Biomechanics and tissue engineering

Development of artificial scaffold for musculo-skeletal applications, especially in load-bearing situations, requires the consideration of biomechanical aspects for its integrity and its function. However, the biomechanical loading could also be used to favour tissue formation through mechano-transduction phenomena. Design of scaffold could take advantages of this intrinsic mechanical loading

Viscoelastic properties of soft tissues:application to knee ligaments and tendons

Ligaments play a central role in the stability of the knee. Due to the increase in sport activities of the young population, rupture of the anterior cruciate ligament (ACL) has become a frequent clinical problem. A surgical procedure replacing the deficient ligament is performed to restore the knee's initial stability. Although this surgical technique is widespread and well established, long term clinical results are inconsistent and the stability of the knee is not always restored, leading to premature arthrosis of the knee. This inconsistency of ACL replacement motivated the present study. "Optimal" ACL replacement only can be performed if the static and dynamic properties of the ligament are precisely known. In order to investigate these mechanical properties, an experimental set-up was developed to test human cruciate ligaments, as well as patellar tendon, which is commonly used for cruciate ligament replacement. Traction tests at different constant rates of elongation and stress relaxation tests were performed at controlled temperature (37°C) and humidity (100%). Results showed that cruciate ligaments and patellar tendons exhibit a non-linear elastic behavior in addition to a viscous behavior. The viscous behavior encompassed two phenomena: first a behavior where stress depended on strain rate (short term memory effects) and second a behavior where stress relaxed on a longer time scale (long term memory effects). In order to describe the different mechanical behaviors of the specimens in a general mechanical framework, a theoretical model was developed by simultaneously taking into account the non-linear elastic behavior, the short term memory effects and the long term memory effects. This proceeding satisfied the basic mechanical and thermodynamical requirements. The originality of the present model is based on the fact that the different mechanical behaviors are described in one framework allowing a compact description of the biomechanical properties of different soft tissues. The description of the short term memory effects is new in situations involving large deformations. The model is restricted by considering the specimens as isotropic, homogeneous and incompressible. The identification process of the different mechanical behaviors was facilitated with the proposed model. The non-linear elasticity was described with two parameters, the short term memory effects with one parameter and the long term memory effects with six parameters. No statistical differences were found between the parameters used for the anterior cruciate ligaments, the posterior cruciate ligaments and patellar tendons. The non-linear elastic behavior was implemented in a finite element code. The stress field in an ACL was calculated during a knee flexion and a tibial drawer test. The calculated stress field was inhomogeneous, with the highest stress in the anteriormedial part of the ACL. It was found that internal rotation of the knee generally increased the calculated stress in the ACL. These numerical results agree with in vitro studies given in the literature. The numerical results yielded a stress field in the ligament which was complementary to in vitro studies, where only the resultant ligament force can be measured. Several useful clinical conclusions can be drawn from the present biomechanical study. Diagnosis of an ACL rupture is generally performed by a contralateral comparison of antero-postero knee laxity (tibial drawer test) using a quasi-static load. However, diagnosis of an injured knee would be more accurate if the antero-postero load was dynamically applied to the knee: in this case, a knee with a rupture ACL would not show any effect, whereas a knee with an intact ACL would become stiffer with increasing the strain rate. In case of ACL replacement, the graft should be preconditioned in order to diminish the effects of stress relaxation. During the rehabilitation program after an ACL suture or replacement, flexion of the knee in an internal position should be omitted because internal rotation increases the stresses in the ligament

The influence of wear particles in the expression of osteoclastogenesis factors by osteoblasts

Orthopedic implant failures are often associated with peri-implant osteolysis. Particles generated from the wear process have been suspected to play an important role in this situation. Indeed, the peri-implant osteolysis could be due to the presence of particles stimulating the osteoclastogenesis process. We hypothesize then that the presence of a low particle concentration positively influences osteoblasts to produce osteoclastogenesis factors. If true, this hypothesis would then support the idea that the particles could be at the origin of the process leading to implant loosening. To check the validity of this hypothesis, we quantified in vitro the production of different genes involved in the osteoclastogenesis process using primary isolated human osteoblasts treated or not with particles. Results showed that low concentrations of particles might have a stimulating effect on osteoblasts to produce osteoclastogenesis factors as demonstrated by the increase of RANKL and CSF-1 gene expression in the particle group

