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See detailPlatelet-rich plasma and tendons healing: rat model
Kaux, Jean-François ULg; Drion, Pierre ULg; Colige, Alain ULg et al

in Biomedica Life Science Summit (2011, April 07)

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See detailInfluence sur le tissu tendino(-musculaire) du mode de contraction en entraînement : modèle animal
Kaux, Jean-François ULg; Drion, Pierre ULg; Croisier, Jean-Louis ULg et al

in Julia, Marc; Hirt, Daniel; Croisier, Jean-Louis (Eds.) et al Tendon et jonction tendino-musculaire - De la biomécanique aux applications thérapeutiques (2011)

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See detailPlatelet-rich plasma (PRP) and tendon healing: animal model
Kaux, Jean-François ULg; Drion, Pierre ULg; Renouf, Julien et al

in British Journal of Sports Medicine (2011, February), 45(2), 1

Introduction: The tendon is a tissue which does not heal easily. Recently, several studies have demonstrated the positive effects of platelets on the healing process of tendons. A local injection of ... [more ▼]

Introduction: The tendon is a tissue which does not heal easily. Recently, several studies have demonstrated the positive effects of platelets on the healing process of tendons. A local injection of platelet–rich plasma (PRP), which releases in situ many growth factors, has the potentiality to enhance the tendon healing process. The aim of our experiment was to ascertain by an original mechanical measure whether the use of PRP was of interest for accelerating the healing process of rats’ Achilles tendons after surgical induced lesion. Methods: A 5mm defect was surgically induced in 90 rats’ Achilles tendon. Rats were divided into 2 groups of 45: (A) control (no treatment) and (B) PRP treatment. Rats of group B received a PRP injection in situ after the surgery. Afterwards, rats of both groups were placed in their cages without immobilization. After 5, 15 and 30 days, 10 traumatized Achilles tendons of each group were dissected and removed. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. After that, transcriptomic analyses were made on the tendon samples, to study the expression of type III collagen, matrix metalloproteases and tenomodulin. A hydroxyproline dosage was done to quantify the collagen in the tendon during its healing process. Tendons of the 15 remaining rats of each group were subjected to a histological study, respectively at day 5, 15 and 30 (5 rats for each time). Results: We demonstrated that the force necessary to induce tendon rupture during biomechanical tensile test study was greater for tendons which had been submitted to an injection of PRP compared to the control group: +19% (day 5), +30% (day 15) and +43% (day 30). Histological study showed that PRP could enhance cells proliferation, angiogenesis and collagen organisation. Our biochemical analyses did not explain beneficial effects of PRP. Indeed, there was no significant difference neither between the expression of different studied genes, nor in the quantity of hydroxyproline between both groups. Conclusion: This experimentation has shown that a PRP injection could accelerate the tendons healing process and improve its quality. [less ▲]

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See detailExperimental characterization and elasto-plastic modeling of the quasi-static mechanical response of TA-6 V at room temperature
Gilles, Gaëtan ULg; Hammami, Walid ULg; Libertiaux, Vincent ULg et al

in International Journal of Solids & Structures (2011), 48(9), 12771289

The paper presents an experimental study of the quasi-static deformation behavior of a TA-6V in sheet form. To quantify the plastic anisotropy and the tension-compression asymmetry of this material at ... [more ▼]

The paper presents an experimental study of the quasi-static deformation behavior of a TA-6V in sheet form. To quantify the plastic anisotropy and the tension-compression asymmetry of this material at room temperature, monotonic tensile and compressive tests were carried out on specimens cut out along several orientations in the plane of the sheet. It was observed that although the tensile flow stress anisotropy is very mild, the Lankford coefficients’ anisotropy is very pronounced. To describe the observed mechanical response an elastic/plastic approach was used. Yielding was described using a family of yield criteria that account for strength differential effects and allow an improved description of the anisotropy and its evolution through multiple linear transformations. Comparisons between uniaxial monotonic data and FE simulations using the model show a very good agreement. [less ▲]

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See detailTendon lesion and platelet-rich plasma (PRP) injection: rat model
Kaux, Jean-François ULg; Drion, Pierre ULg; Renouf, Julien et al

in Annual Congress of the RBSPRM (2010, December 03)

Introduction: For a few years, the positive effect of platelets on the healing process of different tissues (skin, bones...) was demonstrated. In fact platelets contain lots of growth factors which can be ... [more ▼]

Introduction: For a few years, the positive effect of platelets on the healing process of different tissues (skin, bones...) was demonstrated. In fact platelets contain lots of growth factors which can be release locally and enhance the healing process. Thus the aim of our experiment was to ascertain by an original mechanical measure whether the use of PRP was of interest for accelerating the healing process of rats’ Achilles tendons after surgical induced lesion. Methods: Ninety rats’ Achilles tendons were sectioned. Forty-two rats beneficed of a PRP injection in situ. After 5, 15 and 30 days, 15 rats of both groups were euthanized after tendon sampling which were immediately submitted to a biomechanical tensile test until tendon rupture, using an original method of measurement (“cryo-jaw”). Histological and biochemical analyses were made as well as a quantification of collagen with an original procedure (quantification of the “greys” on histological cross-sections). Results: Tendons in the PRP group were more resistant to rupture than those in the control group. Histological findings showed in this group an increase of collagen proliferation and better collagen fibres reorganization. However, we did not find any biochemical difference neither in term of encoding gene expression for type III collagen, matrix metalloprotease 9 and tenomodulin. Conclusion: Our animal study demonstrated that an injection of PRP could accelerate the tendons healing process and improve its quality. [less ▲]

