Laboratory of Biomechanical Orthopedics 2009 Activity Report by vzk39560


									 Laboratory of Biomechanical Orthopedics

Inter-Institutional Center of Translational Biomechanics


               2009 Activity Report
Laboratory of Biomechanical Orthopedics
Following the very productive year 2008 in publication, 2009 was another
outstanding year. With 11 articles published in the major journals of biomechanics
and orthopedic research, and with many presentations by the LBO members in
international meetings, a clear visibility of the performed studies is achieved.
In parallel, the LBO has succeeded in obtaining important financial supports from
different sources, in particular from the Swiss National Science Foundation with 5
projects being actually granted through this competitive organization.
The projects developed at the LBO are at different levels from basic to applied
researches with anyway an overall strategy to bring the developed research to clinical
application, the so-called translational research. The core aspect is to use and develop
biomechanical descriptions to understand or develop new strategies in the field of
musculo-skeletal system. In particular, our projects are organized in four categories:
mechano-transduction, tissue engineering, biomechanics of joints and implants, and
drug delivery system.
A particularity of the LBO is to involve surgeons in most of the developed projects,
allowing us to obtain a more effective way for the translational aspect of our research.
Translation also means valorization, so we still continued our long lasting
collaborations with several industries such Tornier, Stryker or Symbios. In particular,
we also obtained financial support from the KTI to develop new solutions in
orthopedic implant with some of these companies.
Through the research strategy followed since several years, the LBO has developed
valuable knowledge in biomechanics and orthopedic research, which has found
already several applications in clinics. The development of projects at different levels
- from basic to applied research- also allowed us to define a fruitful collaboration with
the surgeons working at the CHUV.

Laboratory of Biomechanical Orthopedics      2                         
Table of contents
Staff                                                                                4

Collaborations                                                                       5

Projects report                                                                      6
            •   Biomechanical stimulus as osteogenic factor in scaffold              6
            •   Micro-fluidic chamber to quantify morphogen phenomena                7
    Biomechanics of joints and implants
            •   Neuro-musculoskeletal model of the shoulder                          8
            •   Effect of scapular tilting after total shoulder arthroplasty         9
            •   Mobility with reversed shoulder prostheses                           10
            •   Measurement of screw force in reversed shoulder prostheses           11
            •   Musculoskeletal model of the knee                                    12
            •   Effect of patient weight on polyethylene wear in a knee prosthesis   13
            •   Biomechanical considerations in revision knee arthroplasty           14
            •   Micromotion measurement around hip prostheses                        15
    Tissue engineering
            •   Characterization of human bone fetal cell                            16
            •   In vivo bone formation with fetal cells in sheep                     17
            •   cGMP parental cell banking of fetal articular cartilage              18
        Intervertebral disc
            •   Viscoelasticity of hydrogel: application to tissue engineering       19
            •   Hydrogel development for nucleus pulposus replacement                20
            •   Pilot study for the skin in GMP processing and recovery studies      21
    Drug delivery system
            •   Development of a deformation microcalorimeter                        22
            •   Bone remodeling model around a drug delivery system                  23

Publications                                                                         24

Funding                                                                              27

Contact                                                                              28

Laboratory of Biomechanical Orthopedics      3                          
During the year 2009, the following people were directly involved at the “LBO”:
Lab director
    •   Prof. Dominique P. Pioletti
Group leaders
    •   Prof. Lee Laurent-Applegate (OCUT/UNIL)
    •   Dr. Alexandre Terrier
    •   Virginie Kokocinski
Medical advisors
    •   Prof. Alain Farron (DAL/Orthopedics)
    •   Prof. Bertrand Jaques (Maxillo-facial Surgery)
    •   Prof. Brigitte Jolles-Haeberli (DAL/Orthopedics)
    •   Dr. Wassim Raffoul (DAL/Reconstructive Surgery)
    •   Dr. Constantin Schizas (DAL/Orthopedics)
    •   Dr. Michael Wettstein (DAL/Orthopedics)
    •   Dr. Pierre-Yves Zambelli (DAL/Pediatrics)
Post-doctoral fellows
    •   Dr. Nathalie Krattinger
Lab assistants
    •   Sandra Jaccoud
    •   Corinne Scaletta (OCUT/UNIL)
    •   Vittoria Brighenti
    •   Martin Aeberhard
    •   Francesco Merlini
    •   Silvio Ramondetti
PhD students
    •   Philippe Abdel-Sayed
    •   Ana Borges (LTC)
    •   Salim Darwich
    •   Michael Gortchacow
    •   Jérôme Hollenstein (UCSD)
    •   Aurélie Quintin
    •   Alireza Roshan Ghias
    •   Marion Röthlisberger
    •   Arne Vogel
MS students
    •   Philippe Abdel-Sayed
    •   Line Aschwanden
    •   Florian Herzog

Laboratory of Biomechanical Orthopedics      4                     
    •   Laboratory of Comp. Polymer Tech. (Dr. P.E. Bourban, Prof, J.A. Manson)
    •   Laboratory of Movement Analysis and Measurements (Prof. K. Aminian)
    •   Laboratory of Automatic Control (Dr. P. Muellhaupt)
    •   Laboratory of Polymer (Prof. H.A. Klok)
    •   Dept. of Bone Diseases, HUG, Genève (Prof. S. Ferrari, Prof. J. Caverzasio)
    •   Neurosurgery, CHUV (Dr. E. Pralong)
    •   Tissue Engineering Laboratory, University Hospital, Basel (Prof. I. Martin)
    •   Musculoskeletal Research Unit, University of Zurich (Prof. B. von
    •   IRMAR, University of Rennes 1, France (Prof. L. Rakotomanana)
    •   INSERM, University of Nantes, France (Prof. J.M. Bouler)
    •   Department of Biotechnology, IIT Madras, India (Prof. A. Jayakrishnan)
    •   Department of Mechanical Eng., Colombia University, USA (Prof. C. Jacobs)
    •   Department of Bioengineering, UCSD, USA (Prof. B. Sah)

    •   Osteosynthesis Division, Stryker
    •   Symbios Orthopédie
    •   Tornier Implants Chirurgicaux
    •   Degradable Solutions

Laboratory of Biomechanical Orthopedics    5                      
      Biomechanical stimulus as osteogenic factor in
Collaborator: A. Roshan-Ghias
Supervisor: D.P. Pioletti

In clinical situations, bone defects are often located at load bearing sites. Tissue
engineering scaffolds are future bone substitutes and hence they will be subjected to
mechanical stimulation. The goal of this study was to test if cyclic loading can be
used as stimulatory signal for bone formation in a bone scaffold. PLA/ 5% β -TCP
scaffolds were implanted in both femoral condyles of eight rats.