Surgical preparation of bone-scaffold interface is critical for bone regeneration inside tissue engineering scaffold

The goal of this study was to investigate if the preparation of implantation site has an impact on bone formation inside tissue engineering scaffolds. For this purpose, two different drilling techniques were used to create a hole in distal femurs of rats before the insertion of a bone scaffold: a manually driven wood drill bit and an electrically driven metal drill bit. The size and the position of the hole were identical for the two cases. The bone volume, bone mineral density, and callus formation were assessed non-invasively using micro-CT tomography at several time points after implantation. The formation of bone and soft tissue inside scaffold were evaluated by histology. The bone structure around the holes made by the two techniques was compared ex vivo. The long-term study of bone formation showed that when a wood drill bit was used, the bone formation is accelerated by three weeks compared to when a metal drill bit was used. The ex vivo studies suggest that this result is due to the drilling methods differentially affecting the structure of the bone surrounding the generated defects

On the independence of time and strain effects in the stress relaxation of ligaments and tendons

The hypothesis of variables separation, namely the time and the strain separation in the relaxation function, is widely used in soft tissue biomechanics. Although this hypothesis is central to several biomechanical models, only few experimental works have tried to verify it. From these studies, contradictory results have been found. Moreover, it has recently been noted that no such experimental verification has been performed for ligament tissues. In this paper, an experimental method is developed to test the hypothesis of variables separation. This method is then used with human cruciate ligaments and patellar tendons. It is shown that the use of the variables separation hypothesis is justified at least for strain values lower than 16% for anterior cruciate ligament, lower than 12% for posterior cruciate ligament and lower than 6% for patellar tendon. The method presented in this paper could be used to verify the validity of variables separation for other tissues

Strategies for improving the repair of focal cartilage defects

Articular cartilage, together with skin, was predicted to be one of the first tissues to be successfully engineered. However cartilage repair remains nowadays still elusive, as we are still not able to overcome the hurdles of creating biomaterials corresponding to the native properties of the tissue, and which operate in joints environment that is not favorable for regeneration. In this review, we give an overview of the outcome of current cartilage treatment techniques. Furthermore we present current research strategies for improving cartilage tissue engineering

Can the increase of bone mineral density following bisphosphonates treatments be explained by biomechanical considerations?

OBJECTIVE: We hypothesized that bone mineral density increase following bisphosphonates treatments may be explained by the influence of the drug on the mechanical bone remodeling parameters. BACKGROUND: Patients treated with bisphosphonates continuously increase their bone mineral density. This increase is explained in the first 12-18 months following the treatment by the filling of the transient remodeling deficit. Recently, results of a clinical study of alendronate treatment over 7 years still show a continuous increase of bone mineral density. These results raised several questions regarding our understanding of bisphosphonates mode of action. METHODS: Bone remodeling is influenced by different factors including mechanical forces. In the present study, we propose then to consider the effect of bisphosphonates also under biomechanical considerations. RESULTS: Identification of the model with the clinical data showed that daily treatment of 10 and 20 mg alendronate decreased the bone turnover rate by 2% and 11%, respectively, in comparison with the 5 mg alendronate treatment. Moreover, the alendronate treatments decreases the resorption threshold stimulus by 19% (25%, 28%) for the 5 mg (10 and 20 mg, respectively) compared to placebo. CONCLUSIONS: The increase of bone mineral density following bisphosphonates treatment may then be explained by biomechanical considerations. Based on this description, bisphosphonates treatment may indeed change the susceptibility of bone to its biomechanical environment decreasing the mechanical threshold where bone should undergo resorption