Relative contributions of mechanical degradation, enzymatic degradation, and repair of the extracellular matrix on the response of tendons when subjected to under‐ and over‐ mechanical stimulations in vitro

Abstract

Tendon response to mechanical loading results in either homeostasis, improvement, or degeneration of tissue condition. In an effort to better understand the development of tendinopathies, this study investigated the mechanical and structural responses of tendons subjected to under-and over-stimulations (1.2% and 1.8% strain respectively, 1 Hz). The objective was to examine three sub-processes of tendon response: mechanical degradation, enzymatic degradation, and repair of the extracellular matrix. We subjected rat tail tendons to a 10-day stimulation protocol with four periods of 6 h each day: 30 min of stimulation and 5 h 30 min of rest. To investigate the contribution of the three sub-processes, we controlled the contribution of the cells through variations in the nutrient and protease inhibitor content in the in vitro solutions. Using nondestructive cyclic tests, we evaluated the daily changes in the peak stress. To assess structural changes, we carried out microscopic analyses at the end of the study period. We observed that the relative contributions of the sub-processes differed according to the stimulation amplitude. With over-stimulation of tendons immersed in DMEM, we succeeded in reducing enzymatic degradation and increasing peak stress. In under-stimulation, the addition of protease inhibitors was required to obtain the same result. ß

Three-Dimensional-Construct Bioreactor Conditioning in Human Tendon Tissue Engineering

“…35 Cousineau-Pelletier and Langelier demonstrated that using stimulation of intermediate amplitude (avoiding over-and under-stimulation), degradation can be minimized. 36 While our findings suggest a weak dose-response relationship between load magnitude and mechanical properties, this did not reach statistical significance, suggesting that load magnitude may be less important than the conditioning duration. Conditioning at higher load magnitudes (e.g., 5 N and 10 N per TEC segment) was not possible because of motor overheating.…”

Low Stress Tendon Fatigue is a Relatively Rapid Process in the Context of Overuse Injuries

“…Moreover, the shape and dimensions of the curve will vary with the addition of cellular activity (the processes of repair and enzymatic degradation) which the authors will try to evaluate in future studies just as has been done with strain-controlled stimulation. 9 Those studies will be more complex and will require more advanced modeling techniques, because other variables such as the incorporation of rest time will eventually need to be included. FIGURE 9.…”

“…The efficiency of this method was noticed in a study conducted by the authors' group on live tissues under very low amplitude mechanical stimulation. 9 The second factor is contamination which was avoided by using good practices in tissue culture as well as antibiotics/antimycotics. The final factor is time which can modify the tissue via thermodynamics.…”

Repopulation of Intrasynovial Flexor Tendon Allograft with Bone Marrow Stromal Cells: AnEx VivoModel

“…This would be a necessary analysis in a future in vivo study, to assess the effect of cellularity on graft degradation and remodeling. 57 In conclusion, making multiple short slits in an intrasynovial tendon decellularized for potential allograft use enhances the penetration and survival of seeded cells. The process does not change the tendon's tensile stiffness.…”