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See detailIntrinsic modification of tendon structure after concentric or excentric training
Kaux, Jean-François ULg; Drion, Pierre ULg; Besançon, Benoît et al

Poster (2010, November 25)

Introduction: It is well known that eccentric training is a successful way of treating chronic tendinopathy. Although clinical results are very positive, beneficial morphological and histological effects ... [more ▼]

Introduction: It is well known that eccentric training is a successful way of treating chronic tendinopathy. Although clinical results are very positive, beneficial morphological and histological effects have not yet been elucidated. The aim of our experiment was to determine if there exist any intrinsic modifications in a tendon trained in concentric or eccentric modes, in a rat model, using an original method of measurement (cryo-jaws). Methods: 18 rats were divided into 3 groups: 6 for the control group, without physical restraint; 12 for a training of1 hour, 3 times a week, for 5 weeks, at a speed of 17m/min (1km/h), on a inclined treadmill: 6 rats running uphill at +15° for the concentric effort (group C) and 6 rats running downhill at -15° for the eccentric effort (group E). After this training period, the Achilles, patellar and tricipital tendons of both limbs were surgically removed in all 18 rats. Tendons taken from five rats of each group were subjected to a tensile test up to rupture using a “cryo” jaw. Tendons of the remaining rat of each group were subjected to a histological study. Results: The results showed significant changes in group E only: (1) an increase of the force required to rupture the patellar and tricipital tendons; (2) an improvement of the ratio between the force necessary to rupture the tricipital tendon and the body mass of the rats; (3) an increase of the surface area of the section of the tricipital tendon. No significant change was observed as far as constraint was concerned between groups. Histologically, we saw, in the group E, more peripheral blood vessels and a greater proportion of collagen. Conclusion: This study showed that the mechanical properties of tendon tissue are enhanced by eccentric training. Tendons become stronger, the amount of collagen increases and there is probably more interaction between collagen fibers (mechanotransduction). [less ▲]

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See detailTendon lesion and VEGF-111 injection
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent ULg et al

Poster (2010, November 25)

Introduction: Tendon lesion is one of the most frequent pathology in sports and by physical workers. This pathology often becomes chronic. For this reason, it is of interest to develop new treatments ... [more ▼]

Introduction: Tendon lesion is one of the most frequent pathology in sports and by physical workers. This pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Injection of platelet-rich plasma (PRP) seems to be a promising one by releasing growth factors (GF) locally. Among all the GF released by activated platelets, the vascular endothelial growth factor-A (VEGF-A) is known to induce positive effects on vascular function and angiogenesis, and could be implicated in the healing process of tendons. Recently, a novel VEGF-A isoform was identified, the VEGF-111, a biologically active and proteolysis-resistant VEGF-A isoform, also known to present beneficial effects on ischemic diseases. This prompted us to evaluate whether VEGF-111 would have a therapeutic interest within the framework of the tendon pathology. Methods: 60 Rats were divided into 2 groups: A: control (no injection), B: VEGF-111 treatment. A 5mm defect was surgically induced in rat Achilles tendon after resection of plantaris tendon. Rats received a local injection of VEGF-111 (100ng) in situ after the surgery and were placed in their cages without immobilization. After 5, 15 and 30 days, the traumatized Achilles tendons of 10 rats of both groups were removed and dissected during their healing process. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. Rats were then euthanized. Statistical analyses were made with an ANOVA. Values are significant when p-value is below 0.05. Results: Our results showed that the developed force necessary to induce tendon rupture during biomechanical tensile test was greater for tendons which had received an injection of 100ng of VEGF-111. These results were already noticed from day 5 onwards. The ratio between force and weight increased with time in both groups, but this ratio was greater for tendons which had been submitted to an injection of VEGF111. The surface area of the section of the tendons increased between 5 and 15 days followed by a stabilization. After 30 days, sections in both groups were similar. Thus, the constraint was similar after 5 and 15 days but was better for VEGF111 group after one month. Discussion - Conclusion: This experimentation has shown that a 100ng injection of VEGF-111 stimulated tendon healing process as suggested by the increased force needed to break tendons during its healing process and the increased of constraint in comparison with the control group. Other experimentations with different concentration of VEGF111 are now in process. Acknowledgement : This experimentation was partially financed by “Standard de Liège 2007” and “Lejeune-Lechien 2008” grants. [less ▲]

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See detailTendon lesion and platelet-rich plasma (PRP) injection
Kaux, Jean-François ULg; Drion, Pierre ULg; Renouf, Julien et al

Poster (2010, November 25)

Introduction: For a few years, the positive effects of platelets on the healing process of different tissues (skin, bones...) were demonstrated. In fact platelets contain lots of growth factors which can ... [more ▼]

