The Effect of Intermittent Static Biaxial Tensile Strains on Tissue Engineered Cartilage

Abstract

Mechanical stimulation of engineered cartilage constructs is a commonly applied method used to accelerate tissue formation and improve the mechanical properties of the developed tissue. While the effects of compression and shear have been widely studied, the effect of tension has received relatively little attention. As articular cartilage in vivo is subjected to a degree of static tension (pre-tension) even in the absence of externally applied loads, the purpose of this study was to investigate the effect of intermittent static biaxial tensile strains (BTS) on chondrocyte metabolism and resultant tissue formation. Using a custom-design loading fixture to apply BTS, the optimal conditions for stimulating extracellular matrix synthesis were under average magnitudes of 3.8% radial and 2.1% circumferential tensile strains for 30 min. Tissue constructs subjected to tensile strain stimulation 3 times/week for a period of 4 weeks displayed increased thickness (35 +/- 18%) and proteoglycan content (22 +/- 7%) without an associated change in mechanical properties. In contrast, constructs stimulated daily over the same time period exhibited negligible effects in terms of ECM accumulation suggesting that the frequency of stimulation needs to be precisely controlled. The results of this study demonstrate that while tension can be used as potential biomechanical stimulus to improve tissue formation, further optimization of this process needs to be conducted to improve ECM accumulation and tissue mechanical properties after long-term exposure to tensile stimuli.

Effects of Perfusion and Dynamic Loading on Human Neocartilage Formation in Alginate Hydrogels

“…Intermittent loading regimes have significant effect on ECM production. 41,50 In particular, Nicodemus and Bryant 41 showed that loading and the timing of when loading is applied can dramatically influence the anabolic and catabolic activities of chondrocytes in polyethylene glycol gels. A delayed loading regime has less effect on stimulating anabolic and catabolic gene expression in comparison to using an immediate application of an intermittent loading regime.…”

Physical Stimulation of Chondrogenic Cells In Vitro: A Review

“…On the other hand, it was suggested cyclic tension activates the hypertrophic pathway and increases the expression of markers typically associated with chondrocytes undergoing terminal differentiation to hypertrophic chondrocytes (eg, collagen X) [99]. Because there is evidence that articular cartilage in vivo is under a degree of static pretension, the effect of intermittent static biaxial tensile strains on cartilaginous constructs was studied [24]. Average magnitudes of 3.8% radial and 2.1% circumferential tensile strains for 30 minutes were identified as leading to the greatest increase in proteoglycan content.…”

An integrated instrument for rapidly deforming living cells using rapid pressure pulses and simultaneously monitoring applied strain in near real time

“…For instance, the mechanical compression of primary chondrocytes affects ATP release, 3 ion channel formation, 4 activates transcription factors such as NF Kβ 5 and can activate kinases such as MAP kinase, 6 focal adhesion kinase, 7 and ERK, 8 as well as Interleukin-1 signaling. 9 More long term, mechanical loading can also alter the expression of collagen [10][11][12][13][14][15][16] and enzymes 7,17 involved in tissue remodeling. Typical frequencies encountered in cell loading in these cases are on the order of 1-10 Hz.…”