Early-stage calcification promotes tendon damage under cyclic loading through alterations in interfascicular matrix viscoelastic properties.

Abstract

Calcification is a prevalent condition that alters mechanical and structural properties of soft tissues. While significant efforts have been devoted to the characterization of tendon mechanics, little work has been done so far on understanding the impact of calcification on tissues such as tendons. In this work, we investigate the influence of cycling loading and forced fluid flow on the mechanical and structural properties of tendon fascicle bundles of varying interfascicular matrix (IFM) content at an early stage of calcification. The calcification process was modeled using sample incubation in concentrated simulated body fluid. To evaluate the biomechanical responses of the tendon over the course of calcification, we compared four sets of samples incubated for 7 days in simulated body fluid, forced fluid flow and under cyclic uniaxial loading against a non-incubated control. Mechanical and structural properties were investigated using uniaxial tests, scanning electron microscopy and inductively coupled plasma optical emission spectroscopy. The study revealed that the initial phase of calcification causes an increase in the elasticity, as well as a drop in the normalized value of hysteresis for both IFM-rich and IFM-poor regions of the tendon. However, the relaxation behavior of the tissue remained unchanged during calcification proving that calcium phosphate deposits do not affect the IFM viscoplastic behavior but tissue viscoelasticity instead, which is manifested by a change in hysteresis. The greatest changes in stiffness are observed for statically incubated samples, while cyclically loaded samples were the most susceptible to fibril damage although they did not demonstrate the greatest increases in elastic modulus. The results presented in this work show that the calcification process modifies the collagen-matrix interactions, which leads to a change in their mechanical properties depending on the loading conditions. These findings contribute to our understanding of the pathogenesis of tendinopathy and have the potential to assist in the identification of effective treatment strategies for calcification-induced disorders.