Results obtained in 2009
Both femoral condyles of 8 female Wistar rats were drilled and PLA scaffolds were
implanted inside. No cells or growth factors were added in the scaffolds. Three days
after surgery, the right knees were loaded and the left knees were kept as control. A
compressive load of 10 N at 4 Hz for 5 minutes was applied by a compression
machine 5 times every other day. Both knees were scanned in vivo using micro-CT at
2, 4, 6, 9 and 13 weeks after surgery (Figure 1 left). Accordingly, bone volume (BV)
inside scaffolds was measured. A linear mixed-effect model was used to analyze BV
as a function of time and loading. It was found that loading has enhanced the rate of
bone formation by 28% (p-value = 0.0001) and the loaded group had higher amount
of bone formation at 13 weeks compared to control group (Figure 1 right).

Figure 1: Left: bone formation inside scaffold at 13 weeks. Right: bone volume for control and loaded
        groups over time. Note that both the intercept and the slope are significantly different

Perspective for 2010
In vivo study will be continued by studying the role of architecture of scaffold on the
effect of mechanical stimulation on bone formation inside scaffold.

Laboratory of Biomechanical Orthopedics            6                              
        Micro-fluidic chamber to quantify morphogen
Collaborator: M. Gortchacow
Supervisors: A. Terrier, D.P. Pioletti

For cementless implants, the initial bone healing phase is crucial for the implant's
survival. The complex biological processes occurring during this healing phase are
related to mechanical phenomenon. To address the mechanical effect on the
cementless peri-implant healing process, we propose two hypothesis. First, load on
the peri-implant affects the healing tissue fate mainly due to its influence on the
differentiation-migratory stage of bone regeneration, which concerns the human
mesenchymal stromal cells (hMSCs). Secondly, this loading dependency can be
explained by morphogen advective flow induced by strains within the healing tissue.

Results obtained in 2009
To study the effect of flow and colony size on hMSCs differentiation towards
osteoblasts, three main subjects were tackled: the flow chamber device; micro contact
printing for the colony size regulation; and differentiation quantification of hMSCs. a
A peristaltic pump in a closed circuit was used to induce fluid flow in the previously
designed PDMS flow chamber (Figure 2).

Figure 2. Left: two flow chamber devices with hMSCs under flow. Right: cells cultured for 5 days after µContact
                            printing, original printed patters is indicated in yellow.

Diverse methods and stages of the printing were tested, involving: PDMS coating;
covalently linking fibronectin to the seeding surface; immunofluorescence. Replacing
the glass cover slips by polystyrene ones resulted the best method, allowing cells to
maintain the desired pattern for at least one week (Figure 2).

Perspective for 2010
We will continue the experiments with fluid flow and verify immunofluorescence
procedure to test the above-mentioned hypothesis.

Laboratory of Biomechanical Orthopedics                 7                                   
       Neuro-musculoskeletal model of the shoulder
Collaborator: M. Röthlisberger
Supervisors: A. Terrier, A. Farron, D.P. Pioletti

Neuromuscular diseases alter the usage of the shoulder joint, which might lead to
osteoarthritis. However, the link between neuromuscular diseases and osteoarthritis is
not yet clear. To investigate the differences (e.g. with respect to the glenohumeral
contact force or contact pattern) between a healthy subject and a subject with
neuromuscular diseases, a neuromusculoskeletal model of the shoulder joint will be
developed and certain diseases will be simulated. Therefore, a neuromusculoskeletal
model of a healthy subject has to be created in a first step, thereafter the disease can
be implemented into the healthy (and validated) model and the question with respect
to the above mentioned link can hopefully be answered. In summary, the final goal of
this project is to have a closed loop neuromusculoskeletal model, which allows one to
model different neuromuscular diseases.
This interdisciplinary project is done in a strong collaboration with the Laboratoire
d’automatique (EPFL-LA) and the CHUV (A. Farron and E. Pralong). The EPFL-LA
develops the control algorithm needed for getting a closed loop model and the two
MD from the CHUV are the contact persons for medical questions.

Results obtained in 2009
Two models exist already: a FE model (in Abaqus; developed by Terrier et al., 2007)
for humeral abduction, and a simple control model (in Matlab; developed by
Aeberhard et al., 2009) which can perform different movement. Both models are still
open loop. The FE model was improved by implementing a natural motion of the
scapula during abduction (in vivo data from Borstad and Ludewig, 2002). By then the
scapular motion was assumed to have just a motion component in one direction and
followed a constant scapulohumeral rhythm.

Perspective for 2010
A neuromusculoskeletal model of a healthy subject will be developed. In a first step,
muscles will be added to the already existing FE model and activities of daily living
(ADL) will be simulated. This first step will allow us to obtain the moment arms
during the ADL. Optimization criteria have to be defined for getting the
corresponding muscular forces.
For getting a closed loop model, different elements of the sensorimotor system have
to be implemented in the model (e.g. muscle spindles).

Laboratory of Biomechanical Orthopedics      8                        
          Effect of scapular tilting after total shoulder
Collaborator: M. Röthlisberger
Supervisor: A. Terrier, A. Farron

The kinematics of the scapula might be altered due to neuromuscular diseases or age.
In older patients, one can often see an increased thoracic kyphosis, which leads to an
increase of the anterior tilt of the scapula. It is not yet known which consequences an
altered scapular orientation has on the glenohumeral contact force, contact pressure
and contact pattern of an anatomical total shoulder arthroplasty. The numerical
musculoskeletal model developed by Terrier et al. (2007) was used to simulate an
abduction of the humerus in the scapular plane. The motion of the scapula was
implemented using in vivo measurements from Borstad and Ludewig (2002). For the
pathological scapular position an initial offset of 10° anterior tilt was simulated.

Results obtained in 2009
The anterior tilt of the scapula increases the glenohumeral contact force and the
contact pressure during the entire simulated abduction motion. The increase was
largest at 30° of abduction and is getting smaller towards 120° of abduction. The
anterior tilt induces an eccentric contact pattern during the first 60° of humeral
abduction (Figure 3). It could be seen that an altered initial position of the scapula has
an influence on the investigated factors.

