Community Research and Development Information Service - CORDIS

FP7

TENDON_MECHBIO Report Summary

Project ID: 626941
Funded under: FP7-PEOPLE
Country: Sweden

Final Report Summary - TENDON_MECHBIO (Biomechanics and mechanobiology of the Achilles tendon)

The Achilles tendon is the largest tendon in the human body and the most frequently injured. Inappropriate and repetitive external loading of the tendon is believed to result in tendinopathy, which is chronic tendon injury that is inflammatory and can lead to complete ruptures. There is no well-founded evidence on how to best treat tendon injuries and healing times are very long. Nearly 30% of all orthopaedic consultations are tendon related, making tendon injuries very costly for the society in terms of exceeded health costs and loss in workforce. Therefore, better basic understanding of the synergies between loading and tendon health and restoration is necessary.

Tendons are hierarchical tissues that consist primarily of water (70%). The remaining 30% of the tissue is composed of mainly collagen, which provides the tendon its mechanical strength in tension. The collagen molecule is packed in fascicles and forms fibrils that are further packed in so called collagen fibres. These fibrils and fibres reside in a tissue matrix that is rich in proteoglycan and contains tendon cells. Proteoglycan is a hydrophilic molecule that binds water and enables interfibrillar sliding. The cells that reside in this space sense this sliding and fluid movement as biophysical stimuli and can alter their biological response thereafter by synthesizing matrix molecules. Studies on repairing tendons have shown that both over- and under-stimulation of injured tendons can lead to degeneration instead of healing, whereas a “correct” loading can be beneficial for the repair process. This magnitude of loading is yet unknown due to the complex biology of the tendon, which leaves existing therapies of complete ruptures controversial.

This project has combined computational and experimental approaches to investigate how mechanical loading affects tendon health and repair. Specific aims:
Aim 1: Investigate the multistructural biomechanical behavior of the intact Achilles tendon with a poroviscoelastic fibre-reinforced material model
Aim 2: Explore the long-term mechanobiological effects on the biomechanical properties of Achilles tendon under healing

An existing material model for articular cartilage was modified to instead capture the mechanical behavior of Achilles tendons. This model was poroviscoelastic fibre-reinforced, which means that the tissue was modelled as biphasic (consisting of a solid and a fluid phase). The fluid phase was modelled as water and the solid phase was divided into a fibre part, representing the collagen, and a non-fibrillar part which was the proteoglycan-rich matrix. The collagen fibres were assumed to be aligned parallel as in healthy Achilles tendons. The unknown model parameters were optimized in a computational scheme against experimental data of rat Achilles tendons, provided by collaborators. This study concluded that this adapted material model could nicely capture the behavior of rat Achilles tendons during cyclic tensile loading. However, it was limited in describing the fluid exudation of the tendon during tension.

The material model for tendons was further modified to be able to consider the interstitial fluid behavior. The previously isotropic non-fibrillar matrix was updated to a transversely isotropic matrix. This new model was optimized against the same experimental data as in the previous study and the model was performing equally well on macroscopic tendon behavior but could also capture a more accurate fluid behavior. Both models developed in this project was also further compared to a very well-established material model for soft tissues, which has been mostly used for cardiovascular tissues. In this comparison, strengths and computational weaknesses in all models were identified for modelling Achilles tendons. We concluded that the new developed model with transversely isotropic non-fibrillar matrix is the most suitable to use for modelling repairing tendons, as the fluid is the main component in the tissue and must be a key element during healing.

During the computational studies, we discovered that there is limited knowledge in how loading and the absence of it affects healthy Achilles tendons. Thus, in the next phase of the project experiments were conducted to investigate this further. The role of external loading was investigated in in vivo rat studies on both intact healthy tendons as well as tendons undergoing healing. The animal models can be simplified as following:
- Intact study: Healthy rats that can load one tendon normally and have a paralyzed calf-muscle that reduces loading. Tendons are harvested after 5 weeks.
- Healing study: The Achilles tendons of the right leg of the rats is transected during anesthesia. Half the animals have paralyzed calf-muscles to restrict loading and the other half can load the tendons normally. Tendons are harvested after 1, 2 and 4 weeks of healing respectively.
After harvest, all tendons were evaluated for their composition, structure and function. Fourier transform infrared spectroscopy was used to measure molecular composition of the tendons, where proteoglycan and collagen content were calculated. This was conducted at the Max IV laboratory in Lund, Sweden. To investigate tissue organization, Small Angle Xray Scattering, was used. Beamline time was granted at the Swiss Light Source at the Paul Scherrer Institut. Tendon viscoelastic function was studied with mechanical testing machine by performing hysteresis, creep and stress-relaxation tests.

The preliminary results show that the absence of mechanical loading changes the viscoelastic response of tendons, both in healthy and healing tendons. In healthy tendons, reduced loading signals a new mechanical environment and function of the tissue. This creates a response of increased collagen production and stiffer tendons. The new mechanical milieu changes also the energy-absorption capacity of the tendon, making it less efficient when not loaded.

In summary, computational models are great tools for investigating Achilles tendon biomechanics and mechanobiology. This project has developed a new material model that is highly suitable for modelling the biomechanical behavior of rat Achilles tendons during tension and additional experimental data on compression and shear would further improve the predictive capacity of the model. The experiments conducted discovered that Small Angle Xray Scattering is an excellent tool for investigating the mechanobiological effects on tendon organization, and that infrared spectroscopy is a good approach for studying tendon composition where small changes due to new environmental conditions might be difficult to capture with standard techniques. Additionally, mechanical loading was key for maintaining a normal viscoelastic response in intact healthy tendons. Loading also changed the viscoelastic behavior during healing. These findings suggest that the viscoelastic behavior of the tendon needs more research, as it could be a better way in the clinics to estimate tendon health and progression of healing.

Please follow the work progress on: http://bme.lth.se/research-pages/biomechanics/research/achilles-tendon-modelling/?no_cache=1

Contact

Hanna Isaksson, (Associate Professor)
Tel.: +4646 2224423
E-mail
Record Number: 196690 / Last updated on: 2017-04-05