Introduction: For a few years, the positive effects of platelets on the healing process of different tissues (skin, bones...) were demonstrated. In fact platelets contain lots of growth factors which can be release locally and enhance the healing process. Thus the aim of our experiment was to ascertain by an original mechanical measure whether the use of PRP was of interest for accelerating the healing process of rats’ Achilles tendons after surgical induced lesion. Methods: A 5mm defect was surgically induced in 90 rats’ Achilles tendon. Rats were divided into 2 groups of 45: (A) control (no treatment) and (B) PRP treatment. Rats of group B received a PRP injection in situ after the surgery. Afterwards, rats of both groups were placed in their cages without immobilization. After 5, 15 and 30 days, 10 traumatized Achilles tendons of each group were dissected and removed. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. After that, transcriptomic analyses were made on the tendon samples, to study the expression of type III collagen, matrix metalloproteases and tenomodulin. A hydroxyproline dosage was finally realised to quantify the collagen in the tendon during its healing process. Tendons of the 15 remaining rats of each group were subjected to a histological study, respectively at day 5, 15 and 30 (5 rats for each time). Results: We demonstrated that (1) the stress (F) during biomechanical tensile test up to tendon rupture was significantly greater for tendons which had been submitted to an injection of PRP compared to the control group; (2) the surface (S) area of the section of the tendon was greater in the PRP group during the 15 first days, but this section was similar after 30 days in the 2 groups; (3) the ration F/weight of the rat was significantly greater in the PRP group at each time; (4) constrain was similar after the 15 first days but was significantly greater in the PRP group after 30 days. Histological study showed that PRP could enhance cells proliferation, angiogenesis and collagen organisation. Our biochemical analyses did not explain beneficial effects of PRP. Indeed, there was no significant difference between the expressions of different studied genes. Conclusion: Our animal study demonstrated that an injection of PRP could accelerate the tendons healing process and improve its quality. [less ▲]

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See detailInfluence du mode de contraction sur le tendon : modèle animal
Kaux, Jean-François ULg; Drion, Pierre ULg; Besançon, Benoît et al

in 3ème Congrès Commun SFMS - SFTS (2010, October 01)

Introduction : Les tendinopathies sont fréquentes et touchent aussi bien les membres supérieurs que les membres inférieurs. La rééducation excentrique constitue une thérapeutique de choix dans le ... [more ▼]

Introduction : Les tendinopathies sont fréquentes et touchent aussi bien les membres supérieurs que les membres inférieurs. La rééducation excentrique constitue une thérapeutique de choix dans le traitement des tendinopathies. Malgré les résultats favorables en clinique, les effets morphologiques et biochimiques n’ont pas encore été élucidés. Matériel et méthodes : Dix-huit rats de souche Sprague-Dawley adultes ont été répartis en trois groupes : 6 témoins (groupe T) qui ne sont soumis à aucune contrainte physique ; 6 soumis à un effort concentrique (groupe C), course en montée ; 6 soumis à un effort excentrique (groupe E), course en descente. Les 12 rats des groupes C et E ont dû courir sur un tapis roulant incliné à +15° (groupe C) ou -15° (groupe E) à une vitesse de 17m/min (1km/h) pendant une heure à raison de trois séances par semaine pendant 5 semaines. Au terme de l’entraînement, les tendons achilléens, rotuliens et tricipitaux ont été prélevés bilatéralement. Les tendons de cinq rats de chaque groupe ont bénéficié d’une évaluation biomécanique (test de traction à l’aide de mors type « cryo-jaws »). Les tendons du sixième rat de chaque groupe ont permis l’étude histologique (coloration à l’hématoxyline-éosine et trichrome de Masson). Résultats : Le groupe E présente une augmentation de la tension de rupture des tendons rotuliens (29 ,5% ; p=0,047) et tricipitaux (72% ; p=0,018), une amélioration du rapport Force/Masse pour le tendon tricipital (54% ; p=0,043) ainsi qu’une augmentation de la section tendineuse tricipitale (74% ; p=0,008). Aucune variation pour aucun des tendons entre les groupes n’est relevée pour le paramètre contrainte (=Force/Section). Histologiquement, les tendons du groupe E se caractérisent par une plus grande quantité de vaisseaux sanguins périphériques ainsi qu’une plus grande proportion de collagène. Conclusion : Cette étude démontre que les propriétés mécaniques du tendon sont améliorées après un entraînement excentrique. Le tendon plus résistant augmente sa quantité de collagène et probablement les interactions entre les fibres de collagène. [less ▲]

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See detailInjection de concentrés plaquettaires et régénération tendineuse : modèle animal
Kaux, Jean-François ULg; Drion, Pierre ULg; Renouf, Julien et al

in 3ème Congrès Commun SFMS - SFTS (2010, October 01)

Introduction : La régénération tendineuse en traumatologie du sport demeure un processus actuellement difficile à gérer et de nouvelles voies thérapeutiques sont en cours d’exploration. La littérature ... [more ▼]

