Skip to main content
SpringerLink
Log in

Physical Stimulation of Chondrogenic Cells In Vitro: A Review

  • Symposium: Clinically Relevant Strategies for Treating Cartilage and Meniscal Pathology
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Mechanical stimuli are of crucial importance for the development and maintenance of articular cartilage. For conditioning of cartilaginous tissues, various bioreactor systems have been developed that have mainly aimed to produce cartilaginous grafts for tissue engineering applications. Emphasis has been on in vitro preconditioning, whereas the same devices could be used to attempt to predict the response of the cells in vivo or as a prescreening method before animal studies. As a result of the complexity of the load and motion patterns within an articulating joint, no bioreactor can completely recreate the in vivo situation.

Questions/purposes

This article aims to classify the various loading bioreactors into logical categories, highlight the response of mesenchymal stem cells and chondrocytes to the various stimuli applied, and determine which data could be used within a clinical setting.

Methods

We performed a Medline search using specific search terms, then selectively reviewed relevant research relating to physical stimulation of chondrogenic cells in vitro, focusing on cellular responses to the specific load applied.

Results

There is much data pertaining to increases in chondrogenic gene expression as a result of controlled loading protocols. Uniaxial loading leads to selective upregulation of genes normally associated with a chondrogenic phenotype, whereas multiaxial loading results in a broader pattern of chondrogenic gene upregulation. The potential for the body to be used as an in vivo bioreactor is being increasingly explored.

Conclusions

Bioreactors are important tools for understanding the potential response of chondrogenic cells within the joint environment. However, to replicate the natural in vivo situation, more complex motion patterns are required to induce more physiological chondrogenic gene upregulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A–C

Similar content being viewed by others

References

  1. Afoke NY, Byers PD, Hutton WC. Contact pressures in the human hip joint. J Bone Joint Surg Br. 1987;69:536–541.

    PubMed  CAS  Google Scholar 

  2. Angele P, Schumann D, Angele M, Kinner B, Englert C, Hente R, Fuchtmeier B, Nerlich M, Neumann C, Kujat R. Cyclic, mechanical compression enhances chondrogenesis of mesenchymal progenitor cells in tissue engineering scaffolds. Biorheology. 2004;41:335–346.

    PubMed  CAS  Google Scholar 

  3. Angele P, Yoo JU, Smith C, Mansour J, Jepsen KJ, Nerlich M, Johnstone B. Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J Orthop Res. 2003;21:451–457.

    Article  PubMed  CAS  Google Scholar 

  4. Appelman TP, Mizrahi J, Elisseeff JH, Seliktar D. The differential effect of scaffold composition and architecture on chondrocyte response to mechanical stimulation. Biomaterials. 2009;30:518–525.

    Article  PubMed  CAS  Google Scholar 

  5. Bartlett W, Gooding CR, Carrington RW, Skinner JA, Briggs TW, Bentley G. Autologous chondrocyte implantation at the knee using a bilayer collagen membrane with bone graft. A preliminary report. J Bone Joint Surg Br. 2005;87:330–332.

    Article  PubMed  CAS  Google Scholar 

  6. Behrens P, Bitter T, Kurz B, Russlies M. Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)—5-year follow-up. Knee. 2006;13:194–202.

    Article  PubMed  Google Scholar 

  7. Bosnakovski D, Mizuno M, Kim G, Takagi S, Okumura M, Fujinaga T. Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: influence of collagen type II extracellular matrix on MSC chondrogenesis. Biotechnol Bioeng. 2006;93:1152–1163.

    Article  PubMed  CAS  Google Scholar 

  8. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331:889–895.

    Article  PubMed  CAS  Google Scholar 

  9. Bryant SJ, Chowdhury TT, Lee DA, Bader DL, Anseth KS. Crosslinking density influences chondrocyte metabolism in dynamically loaded photocrosslinked poly(ethylene glycol) hydrogels. Ann Biomed Eng. 2004;32:407–417.

    Article  PubMed  Google Scholar 

  10. Buschmann MD, Gluzband YA, Grodzinsky AJ, Hunziker EB. Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J Cell Sci. 1995;108:1497–1508.

    PubMed  CAS  Google Scholar 

  11. Buschmann MD, Kim YJ, Wong M, Frank E, Hunziker EB, Grodzinsky AJ. Stimulation of aggrecan synthesis in cartilage explants by cyclic loading is localized to regions of high interstitial fluid flow. Arch Biochem Biophys. 1999;366:1–7.

