Advanced Bioreactor with Controlled Application of Multi-Dimensional Strain For Tissue Engineering

[+] Author and Article Information
Gregory H. Altman, Helen H. Lu, Rebecca L. Horan, Tara Calabro, Daniel Ryder, David L. Kaplan

Tufts University, Department of Chemical & Biological Engineering, Bioengineering Center, 4 Colby Street, Medford, MA 02155

Peter Stark

Harvard Medical School, Center for Technology & Engineering, Boston, MA

Ivan Martin

University Hospital Basel, Department of Surgery, Research Division, 4031 Basel, Switzerland

John C. Richmond

New England Medical Center, Department of Orthopaedics, Boston, MA 02111

Gordana Vunjak-Novakovic

Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge, MA 02139

J Biomech Eng 124(6), 742-749 (Dec 27, 2002) (8 pages) doi:10.1115/1.1519280 History: Received October 01, 2001; Revised July 01, 2002; Online December 27, 2002
Copyright © 2002 by ASME
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Chiquet-Ehrismann,  R., Tannheimer,  M., Koch,  M., Brunner,  A., Spring,  J., Martin,  D., Baumgartner,  S., and Chiquet,  M., 1994, “Tenascin-C Expression by Fibroblasts is Elevated in Stressed Collagen Gels,” J. Cell Biol., 127, pp. 2093–2101.
Goulet, F., Germain, L., Rancourt, D., Caron, C., Normand, A., and Auger, F. A., 1997, “Tendons and Ligaments,” Principles of Tissue Engineering, R. Lanza, R. Langer, and W. Chick, eds., R. G. Landes Co., pp. 633–643.
Trachslin,  J., Koch,  M., and Chiquet,  M., 1999, “Rapid and Reversible Regulation of Collagen XII Expression by Changes in Tensile Strength,” Exp. Cell Res., 247, pp. 320–328.
Kim,  B. S., Nikolovski,  J., Bonadio,  J., and Mooney,  D. J., 1999, “Cyclic Mechanical Strain Regulates the Development of Engineered Smooth Muscle Tissue,” Nat. Biotechnol., 17, pp. 979–983.
Toyoda,  T., Matsumoto,  H., Fujikawa,  K., Saito,  S., and Inoue,  K., 1998, “Tensile Load and the Metabolism of Anterior Cruciate Ligament,” Clin. Orthop. Relat. Res. 353, pp. 247–255.
Langelier,  E., Rancourt,  D., Bouchard,  S., Lord,  C., Stevens,  P. P., Germain,  L., and Auger,  F. A., 1999, “Cyclic Traction Machine for Long-Term Culture of Fibroblast-Populated Collagen Gels,” Ann. Biomed. Eng., 27, pp. 67–72.
Frank,  E. H., Jin,  M., Loening,  A. M., Levenston,  M. E., and Grodzinsky,  A. J., 2000, “A Versatile Shear and Compression Apparatus for Mechanical Stimulation of Tissue Culture Explants,” J. Biomech., 33, pp. 1523–1527.
Sodian,  R., Lemke,  T., Loebe,  M., Hoerstrup,  S. P., Potapov,  E. V., Hausmann,  H., Meyer,  R., and Hetzer,  R., 2001, “New Pulsatile Bioreactor for Fabrication of Tissue-Engineered Patch,” J. Biomed. Mater. Res., 58, pp. 401–405.
Vunjak-Novakovic,  G., Martin,  I., Obradovic,  B., Treppo,  S., Grodzinsky,  A. J., Langer,  R., and Freed,  L., 1999, “Bioreactor Cultivation Conditions Modulate the Composition and Mechanical properties of Tissue Engineered Cartilage,” J. Orthop. Res., 17, pp. 130–138.
Gooch, K. J., Blunk, T., Tennant, C. J., Vunjak-Novakovic G., Langer, R., and Freed, L. E., 1998, “Mechanical Forces and Growth Factors Utilized in Tissue Engineering,” Frontiers in Tissue Engineering, C. Patrick, A. Mikos, and L. McIntire, eds, Pergamon, pp. 61–82.
Freed L. E., Vunjak-Novakovic, G., 1995, “Tissue Engineering of Cartilage,” The Biomedical Engineering Handbook, J. D. Bronzino, ed., CRC Press, pp. 1778–1796.
Freed, L. E., and Vunjak-Novakovic, G., 1997, “Tissue Culture Bioreactors: Chondrogenesis as a Model System,” Principles of Tissue Engineering, R. P. Lanza, R. Langer, and W. L. Chick, eds., Landes and Springer, pp. 153–167.
Freed,  L. E., and Vunjak-Novakovic,  G., 1998, “Culture of Organized Cell Communities,” Adv. Drug Delivery Rev., 33(1–2), pp. 15–30.
Bursac,  N., Papadaki,  M., Cohen,  R. J., Schoen,  F. J., Eisenberg,  S. R., Carrier,  R., Vunjak-Novakovic,  G., and Freed,  L. E., 1999, “Cardiac muscle tissue engineering: towards an in vitro model for electrophysiological studies,” Am. J. Physiol., 277, pp. H433–44.
Carrier,  R., Papadaki,  M., Rupnick,  M., Schoen,  F. J., Bursac,  N., Langer,  R., Freed,  L. E., and Vunjak-Novakovic,  G., 1999, “Cardiac Tissue Engineering: Cell Seeding, Cultivation Parameters and Tissue Construct Characterization,” Biotechnol. Bioeng., 64, pp. 580–589.
Papadaki,  M., Bursac,  N., Langer,  R., Merok,  J., Vunjak-Novakovic,  G., and Freed,  L. E., 2001, “Tissue Engineering of Functional Cardiac Muscle: Molecular, Structural and Electrophysiological Evaluations,” Am. J. Physiol. Heart Circ. Physio., 280 , pp. H168–H178.
Niklason,  L. E., Gao,  J., Abbott,  W. M., Hirschi,  K. K., Houser,  S., Marini,  R., and Langer,  R., 1999, “Functional Arteries Grown In Vitro,” Science, 284, pp. 489–493.
Woo, SL-Y., Young, E. P., and Kwan, M. K., 1990, “Fundamental Studies in Knee Ligament Mechanics,” Knee Ligaments: Structure, Function, Injury and Repair, D. Daniel, et al., eds. Raven Press, pp. 115–134.
Fermor,  B., Urban,  J., Murray,  D., Pocock,  A., Lim,  E., Francis,  M., and Gage,  J., 1998, “Proliferation and Collagen Synthesis of Human Anterior Cruciate Ligament Cells In Vitro: Effects of Ascorbate-2-phosphate, Dexamethasone and Oxygen Tension,” Cell Biol. Int., 22, pp. 635–640.
Pittenger,  M. F., Mackay,  A. M., Beck,  S. C., Jaiswal,  R. K., Douglas,  R., Moscas,  J. D., Moorman,  M. A., Simonetti,  D. W., Craig,  S., and Marshak,  D. R., 1999, “Multilineage Potential of Adult Human Mesenchymal Stem Cells,” Science, 284, pp. 143–147.
Seshi,  B., Kumar,  S., and Sellers,  D., 2000, “Human Bone Marrow Stromal Cell: Coexpression of Markers Specific for Multiple Mesenchymal Cell Lineages,” Blood Cells Mol. Dis., 26(3), pp. 234–246.
Altman,  G. H., Horan,  R. L., Stark,  P. R. H., Martin,  I., Farhadi,  J., Richmond,  J. C., Vunjak-Novokovic,  G., and Kaplan,  D. L., 2001, “Cell Differentiation by Mechanical Stress,” FASEB J., 16, pp. 270–272 (print) and 10.1096 (electronic).