Introduction : La régénération tendineuse en traumatologie du sport demeure un processus actuellement difficile à gérer et de nouvelles voies thérapeutiques sont en cours d’exploration. La littérature récente fait état d’effets bénéfiques sur la régénération tendineuse de concentrés plaquettaires (platelet-rich plasma ou PRP), administrés in situ, dus au relargage de facteurs de croissance par activation des plaquettes et à leur activité stimulante au cours de la cicatrisation. Dès lors, nous avons souhaité tester l’effet bénéfique de ce traitement sur des rats préalablement lésés au niveau de leur tendon d’Achille. Matériel et Méthode : Une section unilatérale du tendon d’Achille a été réalisée chez 60 rats Sprague Dawley adultes. De ces 60 rats, 30 ont subi une cicatrisation naturelle (rats contrôles) et 30 rats ont bénéficié d’une injection in situ de PRP le jour de la lésion. Diverses études biomécaniques, biochimiques et histologiques ont été réalisées sur ces tendons d’Achille en cours de cicatrisation à respectivement J5, J15 et J30 après lésion. Dix rats supplémentaires ont servi de témoins sains (sans lésion tendineuse). L’étude biomécanique appréciait la résistance maximale des tendons à la traction à l’aide de mors type « cryo-jaws ». L’étude histologique évaluait l’évolution cellulaire pendant la phase de cicatrisation. L’analyse transcriptomique étudiait l’expression de gènes codant pour le collagène de type III, les métalloprotéases matricielles (MMP-9) et la ténomoduline (TNMD), ainsi qu’un dosage d’hydroxyproline permettant d’évaluer la quantité de collagène présente dans le tendon au cours de la cicatrisation. Résultats : L’étude biomécanique démontre la meilleure résistance des tendons traités avec du PRP par rapport aux tendons contrôles à J5 (+19%), J15 (+30%) et significativement à J30 (+43%). L’étude histologique suggère qu’une injection de PRP stimule la prolifération cellulaire, favorise l’organisation tissulaire, stimule l’angiogenèse et la réorganisation architectural du collagène. L’étude biochimique ne permet pas d’expliquer les effets bénéfiques puisqu’il n’y a pas de différence dans l’expression des gènes des différentes molécules matricielles (collagène de type III, MMP-9 et TNMD) ni dans la quantité d’hydroxyproline qui s’accroit au cours du temps de la cicatrisation de façon similaire dans les deux groupes. Conclusion : L’injection de PRP améliore et accélère la cicatrisation tendineuse et augmente la résistance aux contraintes mécaniques du tendon en cours de cicatrisation. [less ▲]

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See detailLe VEGF-111 comme nouvel outil thérapeutique des lésions tendineuses
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent ULg et al

in 3ème Congrès Commun SFMS - SFTS (2010, September 30)

Introduction : Les lésions tendineuses sont très fréquentes en traumatologie du sport et deviennent fréquemment chroniques. Pour ces raisons, de nouvelles thérapeutiques sont en cours de développement ... [more ▼]

Introduction : Les lésions tendineuses sont très fréquentes en traumatologie du sport et deviennent fréquemment chroniques. Pour ces raisons, de nouvelles thérapeutiques sont en cours de développement. Les injections de concentrés plaquettaires (platelet-rich plasma ou PRP) semblent constituer en ce sens une voie encourageante. Elles agissent par libération locale de divers facteurs de croissance parmi lesquels le VEGF-A (vascular endothelial growth factor-A), connu pour induire un effet positif sur la fonction vasculaire et l’angiogenèse, serait impliqué dans le processus cicatriciel des tendons. Récemment, une nouvelle isoforme du VEGF-A a été identifié : le VEGF-111. Celui-ci est une isoforme biologiquement active du VEGF-A, résistant à la protéolyse et aussi connu pour présenter un effet bénéfique sur les pathologies ischémiques. Pour ces raisons, nous avons pensé que le VEGF-111 pourrait avoir un intérêt thérapeutique pour les pathologies tendineuses. Matériel et méthode : 60 rats de souche Sprague-Dawley adultes ont été séparés en 2 groupes (A: groupe contrôle sans traitement et B: groupe traité par une injection de VEGF-111). Chez ces rats, un défaut de 5mm dans le tendon d’Achille a été réalisé après résection du tendon du plantaire grêle. Les 30 rats du groupe B ont alors bénéficié d’une injection in loco de 100ng de VEGF-111. Les rats ont été euthanasiés par groupe de 20 (10 du groupe A et 10 du groupe B) respectivement à J5, J15 et J30 et le tendon d’Achille en cours de régénération a été disséqué et prélevé. Une étude biomécanique de traction jusqu’à rupture a été réalisée à l’aide de mors type « cryo-jaw ». Résultats : L’analyse de nos résultats montre que la force nécessaire pour rompre le tendon lors du test de traction, était plus importante pour les tendons du groupe B. Ces résultats peuvent être observés dès le 5ème jour. Le rapport entre la force et la masse corporelle du rat augmente dans les 2 groupes avec le temps, mais cette augmentation est plus importante pour les tendons du groupe B. La surface de section du tendon de groupe B s’accroit plus rapidement entre les jours 5 et 15 et ensuite se stabilise. Après 30 jours, les sections tendineuses sont similaires dans les 2 groupes. Enfin, dans le groupe B, les contraintes nécessaires pour obtenir la rupture du tendon, en tenant compte de l’accroissement de sa section, sont similaires entre les jours 5 et 15 et augmentent après un mois. Conclusion : Cette expérience a démontré qu’une injection de 100ng de VEGF-111 stimulait le processus de cicatrisation tendineuse en augmentant la résistance du tendon et les contraintes nécessaires pour rompre celui-ci. D’autres expérimentations avec différentes concentrations de VEGF-111 sont actuellement en cours. [less ▲]