    Article  PubMed  CAS  Google Scholar 

  12. Campbell JJ, Lee DA, Bader DL. Dynamic compressive strain influences chondrogenic gene expression in human mesenchymal stem cells. Biorheology. 2006;43:455–470.

    PubMed  Google Scholar 

  13. Candiani G, Raimondi MT, Aurora R, Lagana K, Dubini G. Chondrocyte response to high regimens of cyclic hydrostatic pressure in 3-dimensional engineered constructs. Int J Artif Organs. 2008;31:490–499.

    PubMed  CAS  Google Scholar 

  14. Candrian C, Vonwil D, Barbero A, Bonacina E, Miot S, Farhadi J, Wirz D, Dickinson S, Hollander A, Jakob M, Li Z, Alini M, Heberer M, Martin I. Engineered cartilage generated by nasal chondrocytes is responsive to physical forces resembling joint loading. Arthritis Rheum. 2008;58:197–208.

    Article  PubMed  CAS  Google Scholar 

  15. Carver SE, Heath CA. Increasing extracellular matrix production in regenerating cartilage with intermittent physiological pressure. Biotechnol Bioeng. 1999;62:166–174.

    Article  PubMed  CAS  Google Scholar 

  16. Caterson EJ, Nesti LJ, Li WJ, Danielson KG, Albert TJ, Vaccaro AR, Tuan RS. Three-dimensional cartilage formation by bone marrow-derived cells seeded in polylactide/alginate amalgam. J Biomed Mater Res. 2001;57:394–403.

    Article  PubMed  CAS  Google Scholar 

  17. Chowdhury TT, Bader DL, Shelton JC, Lee DA. Temporal regulation of chondrocyte metabolism in agarose constructs subjected to dynamic compression. Arch Biochem Biophys. 2003;417:105–111.

    Article  PubMed  CAS  Google Scholar 

  18. Connelly JT, Vanderploeg EJ, Levenston ME. The influence of cyclic tension amplitude on chondrocyte matrix synthesis: experimental and finite element analyses. Biorheology. 2004;41:377–387.

    PubMed  CAS  Google Scholar 

  19. Czichos H. Tribilogy: A Systems Approach to the Science and Technology of Friction, Lubrication, and Wear. Amsterdam: Elsevier; 1978.

    Google Scholar 

  20. Diduch DR, Jordan LC, Mierisch CM, Balian G. Marrow stromal cells embedded in alginate for repair of osteochondral defects. Arthroscopy. 2000;16:571–577.

    Article  PubMed  CAS  Google Scholar 

  21. Elder BD, Athanasiou KA. Synergistic and additive effects of hydrostatic pressure and growth factors on tissue formation. PLoS ONE. 2008;3:e2341.

    Article  PubMed  Google Scholar 

  22. Elder BD, Athanasiou KA. Hydrostatic pressure in articular cartilage tissue engineering: from chondrocytes to tissue regeneration. Tissue Eng Part B Rev. 2009;15:43–53.

    Article  PubMed  CAS  Google Scholar 

  23. Elder SH, Goldstein SA, Kimura JH, Soslowsky LJ, Spengler DM. Chondrocyte differentiation is modulated by frequency and duration of cyclic compressive loading. Ann Biomed Eng. 2001;29:476–482.

    Article  PubMed  CAS  Google Scholar 

  24. Fan JC, Waldman SD. The effect of intermittent static biaxial tensile strains on tissue engineered cartilage. Ann Biomed Eng. 2010;38:1672–1682.

    Article  PubMed  Google Scholar 

  25. Fitzgerald JB, Jin M, Grodzinsky AJ. Shear and compression differentially regulate clusters of functionally related temporal transcription patterns in cartilage tissue. J Biol Chem. 2006;281:24095–24103.

    Article  PubMed  CAS  Google Scholar 

  26. Frank EH, Jin M, Loening AM, Levenston ME, Grodzinsky AJ. A versatile shear and compression apparatus for mechanical stimulation of tissue culture explants. J Biomech. 2000;33:1523–1527.

    Article  PubMed  CAS  Google Scholar 

  27. Fukuda K, Asada S, Kumano F, Saitoh M, Otani K, Tanaka S. Cyclic tensile stretch on bovine articular chondrocytes inhibits protein kinase C activity. J Lab Clin Med. 1997;130:209–215.

