3rd MuscleTech Network Workshop. Muscle injuries and repair: Current trends in research.

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2 3rd MuscleTech Network Workshop. Muscle injuries and repair: Current trends in research. CONCLUSIONS AND CLOSING REMARKS Dr. Carles Pedret

3 MUSCLE AND TENDON WORKSHOP HEALTH AND GENERAL POPULATION SPORTS MEDICINE ORTHOPEDICS MUSCLE AND TENDON MORE KNOWLEDGE MORE APPLICATIONS RESEARCH!!! TISSULAR ENGINEERING

4 KEY NOTE LECTURES

5 CHALLENGES IN MUSCLE-TENDON RESEARCH AND IMPLEMENTATION TO CLINICAL PRACTICE Role of the massage if applied in the correct time, intensity and frequency improves significantly the muscle regeneration. Neutrophils role inhibiting neutros we also improve regeneration

6 BIOLOGICAL APPROACHES TO IMPROVE MUSCLE HEALING inflammation degeneration regeneration fibrosis TGF-β1 1 w 2 w 3 w

7 BIOLOGICAL APPROACHES TO IMPROVE MUSCLE HEALING Focus on blocking fibrosis to improve regeneration decorina, relaxina losartan NSAIDs regeneration retard, more fibrosis, difficult muscle cells differentiation. Improve angiogenesis neuromusc. electric stimulation, exercise, massage

8 EVALUATING STRENGTH TESTS AS ELEMENTS OF INJURY PREDICTION

9 Basic for the prevention knowing the injury mechanism. A core stability training program reduces the re-injury risk (hamstrings, lumbar spine..) In the future find the optimal duration of stretching and training programs.

10 Important role of the aponeurosis as an injury factor further studies.

11 INJURIES IN THE ADOLESCENT STAGE

12 CLINICAL PROGNOSTIC VALUES IN HAMSTRING INJURIES Past history of hamstring injury is the main risk factor for the next injury. Injury involving proximal free tendon, proximity of the injury to the ischial tuberosity, increased length and cross-sectional area of injury, flexibility of the hamstring. Defining the severity of the injury enable us to assess the expected return to play timescale which is important in guiding rehabilitation and in team planning.

13 CLINICAL PROGNOSTIC VALUES IN HAMSTRING INJURIES Future trends specific exercises for each hamstring muscle

14 IMPROVING HEALTH THROUGH BETTER MUSCLE HEALTH After a life long aerobic exercise significantly higher VO2 max Quadriceps strenght Enzyme activity Gene expression (except myostatin) Muscle fiber type (type 1) Age produces sarcopenia can long life weight training attenuate sarcopenia??

15 PROGNOSTIC VALUE OF ULTRASOUND AND MRI IN MUSCLE AND TENDON INJURIES

16 HIGH-SPEED RUNNING OR STRETCHING TYPE OF HAMSTRING INJURIES MAKES A DIFFERENCE TO MRI FINDINGS High speed running type more freq. (x2) long head of the BF!! (18-21 RTP days) Stretching type higher RTP (85-96 days) High speed stretching type (soccer ) Slow speed stretching type (dancers ) Reinjuries can be avoided knowing the injury type, the exact location and the size.

17 COST-EFFECTIVE PREVENTION OF LATERAL ANKLE INJURY Injuries to the lateral ankle ligaments constitute 15% to 45% of all sports related Injuries. Reinjuries 10-73% Early return to sport & poor rehabilitation program met with a high risk of reinjure Athletes with a grade I or II lateral ankle sprain are at higher risk of experiencing a re injury

18 LONGITUDINAL STUDIES OF HAMSTRING MUSCLE INJURIES IN ATHLETES MRI allows us to exactly locate the injury (BF, ST, SM ), the size of the injury and the histopathologic type (myofascial, tendinous ). Knowing all of this information specific treatments and prevention protocols would be used goal of the study

19 UPDATE IN REGENERATIVE THERAPIES IN THE MUSCLE AND TENDON

20 REGENERATIVE MEDICINE BASED ON MUSCLE STEM CELLS MDSC reduces scar tissue formation and induces neoangiogenesis. One of the points is to try to differentiate, target and isolate SC basing in their capacity to tolerate stress. All the organs that generate SC have blood vessels (probably the source of MDSCs)

21 REGENERATIVE MEDICINE BASED ON MUSCLE STEM CELLS MUSCULAR DISTROPHY (MD) SC decrease in number and function with aging (exhaustion SC). MDSC display a better regeneration capacity than other differentiated SC (myoblasts) due to the capacity to stress resistance and paracrine effects. MD represents a model of accelerated muscle with exhaustion SC future investigation.