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See detailInfluence of the contraction mode on the tendon structure - Rat model
Kaux, Jean-François ULg; Drion, Pierre ULg; Besançon, Benoît et al

in 2nd Congress of European College of Sport & Exercise Physicians - Conference Brochure 2010: Abstracts and CVs (2010, September 09)

Introduction: Tendinopathies are common in sport and affect both upper and lower limbs. Eccentric rehabilitation is a successful way of treating them and now is becoming the “gold treatment”. Although ... [more ▼]

Introduction: Tendinopathies are common in sport and affect both upper and lower limbs. Eccentric rehabilitation is a successful way of treating them and now is becoming the “gold treatment”. Although clinical results are very favorable, beneficial morphological and histological effects have not yet been elucidated. The aim of our experiment was to determine if there exist any intrinsic modifications in a tendon trained in concentric or eccentric modes, in a rat model. Methods: 18 rats were divided into 3 groups: 6 for the control group, without physical restraint; 12 for a training of1 hour, 3 times a week, for 5 weeks, at a speed of 17m/min (1km/h), on a inclined treadmill: 6 rats running uphill at +15° for the concentric effort (group C) and 6 rats running downhill at -15° for the eccentric effort (group E). After this training period, the Achilles, patellar and tricipital tendons of both limbs were surgically removed in all 18 rats. Tendons taken from five rats of each group were subjected to a tensile test up to rupture using a “cryo” jaw. Tendons of the remaining rat of each group were subjected to a histological study. Results: The results showed significant changes in group E only: (1) an increase of the force required to rupture the patellar and tricipital tendons; (2) an improvement of the ratio between the force necessary to rupture the tricipital tendon and the body mass of the rats; (3) an increase of the surface area of the section of the tricipital tendon. No significant change was observed as far as constraint was concerned between groups. Histologically, we saw, in the group E, more peripheral blood vessels and a greater proportion of collagen. Conclusion: This study showed that the mechanical properties of tendon tissue are enhanced by eccentric training. Tendons become stronger, the amount of collagen increases and there is probably more interaction between collagen fibers (mechanotransduction). [less ▲]

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See detailVEGF-111 as a new therapeutic tool for tendon lesion
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent ULg et al

in Osteoarthritis and Cartilage (2010, September), 18(Supplement 2), 22

Introduction: Tendon lesion is one of the most frequent pathology in sports and by physical workers. This pathology often becomes chronic. For this reason, it is of interest to develop new treatments ... [more ▼]

Introduction: Tendon lesion is one of the most frequent pathology in sports and by physical workers. This pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Injection of platelet-rich plasma (PRP) seems to be a promising one by releasing growth factors (GF) locally. Among all the GF released by activated platelets, the vascular endothelial growth factor-A (VEGF-A) is known to induce positive effects on vascular function and angiogenesis, and could be implicated in the healing process of tendons. Recently, a novel VEGF-A isoform was identified, the VEGF-111, a biologically active and proteolysis-resistant VEGF-A isoform, also known to present beneficial effects on ischemic diseases. This prompted us to evaluate whether VEFF-111 would have a therapeutic interest within the framework of the tendon pathology. Methods: 60 Rats were divided into 2 groups: A: control (no injection), B: VEGF-111 treatment. A 5mm defect was surgically induced in rat Achilles tendon after resection of plantaris tendon. Rats received a local injection of VEGF-111 (100ng) in situ after the surgery and were placed in their cages without immobilization. After 5, 15 and 30 days, the traumatized Achilles tendons of 10 rats of both groups were removed and dissected during their healing process. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. Rats were then euthanized. Statistical analyses were made with an ANOVA. Values are significant when p-value is below 0.05. Results: Our results shown that the developed force necessary to induce tendon rupture during biomechanical tensile test was greater for tendons which had received an injection of 100ng of VEGF-111. These results were already noticed from day 5 onwards. The ratio between force and weight increased with time in both groups, but this ratio was greater for tendons which had been submitted to an injection of VEGF111. The surface area of the section of the tendons increased between 5 and 15 days followed by a stabilization. After 30 days, sections in both groups were similar. Thus, the constraint was similar after 5 and 15 days but was better for VEGF111 group after one month. Discussion - Conclusion: This experimentation has shown that a 100ng injection of VEGF-111 stimulated tendon healing process as suggested by the increased force needed to break tendons during its healing process and the increased of constraint in comparison with the control group. Other experimentations with different concentration of VEGF111 are now in process. Acknowledgement This experimentation was partially financed by “Standard de Liège 2007” and “Lejeune-Lechien 2008” grants. [less ▲]