 Figure 3. Patterns of contact pressure for different abduction angles (grayscale corresponding to 5, 10, 15, and

Perspective for 2010
The consequences of the altered orientation of the scapula due to the thoracic
kyphosis are not yet known and should be further evaluated. Maybe the current
implant design should be adapted to the pathological scapular orientation in older

Laboratory of Biomechanical Orthopedics                   9                                    
         Mobility with reversed shoulder prostheses
Collaborator: S. Ramondeti
Supervisor: A. Terrier, A. Farron

Reverse shoulder prostheses balance the deficiency of the rotator cuff muscles, by
semi-constrained articular surfaces and a medial displacement of the rotation centre.
However, the rotation centre medialization induces mechanical impingements among
bones and implants. Several ideas have already been proposed to reduce the
impingements and improve the mobility of reverse prostheses: lateral or inferior
displacement of the rotation centre, or increase of the glenosphere size. The effects of
these design parameters have only been evaluated on the maximal range of abduction,
for simple movements. The aim of this study was to obtain the complete 3D
impingement map for different glenosphere positions and sizes and to relate this
mobility map to typical activities of daily living.

Results obtained in 2009
A geometric model of the scapula and humerus was built from CT data of a normal
cadaver shoulder. A CAD software was used to perform the bone resection and the
prosthesis implantation according to manufacturer’s recommendations (Figure 4). The
complete mobility map of different reversed designs was measured with the CAD
software and was then compared to kinematic measurements on healthy subjects, for
4 important daily living activities: hand to mouth, hand to contra lateral shoulder,
hand to back pocket, combing hair. Each movement was divided in three parts: the
first third of the movement, the middle and the last third. For each part of the
movement, the set of all allowed positions of the prostheses was compared to the
glenohumeral angles of the healthy shoulder. Finally, the percentage of the allowed
movement relative to the healthy shoulder motion was computed. In summary, we
mainly observed an improved mobility with inferior displacement of the rotation
centre and increased glenosphere size.

              Figure 4. Reverse shoulder prostheses of two different sizes in the CAD model.

Perspective for 2010
A clinical study on reverse implants will validate clinically these findings.

Laboratory of Biomechanical Orthopedics              10                              
         Measurement of the screw forces in reversed
                  shoulder prostheses
Collaborator: M. Gortchacow
Supervisors: A. Terrier, A. Farron

Reversed shoulder arthroplasty is an accepted treatment for glenohumeral arthritis
associated to rotator cuff deficiency. However, because of the small glenoid bone
volume available for the fixation of this semi-constrain prosthesis, the determination
of the optimal baseplate fixation is still an open question. Most designs use peripheral
screws to provide the baseplate primary stability, but the screw compressive force and
associated screwing torque are unknown. We developed an experimental setup to
measure the compressive force, screwing torque and screwing angle, for the anterior
and posterior non-locking screws of the Aequalis baseplate.

Results obtained in 2009
Measurements were performed on 6 human cadaveric scapulae, during the whole
screwing process up to bone failure. For each screw, we measured the surgical and
failure force and torque, and bone quality using μCT. Screw compressive force was
statistically correlated with bone quality.

 Figure 5. Typical measurements of F-Alpha (continuous) and M-Alpha (dotted) diagrams, showing the surgical
 stop angle αsurg, surgical compressive force Fsurg, maximal compressive force Fmax, surgical screwing torque Msurg
                       and maximal screwing torque Mmax of a nonlocking compression screw

Perspective for 2010
The results of this experimental study on cadaveric scapulae will be used with
numerical models to test different screw configurations for the improvement of the
fixation of the baseplate of reversed shoulder prostheses.

Laboratory of Biomechanical Orthopedics                   11                                    
                 Musculoskeletal model of the knee
Collaborator: S. Ramondetti
Supervisors: A. Terrier, B. Jolles, D.P. Pioletti

Various aspects of the knee prosthesis designs are still not completely understood, and
not fully optimized for the long-term success of total knee arthroplasty. The aim of
this study was to develop a musculoskeletal model of the knee for several loaded
activities of daily living, and to compare within the same model and in the same
conditions different prosthetic designs.

Results obtained in 2009
A musculoskeletal model of the knee was developed and a knee prosthesis was
inserted. The tibial, femoral and patellar components of a mobile ultra-congruent knee
prosthesis (FIRST, Symbios, Switzerland) were positioned according to manufacturer
recommendations. Kinematics measurements during squatting, walking, stairs
climbing and descending were performed in collaboration with the Laboratory of
Movement Analysis and Measure (EPFL-LMAM). Each loaded (bodyweight)
movement was simulated by controlling knee flexion through the quadriceps muscle.
Muscle activation pattern was estimated from EMG data and synchronized by a
feedback algorithm.

                     Figure 6. The musculoskeletal knee model during a gait cycle.

Perspective for 2010
The model will be used to compare various biomechanical aspects of 4 different knee
prosthesis designs.

Laboratory of Biomechanical Orthopedics             12                     
    Effect of patient weight on polyethylene wear in a
                      knee prosthesis
Collaborator: S. Ramondetti
Supervisor: A. Terrier, B. Jolles

The wear of the polyethylene component is a key factor in the long term success of
total knee arthroplasty. Although patient weight has been reported to be one of the
possible causes for excessive wear, clinical studies comparing obese and nonobese
patients are contradictory.   Therefore, the goal of this study was to evaluate the
effect of the patient weight on the volumetric wear rate of a mobile bearing ultra-
congruent knee prosthesis.

Results obtained in 2009
A numerical musculoskeletal model of the knee was used to predict the wear rate
caused by a loaded squat movement, which was actively controlled by the quadriceps
muscle. The linear wear was computed from the Archard’s law, with a pressure
dependent factor measured experimentally. Linear wear was then extended to
volumetric wear rate. Four values of patient bodyweight were tested: 60, 80, 100 and
120 kg. This numerical study provided data consistent with the results reported in
literature and predicted that polyethylene wear is not proportional to patient weight
(Figure 7), at least for this mobile ultra-congruent knee prosthesis. As a consequence,
the obtained data indicated that this type of knee prostheses could be used with
overweighed patients who would otherwise not be accepted for this surgery.

    Figure 7. Volumetric wear rate (mm3/million cycles) versus patient bodyweight, for 3 angles of flexion.

Perspectives for 2010
The wear algorithm will be used to predict the wear rate of different knee prostheses
and, besides squat, other movements will be analyzed. Additionally, we plan to
improve the current wear algorithm to change the shape of the articular surface, in
order to predict a long-term wear.

