Programmable mechanical stimulation influences tendon homeostasis in a bioreactor system

Abstract

Identification of functional programmable mechanical stimulation (PMS) on tendon not only provides the insight of the tendon homeostasis under physical/pathological condition, but also guides a better engineering strategy for tendon regeneration. The aims of the study are to design a bioreactor system with PMS to mimic the in vivo loading conditions, and to define the impact of different cyclic tensile strain on tendon. Rabbit Achilles tendons were loaded in the bioreactor with/without cyclic tensile loading (0.25 Hz for 8 h/day, 0-9% for 6 days). Tendons without loading lost its structure integrity as evidenced by disorientated collagen fiber, increased type III collagen expression, and increased cell apoptosis. Tendons with 3% of cyclic tensile loading had moderate matrix deterioration and elevated expression levels of MMP-1, 3, and 12, whilst exceeded loading regime of 9% caused massive rupture of collagen bundle. However, 6% of cyclic tensile strain was able to maintain the structural integrity and cellular function. Our data indicated that an optimal PMS is required to maintain the tendon homeostasis and there is only a narrow range of tensile strain that can induce the anabolic action. The clinical impact of this study is that optimized eccentric training program is needed to achieve maximum beneficial effects on chronic tendinopathy management.

Effect of mechanical stimulation on bone marrow stromal cell–seeded tendon slice constructs: A potential engineered tendon patch for rotator cuff repair

“…Bioreactors in tissue engineering [9] create a controlled and sterile environment for development of engineered tissues, including tendon [10]. Bioreactors designed to provide in vitro mechanical stimulation are thought to replicate physiologic conditions and promote cell differentiation and tenogenesis [11].…”

Finding the sweet spot via personalised Achilles tendon training: the future is within reach

“…Although further research is required to elucidate the specific loading conditions (ie, magnitude, duration, frequency and rate) that maximise tendon adaptation, in vitro 1 2 and in vivo 3–6 evidence indicates tendon has an optimal range or ‘sweet spot’7 within which mechanical loading promotes positive tissue adaptation or homeostasis, with either too much or too little loading being detrimental (figure 1). In vitro bioreactor studies of rabbit Achilles tendon have shown that continuous 8 hours/day for 6 days of 6% cyclic strain at 0.25 Hz maintains1 and promotes2 tendon health, but the same duration and frequency with strain magnitude of 3% and 9% disrupted the extracellular matrix. Tendons that were load-deprived for 12 days increased their expression of collagen of inferior material properties (ie, type III) and had diminished mechanical performance.…”

“…Although not represented in this figure, strain frequency, strain duration and strain rate also affect Achilles tendon adaptation. Figure adapted from Wang et al 1 and Pizzolato et al 7…”

Comparison of Clinical Efficacy Among Endoscopy-Assisted Radio-Frequency Ablation, Extracorporeal Shockwaves, and Eccentric Exercises in Treatment of Insertional Achilles Tendinosis

“…12 Eccentric exercises can reshape and enhance the tolerability of Achilles tendon by strengthening the fiber crosslink in the tendon. 13 A 5-year follow-up study 14 suggested that patients experienced a significant increase in the VISA-A scale scores after receiving eccentric exercises, whereas only a mild degree of pain remained. Another 5-year study 15 indicated that the overall efficacy rate was as high as 80%, whereas the recurrence rate was approximately 15%.…”