Rachid Rahouadj

Low‐level laser therapy in collagenase‐induced Achilles tendinitis in rats: Analyses of biochemical and biomechanical aspects

NSAIDs are widely prescribed and used over the years to treat tendon injuries despite its well‐known long‐term side effects. In the last years several animal and human trials have shown that low‐level laser therapy (LLLT) presents modulatory effects on inflammatory markers, however the mechanisms involved are not fully understood. The aim of this study was to evaluate the short‐term effects of LLLT or sodium diclofenac treatments on biochemical markers and biomechanical properties of inflamed Achilles tendons. Wistar rats Achilles tendons (n = 6/group) were injected with saline (control) or collagenase at peritendinous area of Achilles tendons. After 1 h animals were treated with two different doses of LLLT (810 nm, 1 and 3 J) at the sites of the injections, or with intramuscular sodium diclofenac. Regarding biochemical analyses, LLLT significantly decreased (p < 0.05) COX‐2, TNF‐α, MMP‐3, MMP‐9, and MMP‐13 gene expression, as well as prostaglandin E2 (PGE2) production when compared to collagenase group. Interestingly, diclofenac treatment only decreased PGE2 levels. Biomechanical properties were preserved in the laser‐treated groups when compared to collagenase and diclofenac groups. We conclude that LLLT was able to reduce tendon inflammation and to preserve tendon resistance and elasticity.

A multilayer braided scaffold for Anterior Cruciate Ligament : mechanical modeling at the fiber scale

An adapted scaffold for Anterior Cruciate Ligament (ACL) tissue engineering must match biological, morphological and biomechanical requirements. Computer-aided tissue engineering consists of finding the most appropriate scaffold regarding a specific application by using numerical tools. In the present study, the biomechanical behavior of a new multilayer braided scaffold adapted to computer-aided tissue engineering is computed by using a dedicated Finite Element (FE) code. Among different copoly(lactic acid-co-(ε-caprolactone)) (PLCL) fibers tested in the present study, PLCL fibers with a lactic acid/ε-caprolactone ratio of 85/15 were selected as a constitutive material for the scaffold considering its strength and deformability. The mechanical behavior of these fibers was utilized as material input in a Finite Element (FE) code which considers contact/friction interactions between fibers within a large deformation framework. An initial geometry issued from the braiding process was then computed and was found to be representative of the actual scaffold geometry. Comparisons between simulated tensile tests and experimental data show that the method enables to predict the tensile response of the multilayer braided scaffold as a function of different process parameters. As a result, the present approach constitutes a valuable tool in order to determine the configuration which best fits the biomechanical requirements needed to restore the knee function during the rehabilitation period. The developed approach also allows the mechanical stimuli due to external loading to be quantified, and will be used to perform further mechanobiological analyses of the scaffold under dynamic culture.

A Poly(lactic-co-glycolic acid) Knitted Scaffold for Tendon Tissue Engineering: An In Vitro and In Vivo Study

We have designed a composite scaffold for potential use in tendon or ligament tissue engineering. The composite scaffold was made of a cellularized alginate gel that encapsulated a knitted structure. Our hypothesis was that the alginate would act as a cell carrier and deliver cells to the injury site while the knitted structure would provide mechanical strength to the composite construct. The mechanical behaviour and the degradation profile of the poly(lactic-co-glycolic acid) knitted scaffolds were evaluated. We found that our scaffolds had an elastic modulus of 750 MPa and that they lost their physical integrity within 7 weeks of in vitro incubation. Autologous rabbit mesenchymal stem cell seeded composite scaffolds were implanted in a 1-cm-long defect created in the rabbit tendon, and the biomechanical properties and the morphology of the regenerated tissues were evaluated after 13 weeks. The regenerated tendons presented higher normalized elastic modulus of (60%) when compared with naturally healed tendons (40%). The histological study showed a higher cell density and vascularization in the regenerated tendons.

Designing a three-dimensional alginate hydrogel by spraying method for cartilage tissue engineering

Cartilage tissue engineering strategies generally result in homogeneous tissue structures with little resemblance to native zonal organization of articular cartilage. The main objective of our work concerns the buildup of complex biomaterials aimed at reconstructing biological tissue with three dimensional cells construction for mimicking cartilage architecture. In this first step, our strategy is based on structure formation by simple and progressive spraying of mixed alginate and chondrocytes at different pressures. We report the first demonstration of spraying effect on chondrocytes inside an alginate hydrogel at short (i) and long terms (ii) and the mechanical behavior of a sprayed hydrogel by biomechanical tests (plane strain compression tests). Our results indicate clearly that during the first days of culture the cells were influenced by the construction method (spraying or molding, control method) with low viability and higher production levels of nitrite. From day 7, the cell behaviors become similar for both methods. Indeed after 28 days of culture, type II collagen was observed, showing the cartilage gene expression, then a similar behavior for all methods. Finally, we conclude that the mechanical performances of sprayed hydrogels was enhanced compared to the controls. We report here, for the first time, that it is possible to spray mixed alginate and chondrocytes with little damage for cells. Therefore, the sprayed hydrogel keeps not only the mechanical properties needed for cells, but also maintains the chondrocyte phenotype to induce cartilage.

Biomechanical and biochemical protective effect of low-level laser therapy for Achilles tendinitis.