Laboratory of Biomechanical Orthopedics                 13                                   
       Biomechanical considerations in revision knee
Collaborator: A. Roshan-Ghias
Supervisors: A. Terrier, D.P. Pioletti

Following the failure of knee implant, another surgery is needed which is called
Revision Knee Arthroplasty (RKA). In this surgery, the damaged bone should be
removed and replaced by a bone substitute. In recent years, artificial bone scaffolds
have been proposed as a suitable bone substitute, and we have shown that mechanical
stimulus can enhance bone formation in a rat model. To investigate the biomechanical
aspect inside the scaffold used in RKA, we developed a realistic model of RKA.
Furthermore, we developed a micro-FE model of scaffold to investigate the
mechanical stimulus inside pores.

Results obtained in 2009
Tibia of a cadaver was CT scanned and reconstructed in Amira and prepared in
Geomagic for FE meshing. The geometry of the implant was obtained from the
manufacturer. The implant was virtually placed inside the tibia by a surgeon. The
meshing was done in ABAQUS. Gait induced loads were applied on the tibial
compartment of the implant. Linear material properties were assumed for all
materials. Finally, the model was solved and strain was estimated inside the scaffold.
In order to study the mechanical stimulus inside the scaffold, a micro-FE modeling
approach was chosen. The geometry of the scaffold was obtained by micro-CT
scanning and was converted to a voxel-based FE mesh using an in-house software.
The mesh was imported in ABAQUS for FE analysis. The mechanical properties of
the scaffold were obtained from back-calculation technique. The pores were assumed
to be filled with granulation tissue and the appropriate mechanical properties were
assigned to them. Octahedral shear strain was estimated inside the pores as the
biomechanical stimulus.

  Figure 8. Left: the RKA model. Scaffold is shown with an arrow. Right: Aapart of the scaffold modeled using
                                              micro-FE technique.

Perspective for 2010
The two models will be further merged together to estimate the mechanical stimulus
inside scaffold. The clinical aspects will be addressed and emphasized.

Laboratory of Biomechanical Orthopedics                 14                                  
   Micromotion measurement around hip prostheses
Collaborator: M. Gortchacow
Supervisors: A. Terrier, M. Wettstein, D.P. Pioletti

It has been established that primary stability of femoral stems is a determinant of the
clinical success of cementless total hip arthroplasty. Excessive interface micromotions
may lead to a peri-implant fibrous tissue formation resulting in aseptic loosening of
the implant. The effect of micromotion on the tissue outcome remains still unknown.
However, it is becoming increasingly clear that interstitial fluid flow is the primary
mechanism by which bone cells perceive changes in their mechanical environment.
Therefore, to estimate the interstitial peri-implant fluid flow, a detailed measurement
of simultaneously normal and tangential micromotion is required as well as a large
distribution of micromotion values along the peri-implant region, both of which have
not been achieved thus far. The objective of this study is to assess the feasibility of
micromotion measurement on human cadaveric femurs using spherical Tantalum
beads as markers and micro computed tomography (µCT).

Results obtained in 2009
Micromotion of a loaded stem was measured using Ta beads of 800µm in diameter.
This was performed for loads of up to 1200N (Figure 9), tracking the beads using a
µCT scanner. Error was estimated to +/- 20 µm. This work was presented in diverse
congresses including an oral presentation in the ISB.

                Figure 9. Micromotion of diverse Ta beads at different implant load values.

An improved method was also tested by adding inox beads of diameters of 200, 300
and 600µm to the Ta beads in order to obtain more measuring points, allowing also to
reduce costs considerably. Other scanning and reconstruction parameters were
modified too. A new code in Mathematica was developed to process the images and
measure the micromotion. Micromotion errors were computed for a non-loaded case
resulting in an experimental error of ~+/-15µm for the 600µm beads, the most
accurate of the three.

Perspective for 2010
Depending on availability of suitable human femurs, the perspectives are to perform a
micormotion comparative study between Standard and SPS hip Symbios stems.

Laboratory of Biomechanical Orthopedics               15                            
             Characterization of human bone fetal cell
Collaborator: N. Krattinger
Supervisors: L.A. Laurent-Applegate, J. Caverzasio, D.P. Pioletti

Considering the increasing clinical potential of fetal cells for tissue engineering,
human bone fetal cells (hFBC) have been characterized in vitro. We previously
described that these cells proliferate more rapidly than adult primary osteoblasts and
can produce a mineralized bone matrix when cultured in an osteogenic medium. To
date, little information is available concerning the behavior of fetal bone cells in
culture and of factors regulating their growth and differentiation. Since hFBC have
characteristics of progenitor cells, we compared their capacity to proliferate and
differentiate with those of human mesenchymal stem cells (hMSC) cultured in an
osteoinductor medium.

Results obtained in 2009
Evaluation of the proliferation rate demonstrated that hFBC proliferated more rapidly
in α-MEM medium. Gene expression analysis demonstrated higher mRNA levels of
runx2, alp and ocn in hFBC cultured in basal conditions. Similar mRNA levels were
observed in hMSC after induction of differentiation in osteogenic culture conditions
(Figure 10A). Expression of Sox-9, which is related to chondroblastic commitment,
was very low in hFBC as well as in hMSC, compared to expression levels observed in
fetal cartilage-derived cells (hFCC) (Figure 1B). In hFBC, BMP-2 associated with
osteoinductive factors induced increased proliferation rate, whereas this association
decreased differentiation potential. By an Alizarin Red assay, we showed that hFBC
deposited a higher quantity of calcified extracellular matrix than hMSC did, when
cells were cultured in osteogenic conditions (Figure 11). In conclusion, we reported
that human fetal bone cells have characteristics of osteoprogenitors and are more
advanced in their osteogenesis development compared with mesenchymal cells.

Figure 10. Quantitative validation of runx-2 (A) and sox-   Figure 11. In vitro mineralization. (A): Extracellular
9 (B) gene expression levels in response to osteogenic      matrix mineralization was induced on confluent
factors. hFBC and hMSC were maintained in αMEM              monolayers of hFBC and hMSC by addition of osteogenic
medium in presence of osteoinductive factors for 10 days.   factors (OM). Then they were fixed, and stained for ALP
Fetal cells isolated from mixed cartilage (hFCC), and       activity after 10 days of culture. Calcium deposition and
cultured in chondrogenic conditions for 10 days were        bone nodules formation were evaluated by Alizarin Red s
used as reference for sox-9 mRNA. MG-63 osteoblast-         (ARS) and von Kossa staining, respectively, four weeks
like cell line, maintained in αMEM base medium without      post-treatment. (B): The degree of in vitro calcium
any supplemented factors, served as a control source.       deposition was determined using Alizarin Red S (ARS)
mRNA quantification was shown as 2-ΔΔCT values.             quantification method.

