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interventions or define stimuli that produce a functional outcome.

Therapeutic measures based on information of muscle plasticity

would thus offer considerable socioeconomic potential for

musculoskeletal medicine, but its application in the management

of healthcare is underdeveloped today.

Repair mechanisms after rupture of the anterior

cruciate ligament

As a joint, the knee exerts the important task of translating and

potentialising forces being produced in the upper, large thigh

muscles via the lever arm of the femoro-patellar articulation. This

function is essential to counteract the forces of gravity through the

extension of the knee. On the downside, however, the knee joint is

exposed to particularly high rates of mechanical stress. This may

damage anatomical structures that stabilise the knee joint if the

resulting mechanical strain exceeds the typical safety factor for

musculoskeletal tissues.

This is especially true for the mechanical impact on ligaments that

operate in the lateral direction, such as the anterior cruciate

ligament (ACL) and medial patella-femoral ligament. Their integrity

is challenged by biomechanical vectors that operate in transverse

directions to the main movement of the knee joint. This often

occurs with intense physical activity in sports and during manual

labour and may lead to tendon rupture. This is a relatively frequent

condition affecting one in 1,750 individuals each year. Because it

renders the function of the affected knees unstable, repair of the

damaged soft tissue is strongly indicated. This requires

orthopaedic surgery and subsequent physical procedures to

support the functional recovery of the reattached ligament and

connected muscle as it is weakened due to the prior injury and

enhanced catabolism during unloading. Typically this is initiated

by resistive types of exercise. The dose-effect relationships for

musculoskeletal adaptations with rehabilitation, which define the

therapeutic success of orthopaedic surgery, are not well defined.

Towards this end we pursue an investigation to define the time

course of molecular and cellular adaptations in a major knee

extensor muscle with exercise-based rehabilitation subsequent to

surgical repair of the ruptured ACL. This study is inspired by our

results showing that eccentric types of endurance activity, such as

that seen with downhill sports activities (skiing), represent a

potent intervention to strengthen the musculotendinous structures

that operate on the knee

joint.We

expect that our study will

provide important information as to the quality and effect size of

the rehabilitation for the deconditioned muscle and knee function.

Focus on rotator cuff disease

The rotator cuff is a complex group of skeletal muscles which

facilitate shoulder function. This involves important actions such as

internal and external rotation as well as the abduction of the arm.

Full or partial tears of rotator cuff tendons are a relatively frequent

condition affecting a considerable portion of the population.

Ageing-associated factors and injury represent the major cases of

the disease. Thereby current numbers indicate that 40% of

subjects above 60 years of age demonstrate tears of the rotator

cuff. This severely complicates daily activities as it renders the

accentuation of the upper extremity in one or more direction hard

to impossible. If left untreated, shoulder function is permanently

affected because the detached muscle degenerates by shrinkage

of muscle cells and their conversion into fat tissue. Eventually this

limits kinematics of respective joints, which has the ultimate

consequence in the degeneration of the glenohumeral joint. At

this point no other option remains than to surgically replace the

joint with an expensive endoprosthesis to reinstate limb function.

Surgical interventions aimed at repairing the affected shoulder

muscle involve the reattachment of the ruptured tendon to the

bone via an anchor. Thereby the prevention of adipogenic and

atrophic processes in the detached muscle is a priority to warrant

optimal surgical repair of the ruptured muscle-tendon unit.

Towards improving the therapy of rotator cuff disease, we

investigate the time course of molecular and cellular alterations

in animal models of the ruptured rotator cuff. The aim is to map

the mechano-regulated pathobiological process and risk factors

of muscle degeneration, which contributes to the healing of

muscle-tendon complex. Specific emphasis is put on testing the

effectiveness of pharmacological compounds targeting the

degradation of structural anchors of the contractile apparatus in

muscle fibres.

The knowledge is integrated in a clinical trial in which we

characterise morphological and genetic biomarkers of the healing

response of rotator cuff muscle after surgical repair of the

detached tendon. This is motivated by the reported contribution of

heritable factors to the healing of the reattached rotator cuff. The

aim is to reintegrate the gathered knowledge into personalised

surgical approaches and therapies that more efficiently prevent

detractions in shoulder muscle function in critical responder

groups (Fig. 2).

Professor Martin Flück, PhD

Laboratory for Muscle Plasticity

University Hospital Balgrist

tel :

+41 (0) 44 386 3791

mflueck@research.balgrist.ch http://www.balgrist.ch/en/Home/Research-and- Education/Orthopaedics/Muskelplastizitaet.aspx www.horizon2020projects.com

H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L

I S S U E S E V E N

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P R O F I L E

S O C I E TA L C H A L L E N G E S : H E A L T H & W E L L B E I N G

Fig. 2 Research approach scheme of the conceptual path of the

research strategy of our integrated studies towards improved

treatment of the orthopaedic patient