For three decades, low level laser therapy (LLLT) has been used for treatment of tendinitis as well as other musculoskeletal diseases. Nevertheless, the biological mechanisms involved remain not completely understood. In this work, the effects of LLLT and of the widely used nonsteroidal anti-inflammatory drug, diclofenac, have been compared in the case of collagenase-induced Achilles tendinitis. Wistar rats were treated with diclofenac or laser therapy. The tensile behavior of tendons was characterized through successive loading-unloading sequences. The method considered 11 characteristic parameters to describe the mechanical behavior. It was shown that during the acute inflammatory process of the tendon, the mechanical properties were significantly correlated to the high levels of MMP-3, MMP-9 and MMP-13 expression presented in a previous paper (Marcos, R.L., et al., 2012). The treatment by non-steroidal anti-inflammatory drugs such as diclofenac sodium produces a low protective effect and can affect the short-term biochemical and biomechanical properties. On the contrary, it is shown that LLLT exhibits the best results in terms of MMPs reduction and mechanical properties recovery. Thus, LLLT looks to be a promising and consistent treatment for tendinopathies.

A thermodynamic approach with internal variables using Lagrange formalism. Part I: General framework

Abstract We present some reflections on the application of the Lagrangian formalism for continuous media locally uniform subjected to internal irreversible evolutions. The Lagrangian density, defined as the time derivative of a non-equilibrium thermodynamic potential, [Thermodynamics of Relaxation Processes using Internal variables within a Lagrange-formalism. P. Germain’s Anniversary Volume 2000. Contiuum Thermomechanics: the Art and Science of Modeling Matter’s Behaviour, 2000], contains all the symmetry properties of the system. The generalised Lagrange co-ordinates correspond to the state and internal variables of the time derivative of the generalised Gibbs potential. The latter being used within the framework of the De Donder’s method, must also account for the memory effect of the physical medium. This first part is devoted to the thermodynamic framework called the distribution of non-linear relaxations approach (DNLR) developed by C. Cunat on the basis of the generalised Gibbs’ relation.

Mechanical behaviour of a fibrous scaffold for ligament tissue engineering: Finite elements analysis vs. X-ray tomography imaging

The use of biodegradable scaffolds seeded with cells in order to regenerate functional tissue-engineered substitutes offers interesting alternative to common medical approaches for ligament repair. Particularly, finite element (FE) method enables the ability to predict and optimise both the macroscopic behaviour of these scaffolds and the local mechanic signals that control the cell activity. In this study, we investigate the ability of a dedicated FE code to predict the geometrical evolution of a new braided and biodegradable polymer scaffold for ligament tissue engineering by comparing scaffold geometries issued from FE simulations and from X-ray tomographic imaging during a tensile test. Moreover, we compare two types of FE simulations the initial geometries of which are issued either from X-ray imaging or from a computed idealised configuration. We report that the dedicated FE simulations from an idealised reference configuration can be reasonably used in the future to predict the global and local mechanical behaviour of the braided scaffold. A valuable and original dialog between the fields of experimental and numerical characterisation of such fibrous media is thus achieved. In the future, this approach should enable to improve accurate characterisation of local and global behaviour of tissue-engineering scaffolds.

A thermodynamic approach with internal variables using Lagrange formalism. Part II. Continuous symmetries in the case of the time–temperature equivalence

Abstract In the first part of this contribution, the Lie-symmetries of the principle of least action associated to the constitutive equations of the DNLR formalism of relaxation have been presented. We examine in this second part the continuous symmetries corresponding to the simple case of stress relaxation under isothermal conditions. The well-known principle of time/temperature equivalence is discussed in terms of variational symmetry for the Jacobi’s action functional, and connected to the Onsager’s relation near the thermodynamic equilibrium.

Computer-Aided Tissue Engineering: Application to the Case of Anterior Cruciate Ligament Repair

Tissue engineering has the potential to overcome the limitations associated with current reconstructions strategies of the Anterior Cruciate Ligament (ACL). However, the design of a scaffold satisfying the key requirements associated with ACL tissue engineering is a challenging task. In order to avoid a costly trial-and-error approach, computer-based methods have been widely used in the case of various applications such as bone or cartilage. These methods can help to define the best scaffold and culture conditions for a given list of criteria, and may also enable to predict the ultimate evolution of the scaffold and to better understand some mechanobiological principles. Some of these methods are reviewed in the current chapter, and are applied for the first time in the case of ACL tissue engineering. The morphological and mechanical properties of a new scaffold based on copoly(lactic acid-co-(\(\upvarepsilon \)-caprolactone)) (PLCL) fibers arranged into a multilayer braided structure will be assessed using dedicated numerical tools. Preliminary biological assessments are also presented, and some conclusions concerning the suitability of the scaffold and the interest of CATE in this case will be drawn.

Mechanical and Biological characterization of A Porous Poly‐L‐Lactic Acid‐Co‐ϵ‐Caprolactone scaffold for Tissue Engineering

This article presents a method for making highly porous biodegradable scaffold that may ultimately be used for tissue engineering. Poly(L‐lactic‐co‐ϵ‐caprolactone) acid (70∶30) (PLCL) scaffold was produced using the solvent casting/leaching out method, which entails dissolving the polymer and adding a porogen that is then leached out by immersing the scaffold in distillated water. Tensile tests were performed for three types of scaffolds, namely pre‐wetted, dried, and UV‐irradiated scaffolds and their mechanical properties were measured. The pre‐wetted PLCL scaffold possessed a modulus of elasticity 0.92±0.09 MPa, a tensile strength of 0.12±0.03 MPa and an ultimate strain of 23±5.3%. No significant differences in the modulus elasticity, tensile strength, nor ultimate strain were found between the pre‐wetted, dried, and UV irradiated scaffolds. The PLCL scaffold was seeded by human fibroblasts in order to evaluate its biocompatibility by Alamar blue® assays. After 10 days of culture, the scaffolds showed good biocompatibility and allowed cell proliferation. However, the fibroblasts stayed essentially at the surface. This study shows the possibility to use the PLCL scaffold in dynamic mechanical conditions for tissue engineering