Laboratory of Biomechanical Orthopedics                 16                                   
       In vivo bone formation with fetal cells in sheep
Collaborators: S. Jaccoud, C. Scaletta
Supervisors: L.A. Laurent-Applegate, B. von Rechenberg, D.P. Pioletti

A cell bank was established from a human 14 week male fetus femur (Organ donation
was obtained following Ethics Committee Protocol # 62/07: “Development de fetal
cell banks for tissue engineering”). From the master bank, a working bank has been
established and 80 frozen vials containing each 2.4x106 cells have been produced and
it has been verified that the mode of injection with a hyaluronic acid gel did not affect
the cell viability. To evaluate the potential of bone healing of human fetal cells, an in
vivo model in sheep was used. The in vivo model consists in drill holes of 8 mm
diameter and 13 mm depth created within the proximal and distal humerus and femur
of sheep. 10 sheep were used in this study having 8 drill holes per animal, which were
filled either with hyaluronic acid gel and cells, hyaluronic acid gel alone or left empty
as negative controls. The fetal cells were thawed only 30 minutes before being
injected and reconstituted in the hyaluronic acid gel, which were easily applicable and
polymerized after injection. The short time for reconstitution of cells and mixing them
with hyaluronic acid gel makes this end product very easy to use for the surgeon and
presents a decisive advantage for future clinical applications.

Results obtained in 2009
All injection sites healed well and no infections or irritations were visible, neither
clinically, nor at the time of macroscopic evaluation after sacrifice of the sheep at 2,
4, 8 and 12 week post-injection. Radiological results showed that drill holes injected
with cells appeared more radio dense compared to those filled only with hyaluronic
acid gel alone. Histological evaluation demonstrated that no immunological or
inflammatory reactions were induced by the injection of the human fetal cells
(xenotransplantation), which confirms previous results obtained in rat, mouse and
rabbit. A tendency was observed toward more bone formation when fetal cells were
injected, however no statistical significance was observed, probably due to the
important biological variation of the results.

                      8 sites

 Figure 12. Bone formation observed radiologically in drill holes treated with human bone fetal cells at 12 weeks
                                            compared to empties.

Perspective for 2010
These encouraging results for the in vivo model allowed us to test the injection of the
fetal cells delivered following frozen aliquot dosages and to verify that no
inflammation or immunological reactions were generated thus permitting to assess the
safety validation in a large animal model. Development of a cGMP Master Cell Bank
designated for clinical use can now be evaluated.

Laboratory of Biomechanical Orthopedics                  17                                   
  cGMP parental cell banking of fetal articular cartilage
Collaborators: S. Darwich, C. Scaletta, M.C. Osterheld
Supervisors: L.A. Laurent-Applegate, W. Raffoul, D.P. Pioletti,

A feasibility study for the isolation, expansion and development of a parental cell
bank from fetal cartilage was undertaken. In order to obtain consistent batches of fetal
cells for performing research as well as for clinical applications, reproducible and
traceable processes of cell banking has to be accomplished and documented. All
cGMP processing was done in a dedicated culture facility in the CHUV (BH 05-516).
Organ donation was obtained following Ethics Committee Protocol # 62/07:
“Development de fetal cell banks for tissue engineering”. Donor screening was
following the regulatory requirements of SwissMedic.

Results obtained in 2009
Tissue dissection (~2 mm2) by the fetal pathologist was successfully performed to
isolate articular cartilage located in the elbow joint. Tissue was micro-dissected and
dispersed into three 10 cm tissue culture plates by mechanical attachment to scalpel-
scored surfaces. Cell outgrowth was seen following one week and at two weeks,
expansion of fetal articular cartilage was accomplished. The parental cell bank was
established with 100 vials of cells with 5-10 x106 cells and stored in vapor-phase of
liquid nitrogen following cGMP stocking conditions as required by regulatory affairs
for therapeutic products.

 Figure 13. Processing of fetal articular cartilage tissue to produce consistent cell banks for research and clinical
 use. 100 vials of parental articular cartilage were produced which would allow for multiple research projects and
importantly, sufficient vials to be submitted to cGMP manufacturing to produce cells for therapeutic applications.

Perspective for 2010
These encouraging results allow us to have a cGLP clinical fetal cell cartilage bank
prepared for complete characterization including a validation study in vivo for cell
therapy of cartilage.

Laboratory of Biomechanical Orthopedics                    18                                     
     Viscoelasticity of hydrogel: application to tissue
Collaborators: A. Vogel, L. Aschwanden
Supervisor: D.P. Pioletti

In the field of biomechanics, we are interested in finding a quantitative variable to
describe mechanotransduction and convection. Viscoelasticity seems to be a good
candidate. Indeed, viscoelasticity may arise from both internal mass transport (fluid
flow) and from microstructural interactions, resulting into a time dependent and
macroscopically observable behavior. Therefore, it seems worthwhile to investigate
any correlations between viscoelastic properties of biological tissues and ECM
production. In the context of intervertebral disc degeneration, in which aggrecan
production and viscoelastic properties of the nucleus pulposus both decrease with age,
we have mechanically stimulated an alginate fetal cell construct at different
(mechanical) hysteresis levels and assessed aggrecan production level by

Results obtained in 2009
It was observed that aggrecan production is not affected by the loading condition, but
rather by the location of the cells in the alginate construct. Indeed, in the superficial
region where deformations are small compared to the central region, positive
aggrecan production was observed. This could be explained as the cells located at the
superficial region are more exposed to nutriments than those located in the central

Figure 14. Difference of hysteresis level in respect of    Figure 15. Aggrecan production after 4 weeks in all
loading frequency.                                         groups at superficial region of the gel.

Perspective for 2010
The experimental method will be ameliorated in consideration of the outcomes of this
study. In particular, we will apply dynamic loading on a hydrogel scaffold with more
pronounced viscoelastic properties than alginate and will optimize the nutriment
distribution throughout the gel.