    Article  PubMed  CAS  Google Scholar 

  28. Gavenis K, Kremer A, Von Walter M, Hollander DA, Schneider U, Schmidt-Rohlfing B. Effects of cyclic hydrostatic pressure on the metabolism of human osteoarthritic chondrocytes cultivated in a collagen gel. Artif Organs. 2007;31:91–98.

    Article  PubMed  CAS  Google Scholar 

  29. Geffre CP, Bliss CL, Szivek JA, DeYoung DW, Ruth JT, Margolis DS. Sensate scaffolds coupled to telemetry can monitor in vivo loading from within a joint over extended periods of time. J Biomed Mater Res B Appl Biomater. 2008;84:263–270.

    PubMed  Google Scholar 

  30. Gemmiti CV, Guldberg RE. Shear stress magnitude and duration modulates matrix composition and tensile mechanical properties in engineered cartilaginous tissue. Biotechnol Bioeng. 2009;104:809–820.

    PubMed  CAS  Google Scholar 

  31. Gooch KJ, Blunk T, Courter DL, Sieminski AL, Bursac PM, Vunjak-Novakovic G, Freed LE. IGF-I and mechanical environment interact to modulate engineered cartilage development. Biochem Biophys Res Commun. 2001;286:909–915.

    Article  PubMed  CAS  Google Scholar 

  32. Grad S, Gogolewski S, Alini M, Wimmer MA. Effects of simple and complex motion patterns on gene expression of chondrocytes seeded in 3D scaffolds. Tissue Eng. 2006;12:3171–3179.

    Article  PubMed  CAS  Google Scholar 

  33. Grad S, Lee CR, Wimmer MA, Alini M. Chondrocyte gene expression under applied surface motion. Biorheology. 2006;43:259–269.

    PubMed  Google Scholar 

  34. Haasper C, Zeichen J, Meister R, Krettek C, Jagodzinski M. Tissue engineering of osteochondral constructs in vitro using bioreactors. Injury. 2008;39(Suppl 1):S66–S76.

    Article  PubMed  Google Scholar 

  35. Hauselmann HJ, Aydelotte MB, Schumacher BL, Kuettner KE, Gitelis SH, Thonar EJ. Synthesis and turnover of proteoglycans by human and bovine adult articular chondrocytes cultured in alginate beads. Matrix. 1992;12:116–129.

    PubMed  CAS  Google Scholar 

  36. Heath CA, Magari SR. Mini-review: mechanical factors affecting cartilage regeneration in vitro. Biotechnol Bioeng. 1996;50:430–437.

    Article  PubMed  CAS  Google Scholar 

  37. Hosseini A, Van de Velde SK, Kozanek M, Gill TJ, Grodzinsky AJ, Rubash HE, Li G. In-vivo time-dependent articular cartilage contact behavior of the tibiofemoral joint. Osteoarthritis Cartilage. 2010;18:909–916.

    Article  PubMed  CAS  Google Scholar 

  38. Hu JC, Athanasiou KA. The effects of intermittent hydrostatic pressure on self-assembled articular cartilage constructs. Tissue Eng. 2006;12:1337–1344.

    Article  PubMed  CAS  Google Scholar 

  39. Huang CY, Hagar KL, Frost LE, Sun Y, Cheung HS. Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells. Stem Cells. 2004;22:313–323.

    Article  PubMed  CAS  Google Scholar 

  40. Huang CY, Reuben PM, Cheung HS. Temporal expression patterns and corresponding protein inductions of early responsive genes in rabbit bone marrow-derived mesenchymal stem cells under cyclic compressive loading. Stem Cells. 2005;23:1113–1121.

    Article  PubMed  CAS  Google Scholar 

  41. Huang CY, Reuben PM, D’Ippolito G, Schiller PC, Cheung HS. Chondrogenesis of human bone marrow-derived mesenchymal stem cells in agarose culture. Anat Rec A Discov Mol Cell Evol Biol. 2004;278:428–436.

    Article  PubMed  Google Scholar 

  42. Jin M, Emkey GR, Siparsky P, Trippel SB, Grodzinsky AJ. Combined effects of dynamic tissue shear deformation and insulin-like growth factor I on chondrocyte biosynthesis in cartilage explants. Arch Biochem Biophys. 2003;414:223–231.