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See detailPlatelet-Rich Plasma injection to improve tendon healing process
Kaux, Jean-François ULg; Drion, Pierre ULg; Renouf, Julien et al

in Osteoarthritis and Cartilage (2010, September), 18(Supplement 2), 221

Introduction It is well known that injured tendons do not heal easily. For example, tendinopathy is a condition which often becomes chronic in the case of bad or late management. Recently, several studies ... [more ▼]

Introduction It is well known that injured tendons do not heal easily. For example, tendinopathy is a condition which often becomes chronic in the case of bad or late management. Recently, several studies, essentially in vitro and, more recently, a few in clinical practice, have demonstrated the positive effects of platelets on the healing process of different tissues. In fact, platelets contain lots of growth factors which can be released after a local injection. These growth factors have the potentiality to enhance the tendon healing process, for example after rupture or tendinopathy. The aim of our experiment was to ascertain whether the use of Platelet-Rich Plasma (PRP) was of interest for accelerating the healing process of Achilles tendon after surgical induced lesion. Methods All experimental procedures and protocols used in this investigation / were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Liège. 60 rats were divided into 2 groups: A: control (no injection) and B: PRP injection. A 5mm defect was surgically induced in the rats’ Achilles tendon after resection of plantaris tendon. Rats of group B received a PRP injection in situ after the surgery. Afterwards, rats of both groups were placed in their cages without immobilization. After 5, 15 and 30 days, the traumatized Achilles tendons of 10 rats of both groups were removed and dissected during their healing process. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. Rats were then euthanized. Statistical analyses were made with an ANOVA. Values are significant when p-value is below 0.05. Results We observed that the force necessary to induce tendon rupture during biomechanical tensile testing increased with time in both groups; that this force was greater for tendons which had been submitted to an injection of PRP. The ratio between force and weight increased with time in both groups; that this ratio was greater for tendons which had been submitted to an injection of PRP too. There is also a significant interaction between time and the group. The surface area of the section of the tendons increased between 5 and 15 days followed by a stabilization. After 30 days, sections in both groups were similar. Thus, the constraint was similar after 5 and 15 days but is significantly better for PRP group after one month. Discussion – Conclusion We demonstrated that the force necessary to induce tendon rupture during biomechanical tensile testing was greater for tendons which had been submitted to an injection of PRP. These results were observed and significant (p<0.05) from day 5 onwards. We observed too that the section of the tendon was the same in both groups after 30 days. Thus the quality of the healing tendon is better with an injection of PRP, as shown with the increase of the constraint until rupture. Acknowledgement This experimentation was partially financed by “Standard de Liège 2007” and “Lejeune-Lechien 2008” grants. [less ▲]

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See detailUse of clinical biology techniques in clinical practice: injections of platelet-rich plasma to heal tendon
Kaux, Jean-François ULg; Le Goff, Caroline ULg; Drion, Pierre ULg et al

in Clinical Chemistry (2010, July), 56(S6), 111

Introduction: A tendon is a tissue which does not heal easily. For example, tendinopathy is a condition which often becomes chronic in the case of bad or overdue management. Several studies, essentially ... [more ▼]

Introduction: A tendon is a tissue which does not heal easily. For example, tendinopathy is a condition which often becomes chronic in the case of bad or overdue management. Several studies, essentially in vitro and, more recently, a few in clinical practice, have demonstrated the positive effects of platelets on the healing process of tendons. A local injection of platelet–rich plasma (PRP), which releases many growth factors, has the potentiality to enhance the tendon healing process. The aim of our experiment was to ascertain whether the use of PRP could accelerate the healing process of an Achilles tendon after a surgically induced lesion. Methods (*): PRP was obtained from the blood of 12 Sprague Dawley rats by cardiac puncture under general anaesthesia until the heart stopped beating. Quantities of 1mL of anticoagulant, adenosine-citrate-dextrose-acid (ACD-A), were added immediately to each 4,5mL of blood. The blood was then centrifuged at 180g for 10 minutes. To improve platelet concentration of the PRP, the supernatant was centrifuged for a second time at 1000g for 10 minutes. The platelets were then collected using a gauge pipette. Cell and platelet counts were made by an auto-analyser. Platelet concentration was around 2.2 to 2.9 x106/mm³. A 5mm defect was surgically induced in the Achilles tendon of 60 rats. Rats were divided into 2 groups of 30: A: a control group (no injection) and B: with a PRP injection. The rats of group B received a PRP injection in situ 1 hour after the surgery on the site of the lesion of the Achilles tendon. Fifty micro-litres of PRP were injected in each rat of the PRP group. Platelets were activated by the local presence of collagen in the wound. Afterwards, the rats of both groups were placed in their cages without immobilization. After 5, 15 and 30 days, 10 rats of each group were euthanized. The traumatized Achilles tendon of each rat was dissected and removed. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a tensile machine with a “Cryo-jaw”. Results: We demonstrated that the force necessary to induce tendon rupture during biomechanical tensile testing was greater for tendons which had been submitted to an injection of PRP. These results were observed and significant (p<0.05) from day 5 onwards. Discussion: This experimentation showed that PRP injections could accelerate the tendon healing process and increase the force needed to break tendons in their healing process. This “accelerating” process can be observed and is significant (p<0.05) as early as day 5. Conclusion: PRP, by the local release of growth factors, would be a new therapeutic tool to accelerate tendon healing. Acknowledgement: This experimentation was partially financed by “Standard de Liège” and “Lejeune-Lechien” grants. (*) All experimental procedures and protocols used in this investigation were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Liège. [less ▲]

