et al.  Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix , 1992, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[6]  G. B. Fiore,et al.  Mechanobiology of engineered cartilage cultured under a quantified fluid-dynamic environment , 2002, Biomechanics and modeling in mechanobiology.

[7]  U. Marx,et al.  HUMAN CANCER AND PRIMARY CELL CULTURE IN THE NEW HYBRID BIOREACTOR SYSTEM TECNOMOUSE , 1994 .

[8]  Clemens A van Blitterswijk,et al.  Cartilage Tissue Engineering: Controversy in the Effect of Oxygen , 2003, Critical reviews in biotechnology.

[9]  J. Davies,et al.  Engineering three-dimensional bone tissue in vitro using biodegradable scaffolds: investigating initial cell-seeding density and culture period. , 2000, Journal of biomedical materials research.

[10]  D. Fassnacht,et al.  Influence of bcl-2 on antibody productivity in high cell density perfusion cultures of hybridoma , 1999, Cytotechnology.

[11]  Joseph P Vacanti,et al.  Hepatic tissue engineering. , 2004, Transplant immunology.

[12]  Smadar Cohen,et al.  Cardiac Tissue Engineering, Ex-Vivo: Design Principles in Biomaterials and Bioreactors , 2003, Heart Failure Reviews.

[13]  H. Jockusch,et al.  Growth and differentiation of permanent and secondary mouse myogenic cell lines on microcarriers , 2001, Applied Microbiology and Biotechnology.

[14]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[15]  Alexander M Seifalian,et al.  The roles of tissue engineering and vascularisation in the development of micro-vascular networks: a review. , 2005, Biomaterials.

[16]  M. Fussenegger,et al.  Regulated overexpression of the survival factor bcl-2 in CHO cells increases viable cell density in batch culture and decreases DNA release in extended fixed-bed cultivation , 2004, Cytotechnology.

[17]  A. Bader,et al.  Bioreactor developments for tissue engineering applications by the example of the bioartificial liver. , 2002, Advances in biochemical engineering/biotechnology.

[18]  C. Wandrey,et al.  Cultivation of hematopoietic stem and progenitor cells: biochemical engineering aspects. , 2002, Advances in biochemical engineering/biotechnology.

[19]  C. V. van Blitterswijk,et al.  Effect of oxygen tension on adult articular chondrocytes in microcarrier bioreactor culture. , 2004, Tissue engineering.

[20]  A. Bader,et al.  Review of a flat membrane bioreactor as a bioartificial liver. , 2001, Annals of transplantation.

[21]  F J Schoen,et al.  Cardiac tissue engineering: cell seeding, cultivation parameters, and tissue construct characterization. , 1999, Biotechnology and bioengineering.

[22]  D L Butler,et al.  Functional tissue engineering: the role of biomechanics. , 2000, Journal of biomechanical engineering.

[23]  R. Mason,et al.  Responses of articular cartilage explant cultures to different oxygen tensions. , 1994, Biochimica et biophysica acta.

[24]  Ralf Pörtner,et al.  Perfusion cultures and modelling of oxygen uptake with three-dimensional chondrocyte pellets , 1999 .

[25]  S W O'Driscoll,et al.  Role of oxygen tension during cartilage formation by periosteum , 1997, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[26]  F. Cerra,et al.  Gel-entrapment bioartificial liver therapy in galactosamine hepatitis. , 1995, The Journal of surgical research.

[27]  Makarand V Risbud,et al.  Tissue engineering: advances in in vitro cartilage generation. , 2002, Trends in biotechnology.

[28]  G. Naughton,et al.  From Lab Bench to Market , 2002 .

[29]  G. Vunjak‐Novakovic,et al.  Frontiers in tissue engineering. In vitro modulation of chondrogenesis. , 1999, Clinical orthopaedics and related research.

[30]  I. Kwon,et al.  Tissue engineering of urinary organs. , 2000, Yonsei medical journal.

[31]  P. E. McHugh,et al.  Bioreactors for Cardiovascular Cell and Tissue Growth: A Review , 2003, Annals of Biomedical Engineering.

[32]  S. Kleis,et al.  The fluid dynamic and shear environment in the NASA/JSC rotating-wall perfused-vessel bioreactor. , 2000, Biotechnology and bioengineering.

[33]  M J Lysaght,et al.  Demographic Scope and Economic Magnitude of Contemporary Organ Replacement Therapies , 2000, ASAIO journal.

[34]  P. Czermak,et al.  Experimental and modeling study of a membrane filtration process using ceramic membranes to increase retroviral pseudotype vector titer , 2004 .

[35]  T. Wick,et al.  Computational Fluid Dynamics Modeling of Steady‐State Momentum and Mass Transport in a Bioreactor for Cartilage Tissue Engineering , 2002, Biotechnology progress.

[36]  U. Marx,et al.  Application of a hollow fiber membrane cell culture system in medicine. , 1993, American biotechnology laboratory.

[37]  J M Davis,et al.  Hollow-fiber cell culture. , 1997, Methods in molecular biology.

[38]  R. Chamuleau.  Artificial Liver Support in the Third Millennium , 2003, Artificial cells, blood substitutes, and immobilization biotechnology.

[39]  I. Behn,et al.  Cultivation of Animal Cells in a New Modular Minifermenter , 1995 .

[40]  C. Oomens,et al.  An integrated finite-element approach to mechanics, transport and biosynthesis in tissue engineering. , 2004, Journal of biomechanical engineering.

[41]  Y S Morsi,et al.  Artificial Aortic Valves: An Overview , 2004, The International journal of artificial organs.