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A . Schematic illustrating the bioreactor system. B . Functioning bioreactor system including (a) peristaltic pump, (b) environmental gas chamber and (c) the two bioreactors containing 24 vessels.
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A . Exploded-view of the reactor vessel assembly. B . Reactor vessel containing an anchored silk fiber matrix during culture with seeded hBMSCs. Vessel ‘seats’ (a) within the fixed-position plates and vessel locking bar (b) are shown.
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A . System bioreactors (a) with 24 loaded reactor vessels (b). The traveler (c) housing both rotational (in view) and translational gear trains, the high torque stepper motors (d), and the linear bearing (e) are shown. B . Chart illustrating empirical translational and rotational displacement data for a programmed 10 cycle 2 mm and 90° regime at 0.0167 Hz.
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Environmental chamber prior to closure to show the internal silicone hose coils and gas inlet distribution manifold
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Experimental data of pH and pO2 levels measured during a 21 day experiment
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Scanning electron micrographs of hBMSCs seeded on the silk fiber scaffold (A) 1 hr post-seeding prior to loading into the reactor, and (B) grown in the bioreactor for 14 days. The arrow indicates cell sheet and possible extra-cellular matrix formation.
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A . H&E of mechanically stimulated collagen gel longitudinal section after 14 days of culture. B . H&E of longitudinal section of static control. C . H&E of mechanically stimulated gel cross-section. D . H&E of static control cross-section.



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