Laboratory of Biomechanical Orthopedics                   19                                
         Hydrogel development for nucleus pulposus
Collaborator: A. Borges
Supervisors: P.E. Bourban, D.P. Pioletti, C. Schizas, J.A. Manson

The mechanism of load bearing of the nucleus pulposus (NP) is defined by its ability
to swell and to support the intra-discal pressure. Once degenerated, the NP loses its
faculty of load bearing. Up to now, the solution to degeneration is vertebral fusion or
total disc replacement. Surgical techniques are however shifting towards preservation
techniques and NP replacement encounters a very large interest. Several synthetic
NPs are therefore investigated in order to restore IVD functions. This study is focused
on injectable, UV curing composite hydrogels for the NP replacement.

Results obtained in 2009
The synthesis of new methacrylated monomers based on a surfactant, Tween 20,
yielded in reproducible and relatively high conversion gel. Tween 20 trimethacrylate
(T3), a branched molecule, was then used as a cross-linker in two hydrogel systems
made of T3 and N-vinyl-2-pyrrolidone (NVP) and T3 and 2-hydroxyethyl methacry-
late (HEMA). The study of the curing kinetics by photorheology and photo
differential scanning calorimetry of both systems showed that the concentration of T3
influenced the final cross-linking density (Figure 16) whereas the amount of initiator
and of UV intensity influenced the time of curing. The mechanical behavior of
T3/NVP hydrogels was strongly dependent on the concentration of T3 and on the
water content of the network. It was also proven that the swelling behavior was
dependent on the crosslinker concentration. The mechanical behavior of hydrogels
was investigated at different conditions (dried, after polymerization and after

 Figure 16. Storage modulus (a) and viscosity (b) of a T3/NVP gel measured as a function of irradiation time for
    different T3 concentrations at RT and at 15 mW/cm2 and with 10%vol of initiator (15% of strain, 10 Hz).

Perspectives for 2009
In order to prove the feasibility of using the produced hydrogels as NP implants,
cadaveric studies should be conducted. This would allow the investigation of suitable
injection methods and the behavior of hydrogels in their future biological
environment. Animal studies, using rabbits as model, should also be performed.

Laboratory of Biomechanical Orthopedics                  20                                   
       Pilot study for the skin in GMP processing and
                       recovery studies
Collaborator: C. Scaletta
Supervisor: L.A. Laurent-Applegate

The purpose of this report is to accurately describe the materials and methods that
were used during a pilot study under cGLP conditions that was conducted in order to
determine an optimal growth strategy for the production of a FE002-SK Master Cell
Bank derived from fetal skin parental cell banks. Parameters that were investigated
included cell seeding density at point of initiation and culture incubation time prior to
harvest. Relative cell counts were performed at 3 different time points in order to
ascertain the optimum conditions in order to maximize the cell yield during the GMP
Master Cell Bank production for fetal skin cells to be characterized and validated for
clinical use. This is one of the major milestones for developing a therapeutic agent.

Results obtained in 2009
After the FE002-SK fetal skin cells had been cultured and consequently harvested at
each of the designated time points post-initiation, it was possible to determine the
optimum strategy to maximize the growth potential of the cells. The cell count data
obtained from the cultures that were generated during the pilot study are shown in the
Table below and it can be seen that the process was most productive when cells were
initiated with a relative seeding density of 2.625 x 105 viable cells/flask and cultured
for a period of 12 days when compared with the relative data sets that were displayed
by cultures that were grown under the different conditions. Remarkably, viability
studies and recovery studies are at an optimum with 98-99% recovery shown (young
and adult human cells are generally around 50-60%).

                                     Table 1: Harvest Point [12 days]
Initiation Seeding    Viable         Total Viable                                                  No. of
                                                      Total Cells/mL Total Cells     % Viability
      Density        Cells/mL           Cells                                                      Vials

                                                                        4.07 x 107
  Low [2.625 x                   5                7                 5
                     8.22 x 10        4.03 x 10         8.30 x 10        (~8.14 x       99%          4

                                                                        7.01 x 107
  High [5.25 x                   6                7                 6
                     1.42 x 10        6.96 x 10         1.43 x 10        (~1.40 x       99%          7

Perspective for 2010
These encouraging results for successful transfer of technology allow us to define
specific conditions for cGMP manufacturing which will be programmed now in the
first trimester of this year. Following the full development of the Master Cell Bank,
the Working Cell Bank will then be manufactured and full screening and testing will
be done. Final validation should be accomplished before the end of the year.

Laboratory of Biomechanical Orthopedics                 21                               
     Development of a deformation microcalorimeter
Collaborator: A. Vogel
Supervisors: D.P. Pioletti

In the context of material science, calorimetry has proven to be a valuable tool in
studying various reversible and irreversible internal processes of polymers. In
parallel, hydrogels have shown to be promising in tissue engineering as they provide
a 3D and more physiological environment than classic culture techniques.
Furthermore, hydrogels may be mechanically loaded to provide appropriate
mechanical stimuli to the scaffold, a non-negligible factor to drive matrix deposition.
According to this knowledge, we are developing a deformation calorimeter capable in
applying mechanical loads to a hydrogel construct and capture heat exchanges with
the environment. This method may give us invaluable insights on the microstructural
interactions under loading conditions, and maybe allow us to develop a framework to
optimize tissue engineered scaffolds.

Results obtained in 2009
The calorimetric sensors have been built and are sensible up to 0.1 [mW]. The
mechanical dissipation of the silicone encapsulation device that holds the hydrogel
specimen is about an order magnitude lower than the sensitivity of the sensors. The
actual system should be capable in measuring processes of the order of mW, while
applying mechanical loads and perfusing constantly with culture medium.

Figure 17. Schema of principle of the deformation    Figure 18. The deformation calorimeter's sensors
calorimeter.                                         mounted on the loading machine.

Perspective for 2010
We will perform calorimetric studies on soft polymers and hydrogels under
mechanical loading.

Laboratory of Biomechanical Orthopedics             22                                
      Bone remodeling model around a drug delivery
Collaborator: P. Abdel-Sayed
Supervisors: A. Terrier, P.Y. Zambelli, D.P. Pioletti

Total arthroplasty is a successful solution for restoring movement to damaged joints,
however the lifespan of the implants is limited, because of pathologic strain
distribution in bone inducing bone-resorption and limiting the long-term stability of
implant in bone. Currently research is being done to enhance the lifespan of these
implants by their use as drug delivery system. However, a real need of understanding
how the used drug behaves and affects bone remodeling still remains. The purpose of
the present project is to develop a 3D model, which allows numerical simulations of
the drug effect to be coupled with bone remodeling.