22 MECHANICAL AND BIOLOGICAL INTERACTION BETWEEN MUSCLE CELLS AND THE EXTRACELLULAR MATRIX The muscle fiber are involved in connective tissue that allows the forces distribution within the muscle not only longitudinally. There are some muscle fibers that only stay in the ECM that gives the muscle more tolerance to stress.

23 There are mechanical links of ECM between muscle fibers in all space directions. ECM is highly adaptable but its properties is poorly understood demonstrated in cerebral palsy (fibers increase stiffness and EMC decrease stiffness)

24 REGENERATIVE THERAPIES IN THE MUSCLE AND TENDON Available data are lacking to allow definitive conclusions on the use of biomaterials for tendon adaptation. PRP benefits remain unproven to date but we know that it has very low risk. Ethical problems. The results until now are promisingly but still further investigations are needed. There is still a mountain to climb

25 CLINICAL PRACTICE GUIDE OF TENDON INJURIES

26 CONNECTIVE TISSUE, FIBROBLASTS AND MYOFIBROBLASTS Prolonged loading during years produce modifies to the muscle and tendon tenocyte response maybe adaptation of the tissue. Changes in fibril diameter are correlated with changes in collagen I and III inverse relation between type III collagen and the developed tendon. Type III collagen may have role in the fibrillogenesis.

27 Injured tendon healing phase + disorganization of the matrix. Eccentric or Concentric?? HSRT (slow movement 3sec. concentric + 3sec. eccentric) Higher collagen turnover/synthesis in HSRT. Adhesions reduce function pain eccentric exercises break adhesions. Consider ultrasound-guided high volume injections for the treatment.

28 PREVENTION AND MANAGEMENT OF TENDON INJURIES Warm-up program to improve strength and neuromuscular control could really help to prevent muscle injuries (FIFA 11+) Tendon is there a metabolic disorders? Genetic predispose? probably yes In tendon it is not known where the pain originates from neither why and how the therapeutic modality works.

29 Key point Prevention injuries specially in the young age. Respect the injury biology and the injury is going to respect you

30 UPDATE IN MUSCLE AND TENDON INJURY AND REPAIR BIOMARKERS

31 THE MYSTERY OF POPPING SARCOMERES Sarcomeres do not pop (overextension) because they are unstable. Sarcomere popping may be a protective measure rather than a sign of injury and weakness Sarcomere popping does not represent structural or functional damage Muscles are dynamically stable at all lengths

32 WHAT PROCESSES ARE TAKING PLACE IN THE HEALING TENDON? Major structural and molecular changes in chronic tendinopathy increase collagen I and III, TGF-1, VEGF, PDGFR Healing tendon TGF-β, GH modulate the collagen synthesis. VEGF increased PGE2 and inflammatory cytokines play an important role in wound healing IL-6 a potential role as growth factor

33 CELLULAR AND TRANSCRIPTIONAL CHANGES AFTER MUSCLE INJURY Earliest events associated with injury are mechanical and based primarily on sarcomere strain The use of muscles with knocked out or modified cytoskeletal proteins give insights into load bearing and transmission in skeletal muscle

34 IN THE SEARCH OF HUMAN MODELS OF MUSCLE DAMAGE AND REPARATION Understanding the molecular mechanism involved in muscle reparation it will be easiest to elaborate strategies to prevent muscle damage and accelerate reparation and functional recovery.

35 TAKE IT HOME There are very promising muscle and tendon workgroups at this moment not just in sports medicine also in health. We are in preliminary phases and we need to focus efforts to find useful and applicable results MTN 2012, 2013 Studies and results need further scientific evidence.

36 TAKE IT HOME Share Information between work groups. Cooperate in studies. Write scientific articles. We started to have results, but there is still a lot of work to do.

37 THANK YOU ALL