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X-ray of a typical diarthrodial joint with inset highlighting the pronounced anisotropic architecture of the articular layer.
McKay Orthopaedic Research Laboratory > Mauck Lab > Bioreactor Development for Articular Cartilage Tissue Engineering

Bioreactor Development for Articular Cartilage Tissue Engineering

Recent cartilage tissue engineering endeavors have centered on the idea of "functional tissue engineering (FTE)". This subset of tissue engineering utilizes bioreactors that recreate a physiologic loading environment to foster construct growth [3,6]. These studies have focused on the use of a particular mechanical signal applied in isolation [4,5,8-10,12], such as axial compression or hydrostatic pressurization. The natural loading environment in diarthrodial joints is more complex, however, and changes with developmental stage. With postnatal joint loading, opposing cartilage surfaces come in contact and move relative to one another, generating simultaneous tensile and compressive forces along a moving point of contact, with fluid pressurization beneath the point of contact and fluid flow at the peripheries [13]. With development and use, an isotropic cartilaginous assembly is reformed into a terminally differentiated tissue exhibiting significant anisotropy along preferred directions [1,2,14] which in turn influences the functional response of the tissue [7,11]. Tissue anisotropy is thus a critical component of the functional properties of the native tissue, and must therefore be a parameter to consider when engineering tissue replacements. To address this issue, a novel sliding contact bioreactor is under development to test the hypothesis that the long-term application of physiologic sliding contact will increase the compressive and tensile (in the direction of sliding) mechanical properties of MSC- and chondrocyte-laden hydrogel constructs. It is hypothesized that these constructs will exhibit an enhanced collagen content as well as a parallel collagen fiber orientation in the direction of loading and may exhibit prolonged durability in the native joint loading environment.


Schematic of novel sliding contact bioreactor.

References
  1. Archer CW, Dowthwaite GP, Francis-West PH, 2003, "Development of synovial joints," Birth Def Res (Part C), 69: 144-55.
  2. Below S, Arnoczky SP, Dodds J, Kooima C, Walter N, 2002, "The split-line pattern of the distal femur: a consideration in the orientation of autologous cartilage grafts," J Arthros Rel Surg, 18: 613-17.
  3. Butler DL, Goldstein SA, Guilak F, 2000, "Functional tissue engineering: the role of biomechanics," J Biomech Eng, 122: 570-5.
  4. Carver SE, Heath CA, 1999, "Increasing extracellular matrix production in regenerating cartilage with intermittent physiological pressure," Biotechnol Bioeng, 62: 166-74.
  5. Carver SE, Heath CA, 1999, "Influence of intermittent pressure, fluid flow, and mixing on the regenerative properties of articular chondrocytes," Biotechnol Bioeng, 65: 274-81.
  6. Guilak F, Butler DL, Goldstein SA, 2001, "Functional tissue engineering: the role of biomechanics in articular cartilage repair," Clin Orthop, S295-305.
  7. Krishnan R, Kopacz M, Ateshian GA, 2004, "Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication," J Orthop Res, 22: 565-70.
  8. Mauck RL, Nicoll SB, Seyhan SL, Ateshian GA, Hung CT, 2003, "Synergistic action of growth factors and dynamic loading for articular cartilage tissue engineering," Tissue Eng, 9: 597-611.
  9. Mauck RL, Soltz MA, Wang CC, Wong DD, Chao PH, Valhmu WB, Hung CT, Ateshian GA, 2000, "Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels," J Biomech Eng, 122: 252-60.
  10. Mauck RL, Wang CC, Oswald ES, Ateshian GA, Hung CT, 2003, "The role of cell seeding density and nutrient supply for articular cartilage tissue engineering with deformational loading," Osteoarthritis Cartilage, 11: 879-90.
  11. Soltz MA, Ateshian GA, 2000, "A Conewise Linear Elasticity mixture model for the analysis of tension-compression nonlinearity in articular cartilage," J Biomech Eng, 122: 576-86.
  12. Waldman SD, Spiteri CG, Grynpas MD, Pilliar RM, Kandel RA, 2003, "Long-term intermittent shear deformation imporves the quality of cartilaginous tissue formed in vitro," J Orthop Res, 21: 590-6.
  13. Wang H, Ateshian GA, 1997, "The normal stress effect and equilibrium friction coefficient of articular cartilage under steady frictional shear," J Biomech, 30: 771-6.
  14. Williamson AK, Chen AC, Sah RL, 2001, "Compressive properties and function-composition relationships of developing bovine articular cartilage," J Orthop Res, 19: 1113-21.

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