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See detailNew use of VEGF in therapeutics: application in tendon lesions
Kaux, Jean-François ULg; Le Goff, Caroline ULg; Drion, Pierre ULg et al

in Clinical Chemistry (2010, July), 56(S6), 111

Introduction: As demonstrated in previous studies, mechanical overload, injury and inflammation, hypoxic condition or any combination of the above could lead to increased expression of VEGF in the tendon ... [more ▼]

Introduction: As demonstrated in previous studies, mechanical overload, injury and inflammation, hypoxic condition or any combination of the above could lead to increased expression of VEGF in the tendon. Thus, VEGF could participate in the healing of pathological tendons. Indeed, some authors are convinced that this neovascularization is the sign of a chronic tendinopathy while others plead in favour of it being a sign of healing processes. The VEGF111, which is a biologically active and proteolysis-resistant VEGF-A isoform, was recently identified. It is induced by ultraviolet B and genotoxic drugs. Experimentation shows that, in nude mice, tumors formed by HEK293 cells expressing VEGF111 develop a more widespread peritumoral neovascularisation than those expressing other VEGF isoforms. Good angiogenic activity and resistance to proteolysis makes VEGF111 a potential beneficial therapeutic option for ischemic diseases. The aim of our study was to determine whether if VEGF111 could have a therapeutic interest in the framework of tendinous pathology. Methods (*): A 5mm defect was surgically induced in Achilles tendon of 60 rats. Rats were divided into 2 groups of 30: A: a control group (no injection) and B: with a VEGF111 injection. The rats of group B received an injection of 100 ng of VEGF111 in situ 1 hour after surgery on the site of the tendon lesion. Afterwards, rats of both groups were placed in their cages without immobilization. After 5, 15 and 30 days, 10 rats of each group were euthanized. The traumatized Achilles tendon of each rat was dissected and removed. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a tensile machine with “Cryo-jaw”. Statistical analyses were made with an ANOVA. Results: A significant increase over time of the force necessary to induce tendon rupture was observed for tendons which had been submitted to an injection of VEGF111 (p=0.016). The force required to break the tendon is always greater for the VEGF111 group (p<0.05). Discussion: We demonstrated that the force necessary to induce the rupture of a rat’s Achilles tendon during biomechanical tensile testing was greater for tendons which had been submitted to an injection of VEGF111. Thus, this experimentation showed that VEGF111 injections could accelerate the tendon healing process and increase the force needed to break tendons in their healing process. Conclusion: VEGF111 could be a new therapy for tendon lesions. However, other experimentation using a rat model with different concentrations of VEGF111 should be made to ascertain the best concentration for this healing process. Acknowledgement: This experimentation was partially financed by “Standard de Liège” and “Lejeune-Lechien” grants. (*) All experimental procedures and protocols used in this investigation were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Liège. [less ▲]

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See detailComparison between platelet-rich plasma (PRP) and vascular endothelial growth factor-111 (VEGF-111) as a therapeutic tool in tendon healing process
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent ULg et al

Poster (2010, March 20)

Introduction In spite of the availability of various treatments for tendinopathy, this pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Among them, the ... [more ▼]

Introduction In spite of the availability of various treatments for tendinopathy, this pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Among them, the injection of platelet-rich plasma (PRP) seems to be a promising one. Indeed, several animal models have demonstrated that injection of blood platelets can initiate and stimulate tendon and ligament repair by releasing growth factors (GF) locally. Among all the GF released by activated platelets, the vascular endothelial growth factor-A (VEGF-A) is known to induce positive effects on vascular function and angiogenesis, and could be implicated in the healing process of tendons. Recently, a novel VEGF-A isoform was identified, the VEGF-111, a biologically active and proteolysis-resistant VEGF-A isoform, also known to present beneficial effects on ischemic diseases. This prompted us to evaluate whether VEFF-111 would have a therapeutic interest within the framework of the tendon pathology. Aim of the study: We hypothesized that the healing of ruptured Achilles tendons, which is the last stage of the Blazina’s classification, could be improved by injection of VEGF-111 that was compared to the potential effect of PRP injections using a rat model. Methods: A 5mm defect was surgically induced in rat Achilles tendon after resection of plantaris tendon. Rats were divided into 3 groups: A: control (no injection), B: PRP treatment and C: VEGF-111 treatment. Rats received a local injection of PRP (50µL) or VEGF-111 (100ng) in situ after the surgery and were placed in their cage without immobilization. After 5, 15 and 30 days, the rats were euthanized in each group. The traumatized Achilles tendon of each rat was removed and dissected during the healing process. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. Results: Our results show that developed force necessary to induce tendon rupture during biomechanical tensile test was more important for tendons which had received an injection of PRP or VEGF-111. Moreover, the tensile force necessary to break tendons is higher with PRP than with VEGF-111. These results were already noticed from day 5 onwards. Conclusion: This experimentation has shown that both PRP and VEGF-111 injections stimulated tendon healing process as suggested by the increased force needed to break tendons during its healing process. Furthermore, this acceleration of the cicatrisation process was more significant with PRP than with VEGF-111. This could be explained by the release from platelets of a “cocktail” of growth factors acting in synergy on the healing process. Acknowledgement This experimentation was partially financed by “Standard de Liège 2007” and “Lejeune-Lechien 2008” grants. [less ▲]