[42]  J. B. Griffiths,et al.  Animal Cell Technology: Products of Today, Prospects for Tomorrow , 1994 .

[43]  A. Atala,et al.  In Vitro Systems for Tissue Engineering , 2002, Annals of the New York Academy of Sciences.

[44]  R. Pörtner,et al.  Experimental and theoretical considerations on oxygen supply for animal cell growth in fixed-bed reactors. , 1999, Journal of biotechnology.

[45]  A. Ratcliffe.  Tissue engineering of vascular grafts. , 2000, Matrix biology : journal of the International Society for Matrix Biology.

[46]  Ralf Pörtner,et al.  Long-term cultivation of immortalised mouse hepatocytes in a high cell density, fixed-bed reactor , 1998 .

[47]  J. Gerlach,et al.  Development of a Hybrid Liver Support System: A Review , 1996, The International journal of artificial organs.

[48]  Cláudia Lobato da Silva,et al.  Hematopoietic stem cells: from the bone to the bioreactor. , 2003, Trends in biotechnology.

[49]  Michael S Kallos,et al.  New tissue dissociation protocol for scaled-up production of neural stem cells in suspension bioreactors. , 2004, Tissue engineering.

[50]  W W Minuth,et al.  Artificial Tissues in Perfusion Culture , 1997, The International journal of artificial organs.

[51]  Michimasa Kishimoto,et al.  An attempt at decision making in tissue engineering: reactor evaluation using the analytic hierarchy process (AHP) , 2004 .

[52]  J. Vacanti,et al.  Tissue engineering. , 1993, Science.

[53]  J. B. Griffiths,et al.  Animal Cell Technology: Developments Towards the 21st Century , 1995, Springer Netherlands.

[54]  G. Vunjak‐Novakovic,et al.  Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage. , 1999, Biotechnology and bioengineering.

[55]  M. Morlock,et al.  Relationship between physical, biochemical and biomechanical properties of tissue-engineered cartilage-carrier-constructs , 2005, Biotechnology Letters.

[56]  G. Naughton,et al.  From lab bench to market: critical issues in tissue engineering. , 2002, Annals of the New York Academy of Sciences.

[57]  G. Vunjak‐Novakovic.  The fundamentals of tissue engineering: scaffolds and bioreactors. , 2003, Novartis Foundation symposium.

[58]  Cato T Laurencin,et al.  Bioreactor-based bone tissue engineering: the influence of dynamic flow on osteoblast phenotypic expression and matrix mineralization. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[59]  C. Heath,et al.  Influence of intermittent pressure, fluid flow, and mixing on the regenerative properties of articular chondrocytes. , 1999, Biotechnology and bioengineering.

[60]  Sangeeta N Bhatia,et al.  Improving the next generation of bioartificial liver devices. , 2002, Seminars in cell & developmental biology.

[61]  Anthony Ratcliffe,et al.  Bioreactors and Bioprocessing for Tissue Engineering , 2002, Annals of the New York Academy of Sciences.

[62]  Seonghun Park,et al.  Functional tissue engineering of chondral and osteochondral constructs. , 2004, Biorheology.

[63]  J. Tramper,et al.  Oxygen gradients in tissue‐engineered Pegt/Pbt cartilaginous constructs: Measurement and modeling , 2004, Biotechnology and bioengineering.

[64]  J. Urban,et al.  The effects of hydrostatic pressure on matrix synthesis in articular cartilage , 1991, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[65]  S E Carver,et al.  Increasing extracellular matrix production in regenerating cartilage with intermittent physiological pressure. , 1999, Biotechnology and bioengineering.

[66]  W. Knauf,et al.  Culture of haematopoietic cells in a 3-D bioreactor made of Al2O3 or apatite foam , 2004, Journal of materials science. Materials in medicine.

[67]  R Langer,et al.  Long-term culture of tissue engineered cartilage in a perfused chamber with mechanical stimulation. , 2004, Biorheology.

[68]  L. Griffith,et al.  Tissue Engineering--Current Challenges and Expanding Opportunities , 2002, Science.

[69]  Gerard A Ateshian,et al.  Modeling of neutral solute transport in a dynamically loaded porous permeable gel: implications for articular cartilage biosynthesis and tissue engineering. , 2003, Journal of biomechanical engineering.

[70]  R. Dermietzel,et al.  Construction of an apparatus for perfusion cell cultures which enables in vitro experiments under organotypic conditions. , 1992, European journal of cell biology.

[71]  G. Vunjak‐Novakovic,et al.  Tissue engineering of cartilage in space. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[72]  Kyriacos A Athanasiou,et al.  Articular cartilage bioreactors and bioprocesses. , 2003, Tissue engineering.

[73]  J E Prenosil,et al.  Automated production of cultured epidermal autografts and sub-confluent epidermal autografts in a computer controlled bioreactor. , 1998, Biotechnology and bioengineering.

[74]  J. Connelly,et al.  The influence of cyclic tension amplitude on chondrocyte matrix synthesis: experimental and finite element analyses. , 2004, Biorheology.

[75]  J. Petersen,et al.  Present and Future Therapies of Articular Cartilage Defects , 2003, European Journal of Trauma.

[76]  D. Wendt,et al.  The role of bioreactors in tissue engineering. , 2004, Trends in biotechnology.

[77]  S. Waldman,et al.  Characterization of cartilagenous tissue formed on calcium polyphosphate substrates in vitro. , 2002, Journal of biomedical materials research.

[78]  G. Vunjak‐Novakovic,et al.  Frontiers in Tissue Engineering , 1999 .