Results obtained in 2008
The numerical model was
implemented in Abaqus finite
element program. It includes
bone     remodeling      due     to
mechanical loadings extended
with a drug effect. The drug
effect     encompasses         the
diffusion evolution of a drug
and a supplemental stimulus as
function of drug concentration.
After implementation, the results
of the model were compared to
an in vivo study in order to validate
its predictability of bone
density evolution due to                Figure 19. Experimental (points) and model (lines) bone densities as
                                        a function of distance from implant coatings for different drug
zoledronate            locally          concentrations.
delivered in rat tibias
(Figure 19).
The implementation of the remodeling and the diffusion of the drug were successfully
achieved and reveal a large precision, less than 1% error between analytical solutions
and model predictions. Nevertheless, the experimental validation of drug effect
function has revealed that some parameters defining the role of zoledronate need to be

Perspective for 2009
We will experimentally determine the rate of drug release and the drug diffusivity of
zoledronate in order to give the best model-predictions of bone relative density.

Laboratory of Biomechanical Orthopedics            23                             
PhD thesis
    •   Quintin A. Fetal cells for intervertebral disc regeneration. Thesis EPFL #4439,
    1. Stadelmann V.A., Terrier A., Gauthier O., Bouler J.-M., Pioletti D.P.
        Prediction of bone density around orthopedic implants delivering
        bisphosphonate. J Biomechanics, 42, 1206–1211, 2009.
    2. Terrier A., Merlini F., Pioletti D.P., Farron A. Comparison of polyethylene
        wear in anatomic and reversed shoulder prostheses. J Bone Joint Surg-B, 91-
        B, 977-982, 2009.
    3. Blecha L.D., Rakotomanana L., Razafimahery F., Terrier A., Pioletti D.P.
        Targeted mechanical properties for optimal fluid motion inside artificial bone
        constructs. J Orthop Res, 27, 1082-1089, 2009.
    4. Terrier A., Sedighi-Gilani M., Roshan Ghias A., Aschwanden L., Pioletti D.P.
        Biomechanical evaluation of porous biodegradable scaffolds for revision knee
        arthroplasty. Comp Meth Biomech Biomed Eng, 12, 333-339, 2009.
    5. Quintin A., Schizas C., Scaletta C., Jaccoud S., Chapuis-Bernasconi C.,
        Gerber S., Juillerat L., Osterheld M.C., Applegate L.A., Pioletti D.P. Human
        foetal spine as a source of cells for intervertebral disc regeneration. J Cell Mol
        Med, 13, 2559-2569, 2009.
    6. Montjovent M.O, Bocelli-Tyndall C., Scaletta C., Scherberich A., Martin I.,
        Laurent-Applegate L., Pioletti D.P. In vitro characterization of immune-
        related properties of human fetal bone cells for potential tissue engineering
        applications. Tissue Engineering, 15, 1523-1532, 2009.
    7. Terrier A., Merlini F., Pioletti D.P., Farron A. Total shoulder arthroplasty:
        downward inclination of the glenoid component to balance supraspinatus
        deficiency. J Shoulder Elbow Surg, 18, 360-365, 2009.
    8. Stadelmann V.A., Hocké J., Forster V., Merlini F., Terrier A., Pioletti D.P. 3D
        strain map of axially loaded a mouse tibia: a numerical analysis validated by
        experimental measurements. Comp Meth Biomech Biomed Eng, 12, 95-100,
    9. Applegate L.A., Scaletta C,. Hirt-Burri N., Raffoul W., Pioletti D.P. Whole-
        cell bioprocessing of human fetal cells for tissue engineering of skin. Skin
        Pharmacol Physio, 22, 63-73, 2009.
    10. Ramelet A.A, Hirt-Burri N, Raffoul W., Scaletta C., Pioletti D.P., Offord E.,
        Mansourian R., Applegate L.A. Fetal cell therapy for chronic wound treatment
        and differential gene profiling compared to old skin cells. Exp Gerontology,
        44, 208–218, 2009.
    11. Stadelmann V., Terrier A., Pioletti D.P. Osteoclastogenesis can be
        mechanically-induced in the peri-implant bone. Biomedical Engineering and
        Research, 30, 10-13, 2009.

Laboratory of Biomechanical Orthopedics      24                         
Book chapter
   • Applegate L.A., Hirt-Burri N., Scaletta C., Bauen J-F., Pioletti D.P.
     Bioengineering of human fetal tissues for clinical use. In: Bioengineering:
     Principles, methodologies and applications, edited by Garcia A. and Durand
     C., Nova Science Publishers Inc, 2009.
    • Stadelmann V.A., Gauthier O., Bouler J.M., Terrier A., Pioletti D..P Prediction
       and optimization of bone density around orthopedic implants delivering
       bisphosphonate. Proc 55th Orthop Res Soc, 2009.
    • Terrier A., Leclercq V., Leyvraz P.F., Pioletti D.P. Contact pattern on the
       polyethylene insert of a mobile knee prosthesis: effect of tibial tray inclination.
       Proc 55th Orthop Res Soc, 2009.
    • Terrier A., Merlini F., Pioletti D.P., Farron A. Polyethylene wear in anatomic
       and reversed shoulder prostheses. Proc 55th Orthop Res Soc, 2009.
    • Stadelmann V., Pioletti D.P. Combined effects of zoledronate and mechanical
       stimulation in the mouse tibia. Proc 55th Orthop Res Soc, 2009.
    • Pioletti D.P., Blecha L.D., Terrier A., Zambelli P.Y., Razafimahery F.,
       Rakotomanana R. Which mechanical properties are needed for an optimal fluid
       motion inside artificial bone scaffolds? Proc 55th Orthop Res Soc, 2009.
    • Stadelmann V.A., Bianchi N.E., Ferrari S., Terrier A., Pioletti D.P. The role of
       β-arrestin in bone mechanotransduction. Proc 55th Orthop Res Soc, 2009.
    • Montjovent M.O., Bocelli-Tyndall C., Scaletta C., Scherberich A., Mark S.,
       Martin I., Applegate L.A., Pioletti D.P. Immune-related properties of human
       fetal bone cells for potential tissue engineering applications. Proc 55th Orthop
       Res Soc, 2009.
    • Quintin A., Schizas C., Scaletta C., Jaccoud S., Applegate L.A., Pioletti D.P.
       Human fetal spine cells: a potential cell source for intervertebral disc
       regeneration? Proc 55th Orthop Res Soc, 2009.
    • Seidenglanz U., Mathieu L., Zeiter S., van der Pol B., Bourban P.E., Zambelli
       P.Y., Pearce S., Bouré L., Pioletti D.P. Augmentation of bone defect healing
       using a new biocomposite scaffold (PLA/TCP). Proc 55th Orthop Res Soc,
    • Stadelmann V.A., Gauthier O., Bouler J.M., Terrier A., Pioletti D.P. Model to
       optimize the amount of drug on an implant used as drug delivery system. 34th
       Société de Biomécanique, 2009.
    • Terrier A., Leclercq V., Pioletti D.P. Jolles B.M. Total knee arthroplasty:
       posterior tilt of tibial tray. 34th Société de Biomécanique, 2009.
    • Terrier A., Kochbeck S.H., Merlini F., Gortchacow M., Farron A., Pioletti D.P.
       Reverse shoulder arthroplasty: compression screw force. 34th Société de
       Biomécanique, 2009.
    • Terrier A., Merlini F., Farron A., Pioletti D.P. Reverse shoulder arthroplasty:
       polyethylene wear. 34th Société de Biomécanique, 2009.
    • Terrier A., Kochbeck S.H., Merlini F., Pioletti D.P., Farron A. Baseplate
       compression screw force of a reversed shoulder prosthesis. Inter Soc
       Biomechanics, 2009.