    Article  PubMed  CAS  Google Scholar 

  43. Jin M, Frank EH, Quinn TM, Hunziker EB, Grodzinsky AJ. Tissue shear deformation stimulates proteoglycan and protein biosynthesis in bovine cartilage explants. Arch Biochem Biophys. 2001;395:41–48.

    Article  PubMed  CAS  Google Scholar 

  44. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res. 1998;238:265–272.

    Article  PubMed  CAS  Google Scholar 

  45. Jung Y, Kim SH, Kim SH, Kim YH, Xie J, Matsuda T, Min BG. Cartilaginous tissue formation using a mechano-active scaffold and dynamic compressive stimulation. J Biomater Sci Polym Ed. 2008;19:61–74.

    Article  PubMed  CAS  Google Scholar 

  46. Kelly DJ, Prendergast PJ. Mechano-regulation of stem cell differentiation and tissue regeneration in osteochondral defects. J Biomech. 2005;38:1413–1422.

    Article  PubMed  CAS  Google Scholar 

  47. Kisiday JD, Jin M, DiMicco MA, Kurz B, Grodzinsky AJ. Effects of dynamic compressive loading on chondrocyte biosynthesis in self-assembling peptide scaffolds. J Biomech. 2004;37:595–604.

    Article  PubMed  Google Scholar 

  48. Kisiday JD, Kopesky PW, Evans CH, Grodzinsky AJ, McIlwraith CW, Frisbie DD. Evaluation of adult equine bone marrow- and adipose-derived progenitor cell chondrogenesis in hydrogel cultures. J Orthop Res. 2008;26:322–331.

    Article  PubMed  CAS  Google Scholar 

  49. Klein TJ, Malda J, Sah RL, Hutmacher DW. Tissue engineering of articular cartilage with biomimetic zones. Tissue Eng Part B Rev. 2009;15:143–157.

    Article  PubMed  CAS  Google Scholar 

  50. Kozanek M, Hosseini A, Liu F, Van de Velde SK, Gill TJ, Rubash HE, Li G. Tibiofemoral kinematics and condylar motion during the stance phase of gait. J Biomech. 2009;42:1877–1884.

    Article  PubMed  Google Scholar 

  51. Kupcsik L, Stoddart MJ, Li Z, Benneker LM, Alini M. Improving chondrogenesis—potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering. Tissue Eng Part A. 2010;16:1845–1855.

    Article  PubMed  CAS  Google Scholar 

  52. Lacroix D, Prendergast PJ. A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J Biomech. 2002;35:1163–1171.

    Article  PubMed  CAS  Google Scholar 

  53. Lacroix D, Prendergast PJ, Li G, Marsh D. Biomechanical model to simulate tissue differentiation and bone regeneration: application to fracture healing. Med Biol Eng Comput. 2002;40:14–21.

    Article  PubMed  CAS  Google Scholar 

  54. Lee CR, Grad S, Gorna K, Gogolewski S, Goessl A, Alini M. Fibrin-polyurethane composites for articular cartilage tissue engineering: a preliminary analysis. Tissue Eng. 2005;11:1562–1573.

    Article  PubMed  CAS  Google Scholar 

  55. Li Z, Kupcsik L, Yao S, Alini M, Stoddart MJ. Chondrogenesis of human bone marrow mesenchymal stem cells in fibrin-polyurethane composites. Tissue Eng Part A. 2009;15:1729–1737.

    Article  PubMed  CAS  Google Scholar 

  56. Li Z, Kupcsik L, Yao SJ, Alini M, Stoddart MJ. Mechanical load modulates chondrogenesis of human mesenchymal stem cells through the TGF-beta pathway. J Cell Mol Med. 2010;14:1338–1346.

    Article  PubMed  CAS  Google Scholar 

  57. Li Z, Yao S, Alini M, Grad S. Different response of articular chondrocyte subpopulations to surface motion. Osteoarthritis Cartilage. 2007;15:1034–1041.

    Article  PubMed  CAS  Google Scholar 

  58. Li Z, Yao SJ, Alini M, Stoddart MJ. Chondrogenesis of human bone marrow mesenchymal stem cells in fibrin-polyurethane composites is modulated by frequency and amplitude of dynamic compression and shear stress. Tissue Eng Part A. 2010;16:575–584.

