The beneficial effect of delayed compressive loading on tissue-engineered cartilage constructs cultured with TGF-beta3

Osteoarthritis Cartilage. 2007 Sep;15(9):1025-33. doi: 10.1016/j.joca.2007.03.008. Epub 2007 May 10.


Objective: To determine whether the functional properties of tissue-engineered constructs cultured in a chemically-defined medium supplemented briefly with TGF-beta3 can be enhanced with the application of dynamic deformational loading.

Methods: Primary immature bovine cells (2-3 months old) were encapsulated in agarose hydrogel (2%, 30 x 10(6)cells/ml) and cultured in chemically-defined medium supplemented for the first 2 weeks with transforming growth factor beta 3 (TGF-beta3) (10 microg/ml). Physiologic deformational loading (1 Hz, 3 h/day, 10% unconfined deformation initially and tapering to 2% peak-to-peak deformation by day 42) was applied either concurrent with or after the period of TGF-beta3 supplementation. Mechanical and biochemical properties were evaluated up to day 56.

Results: Dynamic deformational loading applied concurrently with TGF-beta3 supplementation yielded significantly lower (-90%) overall mechanical properties when compared to free-swelling controls. In contrast, the same loading protocol applied after the discontinuation of the growth factor resulted in significantly increased (+10%) overall mechanical properties relative to free-swelling controls. Equilibrium modulus values reach 1306+/-79 kPa and glycosaminoglycan levels reach 8.7+/-1.6% w.w. during this 8-week period and are similar to host cartilage properties (994+/-280 kPa, 6.3+/-0.9% w.w.).

Conclusions: An optimal strategy for the functional tissue engineering of articular cartilage, particularly to accelerate construct development, may incorporate sequential application of different growth factors and applied deformational loading.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cartilage, Articular / cytology*
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / physiology
  • Cattle
  • Cell Culture Techniques
  • Chondrocytes / cytology*
  • Chondrocytes / physiology
  • Collagen / analysis
  • Glycosaminoglycans / analysis
  • Models, Biological
  • Stress, Mechanical*
  • Tissue Engineering / methods*
  • Transforming Growth Factor beta3


  • Glycosaminoglycans
  • Transforming Growth Factor beta3
  • Collagen