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See detailPlatelet-rich plasma (PRP) increases healing process of rats' Achilles tendons
Kaux, Jean-François ULg; Drion, Pierre ULg; Pascon, Frédéric ULg et al

Conference (2010, March 20)

Introduction Some tendinopathies (epicondylitis, jumper’s knee or Achilles tendinopathy) are frequently considered as rebel to “classic” treatments such as rest, orthotics, NSAIs, electrotherapy ... [more ▼]

Introduction Some tendinopathies (epicondylitis, jumper’s knee or Achilles tendinopathy) are frequently considered as rebel to “classic” treatments such as rest, orthotics, NSAIs, electrotherapy, physiotherapy, corticosteroid infiltrations, extracorporeal shock waves… Recently, several studies, essentially in vitro, demonstrated the positive effects of platelets on the healing process of different tissues: bones, muscles and tendons. Objectives The aim of our experiment was to ascertain whether the use of platelet-rich plasma (PRP) was of interest for accelerating the healing process of Achilles tendon after surgical induced lesion. Methods A 5mm defect was surgically induced in rat Achilles tendon after resection of plantaris tendon. Rats were divided into 2 groups: A: control (no injection) and B: PRP injection. Rats of group B received a PRP injection in situ after the surgery. Afterwards, rats of both groups were placed in their cage without immobilization. After 5, 15 and 30 days, rats were euthanized. The traumatized Achilles tendon of each rat was removed and dissected during this healing process. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. Results We demonstrated that the force necessary to induce tendon rupture during biomechanical tensile test study was more important for tendons which had been submitted to an injection of PRP. These results were noticed from day 5 onwards. Discussion – Conclusion This experimentation has shown that PRP injections could accelerate tendons healing process and increase the force needed to break tendons in their healing process. This “accelerating” process can be observed as early as day 5. Acknowledgement This experimentation was partially financed by “Standard de Liège 2007” and “Lejeune-Lechien 2008” grants. [less ▲]

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See detailLe PRP (Platelet-Rich Plasma) peut-il favoriser la régénération tendineuse ?
Kaux, Jean-François ULg; Drion, Pierre ULg; Pascon, Frédéric ULg et al

in Annales de Réadaptation et de Médecine Physique (2009, October), 52(Sup. 1), 109-110

Introduction : Certaines tendinopathies (l’épicondylite, la tendinopathie rotulienne supérieure ou encore la tendinopathie d’Achille) demeurent rebelles malgré un traitement « classique » bien conduit ... [more ▼]

Introduction : Certaines tendinopathies (l’épicondylite, la tendinopathie rotulienne supérieure ou encore la tendinopathie d’Achille) demeurent rebelles malgré un traitement « classique » bien conduit : repos, orthèse, AINS, électrothérapie, kinésithérapie, infiltrations de corticoïdes, ondes de choc... Certains travaux, essentiellement in vitro, soulignent les potentialités réparatrices des plaquettes qui présentent la capacité d’accélérer la cicatrisation de différents tissus : os, muscles et tendons. Objectifs : Le but de notre étude préliminaire est d’objectiver l’effet « accélérateur » sur la réparation tendineuse suite à l’emploi d’injection de plasma enrichi en plaquettes (platelet-rich plasma ou PRP) car cette technique pourrait représenter une thérapeutique d’avenir en médecine physique et en traumatologie du sport. Méthodes : Nous avons sectionné et réalisé un défect de 5mm dans le tendon d’Achille de rats (N = 12). Quatre rats ont bénéficié d’une injection in loco de PRP et remis en liberté comme les autres dans leur cage. Trois rats (2 sans PRP et 1 avec PRP) sont euthanasiés à J5, J10, J20 et J30 et le tendon d’Achille en cours de régénération est disséqué et prélevé. Une étude biomécanique de traction jusqu’à rupture est réalisé à l’aide de « Cryo-jaw ». Résultats : L’analyse des résultats montre que la force développée pour obtenir la rupture tendineuse doit être plus importante pour les tendons ayant bénéficié d’une injection de PRP et ce dès J5. Discussion – Conclusion : Cette série préliminaire permet de montrer que les injections de PRP permettent une accélération de la cicatrisation tendineuse et une augmentation des valeurs de résistances à la traction. Une étude avec un plus grand nombre de sujets est en cours. [less ▲]

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