    Article  PubMed  CAS  Google Scholar 

  59. Lu Y, Dhanaraj S, Wang Z, Bradley DM, Bowman SM, Cole BJ, Binette F. Minced cartilage without cell culture serves as an effective intraoperative cell source for cartilage repair. J Orthop Res. 2006;24:1261–1270.

    Article  PubMed  Google Scholar 

  60. Luo ZJ, Seedhom BB. Light and low-frequency pulsatile hydrostatic pressure enhances extracellular matrix formation by bone marrow mesenchymal cells: an in-vitro study with special reference to cartilage repair. Proc Inst Mech Eng H. 2007;221:499–507.

    PubMed  CAS  Google Scholar 

  61. Ma HL, Hung SC, Lin SY, Chen YL, Lo WH. Chondrogenesis of human mesenchymal stem cells encapsulated in alginate beads. J Biomed Mater Res A. 2003;64:273–281.

    Article  PubMed  Google Scholar 

  62. Mauck RL, Nicoll SB, Seyhan SL, Ateshian GA, Hung CT. Synergistic action of growth factors and dynamic loading for articular cartilage tissue engineering. Tissue Eng. 2003;9:597–611.

    Article  PubMed  CAS  Google Scholar 

  63. Mauck RL, Soltz MA, Wang CC, Wong DD, Chao PH, Valhmu WB, Hung CT, Ateshian GA. Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng. 2000;122:252–260.

    Article  PubMed  CAS  Google Scholar 

  64. Mauck RL, Wang CC, Oswald ES, Ateshian GA, Hung CT. The role of cell seeding density and nutrient supply for articular cartilage tissue engineering with deformational loading. Osteoarthritis Cartilage. 2003;11:879–890.

    Article  PubMed  CAS  Google Scholar 

  65. Meinel L, Hofmann S, Karageorgiou V, Zichner L, Langer R, Kaplan D, Vunjak-Novakovic G. Engineering cartilage-like tissue using human mesenchymal stem cells and silk protein scaffolds. Biotechnol Bioeng. 2004;88:379–391.

    Article  PubMed  CAS  Google Scholar 

  66. Miyanishi K, Trindade MC, Lindsey DP, Beaupre GS, Carter DR, Goodman SB, Schurman DJ, Smith RL. Dose- and time-dependent effects of cyclic hydrostatic pressure on transforming growth factor-beta3-induced chondrogenesis by adult human mesenchymal stem cells in vitro. Tissue Eng. 2006;12:2253–2262.

    Article  PubMed  CAS  Google Scholar 

  67. Miyanishi K, Trindade MC, Lindsey DP, Beaupre GS, Carter DR, Goodman SB, Schurman DJ, Smith RL. Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro. Tissue Eng. 2006;12:1419–1428.

    Article  PubMed  CAS  Google Scholar 

  68. Mizuno S, Tateishi T, Ushida T, Glowacki J. Hydrostatic fluid pressure enhances matrix synthesis and accumulation by bovine chondrocytes in three-dimensional culture. J Cell Physiol. 2002;193:319–327.

    Article  PubMed  CAS  Google Scholar 

  69. Mouw JK, Connelly JT, Wilson CG, Michael KE, Levenston ME. Dynamic compression regulates the expression and synthesis of chondrocyte-specific matrix molecules in bone marrow stromal cells. Stem Cells. 2007;25:655–663.

    Article  PubMed  CAS  Google Scholar 

  70. Mow VC, Wang CC. Some bioengineering considerations for tissue engineering of articular cartilage. Clin Orthop Relat Res. 1999;367(Suppl):S204–S223.

    Article  PubMed  Google Scholar 

  71. Nakamura S, Arai Y, Takahashi KA, Terauchi R, Ohashi S, Mazda O, Imanishi J, Inoue A, Tonomura H, Kubo T. Hydrostatic pressure induces apoptosis of chondrocytes cultured in alginate beads. J Orthop Res. 2006;24:733–739.

    Article  PubMed  CAS  Google Scholar 

  72. Nicodemus GD, Bryant SJ. The role of hydrogel structure and dynamic loading on chondrocyte gene expression and matrix formation. J Biomech. 2008;41:1528–1536.

    Article  PubMed  CAS  Google Scholar 

  73. Nugent-Derfus GE, Takara T, O’Neill JK, Cahill SB, Gortz S, Pong T, Inoue H, Aneloski NM, Wang WW, Vega KI, Klein TJ, Hsieh-Bonassera ND, Bae WC, Burke JD, Bugbee WD, Sah RL. Continuous passive motion applied to whole joints stimulates chondrocyte biosynthesis of PRG4. Osteoarthritis Cartilage. 2007;15:566–574.

