Abstract
Mechano-regulation during tendon healing, i.e. the relationship between mechanical stimuli and cellular response, has received more attention recently. However, the basic mechanobiological mechanisms governing tendon healing after a rupture are still not well-understood. Literature has reported spatial and temporal variations in the healing of ruptured tendon tissue. In this study, we explored a computational modeling approach to describe tendon healing. In particular, a novel 3D mechano-regulatory framework was developed to investigate spatio-temporal evolution of collagen content and orientation, and temporal evolution of tendon stiffness during early tendon healing. Based on an extensive literature search, two possible relationships were proposed to connect levels of mechanical stimuli to collagen production. Since literature remains unclear on strain-dependent collagen production at high levels of strain, the two investigated production laws explored the presence or absence of collagen production upon non-physiologically high levels of strain (>15%). Implementation in a finite element framework, pointed to large spatial variations in strain magnitudes within the callus tissue, which resulted in predictions of distinct spatial distributions of collagen over time. The simulations showed that the magnitude of strain was highest in the tendon core along the central axis, and decreased towards the outer periphery. Consequently, decreased levels of collagen production for high levels of tensile strain were shown to accurately predict the experimentally observed delayed collagen production in the tendon core. In addition, our healing framework predicted evolution of collagen orientation towards alignment with the tendon axis and the overall predicted tendon stiffness agreed well with experimental data. In this study, we explored the capability of a numerical model to describe spatial and temporal variations in tendon healing and we identified that understanding mechano-regulated collagen production can play a key role in explaining heterogeneities observed during tendon healing.
Highlights
The biomechanical function of tendons is primarily a result of its unique tissue composition, organization and mechanical properties
There is no consensus on the optimal treatment since the effect of loading on Achilles tendon healing is not fully understood
We observed that strain-dependent tissue formation could explain recent observations of decreased tissue formation in the core of the healing callus during early tendon healing
Summary
The biomechanical function of tendons is primarily a result of its unique tissue composition, organization and mechanical properties. Tendon healing is initiated with an acute inflammatory stage, which is followed by production and alignment of extracellular matrix (ECM; Collagen type-I and III) to restore the loadbearing capacity. Studies that investigated collagen formation and orientation during Achilles tendon healing described an increasing alignment of collagen with time in rats [3] and rabbits [4,5]. It is widely accepted that mechanical loading affects tendon healing. Numerous experimental studies have investigated the temporal changes in collagen content, collagen organization and mechanical properties during tendon healing comparing how different degrees of mechanical loading affect tendon healing [6,7,8,9,10]. Extensive experimental data describing the spatio-temporal evolution of collagen properties (e.g. content and orientation) in the callus during tendon healing has been limited
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