Laboratory of Biomechanical Orthopedics      25                         
    • Gortchacow M. Saxena S., Wettstein M., Pioletti D.P., Terrier A. Measuring
       micromotion around a loaded hip stem using µCT imaging. Inter Soc
       Biomechanics, 2009
    • Roshan-Ghias A., Terrier A., Bourban P.E., Pioletti D.P. Effect of early loading
       of bone scaffolds on bone formation in vivo. Int Conf Tissue Engineering,
    • Borges A.C., Bourban P.E., Pioletti D.P., Månson J.-A. E. Replacement of the
       nucleus pulposus by a composite hydrogel. 22th Europ Conf Biomat, 2009.
    • Delabarde C., Bourban P.E., Plummer C.J.G., Pioletti D.P., Månson J.-A.E.
       Effect of surface treatments of PLLA films on bone cell behaviour. 22th Europ
       Conf Biomat, 2009.
    • Roshan-Ghias A., Terrier A., Bourban P.E., Pioletti D.P. Morphological study
       of bone formation in tissue engineering scaffolds: an in vivo micro-CT study.
       22th Europ Conf Biomat, 2009.
    • Gortchacow M., Saxena S., Wettstein M., Pioletti D.P, Terrier A. Feasibility of
       measuring 3D micromotions on human hip stems with μCT imaging. 22th
       Europ Conf Biomat, 2009.
    • Krattinger N., Laurent-Applegate L.A., Caverzasio J., Pioletti D.P. Influence of
       culture condition on the proliferation of human fetal for bone tissue
       engineering application. 22th Europ Conf Biomat, 2009.
    • Darwiche S., Applegate L.A., Pioletti D.P., Raffoul W. A multidisciplinary
       approach to quantitatively assess cutaneous reconstructions and skin grafts.
       13th Europ Burns Association Congress, 2009.
    • Krattinger N, Applegate L.A., Pioletti D., Caverzasio J. Effects of culture
       conditions on the proliferation and differentiation capacities of human fetal
       bone cells. ECM, 2009.
    • Vogel A., Pioletti D.P. A polyvalent dissipation potential with interpretable
       viscous material parameters. International Symposium on Plasticity, 2009.
    • Roshan-Ghias A., Terrier A., Bourban P.E., Pioletti D.P. Effect of loading on
       bone formation inside bone scaffolds: A longitudinal study using micro
       computed tomography. 3rd Switzerland-Japan Workshop on Biomechanics,
    • Stadelmann V. A., Gauthier O., Terrier A., Pioletti D.P. Prediction and
       optimization of bone density around orthopedic implants delivering
       bisphosphonate. 3rd Switzerland-Japan Workshop on Biomechanics, 2009.
Invited talk
    • “Control of bone formation around an implant used as drug delivery system”,
       5th Modern Drug Discovery & Development Summit, San Diego, 2009.
    • “Biomechanical considerations in the development of a cellular biocomposite
       for bone tissue engineering application”. 22th Europ Conf Biomat,
       ESBiomech session, 2009.
    • “Development of an artificial bone scaffold with high mechanical properties
       using a biocomposite and fetal cells”, Department of Biomedical Engineering,
       University of California San Diego, La Jolla, February 2009.
    • Keynote Speaker: “Artificial bone scaffold performance can be enhanced by
       biomechanical analysis”, International Conference on Tissue Engineering,

Laboratory of Biomechanical Orthopedics    26                       
         ECCOMAS, Leiria, Portugal, 2009.
    •   Keynote lecture “Biomechanical considerations can serve as design rules in the
         development of bone tissue engineering scaffold”, Société de Biomécanique,
         Toulon, 2009.
    •   “Dissipative phenomena in biological tissues”, Advances in the Theory of
         Control, Signals, and Systems, with Physical Modeling, Chemical and Life
         Science Workshop Bernouilli Center, EPFL, 2009.
    •   “Consideration of fluid motion in the design of biomaterials”, 3rd Switzerland-
         Japan Workshop on Biomechanics, Engelberg, Switzerland, 2009.
    •   “Biomechanical aspects in the development of bone tissue engineering”,
         ESF/EORS Workshop on stem cells for bone regeneration, Bologna, Italy,
    •   “Bio-ingénierie: quoi de neuf en orthopédie?”, Opening lecture, 19ième
         Journée Romande des Orthopédistes, Montreux, Suisse.
    •   “Biomechanics and bone tissue engineering: how to combine them?”, EFORT,
         EORS session, Vienna, Austria, 2009.

    •    La biomécanique du record du monde du 100 m, TSR1, TJ 19h30, 2009.
    •    La biomécanique dans les performances sportives, RSR1 “Journal des sports”,

The studies are supported by grants from:
   • Swiss National Science Foundation;
   • AO Foundation;
   • Fondation Lémanique pour la Recherche sur le Tissu Osseux;
   • Fondation Fernando et Rose Inverni-Desarzens;
   • Fondation Famille Sandoz ;
   • Fondation S.A.N.T.E.
and industrial financial supports by: Stryker; Symbios; Tornier.

Laboratory of Biomechanical Orthopedics      27                      
Address:        EPFL/STI/IBI/LBO
                Station 15
                1015 Lausanne

Tel:            +41 21 693 83 43

Fax:            +41 21 693 86 60


Laboratory of Biomechanical Orthopedics      28

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