    Article  PubMed  CAS  Google Scholar 

  74. Paige KT, Vacanti CA. Engineering new tissue: formation of neo-cartilage. Tissue Engineering. 1995;1:97–107.

    Article  PubMed  CAS  Google Scholar 

  75. Parkkinen JJ, Ikonen J, Lammi MJ, Laakkonen J, Tammi M, Helminen HJ. Effects of cyclic hydrostatic pressure on proteoglycan synthesis in cultured chondrocytes and articular cartilage explants. Arch Biochem Biophys. 1993;300:458–465.

    Article  PubMed  CAS  Google Scholar 

  76. Pelaez D, Huang CY, Cheung HS. Cyclic compression maintains viability and induces chondrogenesis of human mesenchymal stem cells in fibrin gel scaffolds. Stem Cells Dev. 2009;18:93–102.

    Article  PubMed  CAS  Google Scholar 

  77. Prendergast PJ, Huiskes R, Soballe K. ESB Research Award 1996. Biophysical stimuli on cells during tissue differentiation at implant interfaces. J Biomech. 1997;30:539–548.

    Article  PubMed  CAS  Google Scholar 

  78. Sah RL, Kim YJ, Doong JY, Grodzinsky AJ, Plaas AH, Sandy JD. Biosynthetic response of cartilage explants to dynamic compression. J Orthop Res. 1989;7:619–636.

    Article  PubMed  CAS  Google Scholar 

  79. Salzmann GM, Nuernberger B, Schmitz P, Anton M, Stoddart MJ, Grad S, Milz S, Tischer T, Vogt S, Gansbacher B, Imhoff AB, Alini M. Physicobiochemical synergism through gene therapy and functional tissue engineering for in vitro chondrogenesis. Tissue Eng Part A. 2009;15:2513–2524.

    Article  PubMed  CAS  Google Scholar 

  80. Schumann D, Kujat R, Nerlich M, Angele P. Mechanobiological conditioning of stem cells for cartilage tissue engineering. Biomed Mater Eng. 2006;16:S37–S52.

    PubMed  CAS  Google Scholar 

  81. Solchaga LA, Dennis JE, Goldberg VM, Caplan AI. Hyaluronic acid-based polymers as cell carriers for tissue-engineered repair of bone and cartilage. J Orthop Res. 1999;17:205–213.

    Article  PubMed  CAS  Google Scholar 

  82. Steinert A, Weber M, Dimmler A, Julius C, Schutze N, Noth U, Cramer H, Eulert J, Zimmermann U, Hendrich C. Chondrogenic differentiation of mesenchymal progenitor cells encapsulated in ultrahigh-viscosity alginate. J Orthop Res. 2003;21:1090–1097.

    Article  PubMed  CAS  Google Scholar 

  83. Stevens MM, Marini RP, Schaefer D, Aronson J, Langer R, Shastri VP. In vivo engineering of organs: the bone bioreactor. Proc Natl Acad Sci USA. 2005;102:11450–11455.

    Article  PubMed  CAS  Google Scholar 

  84. Stoddart MJ, Ettinger L, Hauselmann HJ. Enhanced matrix synthesis in de novo, scaffold free cartilage-like tissue subjected to compression and shear. Biotechnol Bioeng. 2006;95:1043–1051.

    Article  PubMed  CAS  Google Scholar 

  85. Takahashi I, Nuckolls GH, Takahashi K, Tanaka O, Semba I, Dashner R, Shum L, Slavkin HC. Compressive force promotes sox9, type II collagen and aggrecan and inhibits IL-1beta expression resulting in chondrogenesis in mouse embryonic limb bud mesenchymal cells. J Cell Sci. 1998;111:2067–2076.

    PubMed  CAS  Google Scholar 

  86. Terraciano V, Hwang N, Moroni L, Park HB, Zhang Z, Mizrahi J, Seliktar D, Elisseeff J. Differential response of adult and embryonic mesenchymal progenitor cells to mechanical compression in hydrogels. Stem Cells. 2007;25:2730–2738.

    Article  PubMed  CAS  Google Scholar 

  87. Toyoda T, Seedhom BB, Yao JQ, Kirkham J, Brookes S, Bonass WA. Hydrostatic pressure modulates proteoglycan metabolism in chondrocytes seeded in agarose. Arthritis Rheum. 2003;48:2865–2872.

    Article  PubMed  CAS  Google Scholar 

  88. Villanueva I, Weigel CA, Bryant SJ. Cell-matrix interactions and dynamic mechanical loading influence chondrocyte gene expression and bioactivity in PEG-RGD hydrogels. Acta Biomater. 2009;5:2832–2846.

    Article  PubMed  CAS  Google Scholar 

  89. von Eisenhart R, Adam C, Steinlechner M, Muller-Gerbl M, Eckstein F. Quantitative determination of joint incongruity and pressure distribution during simulated gait and cartilage thickness in the human hip joint. J Orthop Res. 1999;17:532–539.

    Article  Google Scholar 

  90. Wagner DR, Lindsey DP, Li KW, Tummala P, Chandran SE, Smith RL, Longaker MT, Carter DR, Beaupre GS. Hydrostatic pressure enhances chondrogenic differentiation of human bone marrow stromal cells in osteochondrogenic medium. Ann Biomed Eng. 2008;36:813–820.

    Article  PubMed  Google Scholar 

  91. Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002;10:199–206.

    Article  PubMed  CAS  Google Scholar 

  92. Waldman SD, Couto DC, Grynpas MD, Pilliar RM, Kandel RA. Multi-axial mechanical stimulation of tissue engineered cartilage: review. Eur Cell Mater. 2007;13:66–73.

    PubMed  CAS  Google Scholar 

  93. Wang PY, Chow HH, Lai JY, Liu HL, Tsai WB. Dynamic compression modulates chondrocyte proliferation and matrix biosynthesis in chitosan/gelatin scaffolds. J Biomed Mater Res B Appl Biomater. 2009;91:143–152.

    PubMed  Google Scholar 

  94. Wayne JS, McDowell CL, Shields KJ, Tuan RS. In vivo response of polylactic acid-alginate scaffolds and bone marrow-derived cells for cartilage tissue engineering. Tissue Eng. 2005;11:953–963.

    Article  PubMed  CAS  Google Scholar 

  95. Wenger R, Hans MG, Welter JF, Solchaga LA, Sheu YR, Malemud CJ. Hydrostatic pressure increases apoptosis in cartilage-constructs produced from human osteoarthritic chondrocytes. Front Biosci. 2006;11:1690–1695.

    Article  PubMed  CAS  Google Scholar 

  96. Wernike E, Li Z, Alini M, Grad S. Effect of reduced oxygen tension and long-term mechanical stimulation on chondrocyte-polymer constructs. Cell Tissue Res. 2008;331:473–483.

    Article  PubMed  CAS  Google Scholar 

  97. Wimmer MA, Alini M, Grad S. The effect of sliding velocity on chondrocytes activity in 3D scaffolds. J Biomech. 2009;42:424–429.

    Article  PubMed  Google Scholar 

  98. Wimmer MA, Grad S, Kaup T, Hanni M, Schneider E, Gogolewski S, Alini M. Tribology approach to the engineering and study of articular cartilage. Tissue Eng. 2004;10:1436–1445.

    PubMed  CAS  Google Scholar 

  99. Wong M, Siegrist M, Goodwin K. Cyclic tensile strain and cyclic hydrostatic pressure differentially regulate expression of hypertrophic markers in primary chondrocytes. Bone. 2003;33:685–693.

    Article  PubMed  CAS  Google Scholar 

  100. Xie F, Weiss P, Chauvet O, Le Bideau J, Tassin JF. Kinetic studies of a composite carbon nanotube-hydrogel for tissue engineering by rheological methods. J Mater Sci Mater Med. 2010;21:1163–1168.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos Platz, Switzerland

    Sibylle Grad PhD, David Eglin PhD, Mauro Alini PhD & Martin J. Stoddart PhD

Authors
  1. Sibylle Grad PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Eglin PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mauro Alini PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin J. Stoddart PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin J. Stoddart PhD.

Additional information

Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

About this article

Cite this article

Grad, S., Eglin, D., Alini, M. et al. Physical Stimulation of Chondrogenic Cells In Vitro: A Review. Clin Orthop Relat Res 469, 2764–2772 (2011). https://doi.org/10.1007/s11999-011-1819-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11999-011-1819-9

Keywords

Search

Navigation