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Tendon injury prevalence in both athletic and occupational settings is on the increase. Tendon healing properties are poor, despite the complex biological process triggered by the injury, which makes those injuries incapacitating for months. A significant proportion of these injuries remain difficult to treat, and many patients suffer from decreased performance and longstanding sequelae. While mechanical stabilization has been a hallmark of tendon surgical management, orthobiologics are playing an increasing role in optimizing tendon healing. Platelet rich Plasma (PRP), which is a volume of autologous plasma having platelet concentration above baseline, has been suggested as an accelerant orthobiological agent rich in supraphysiological concentration of growth factors. However, strong evidence of its mode of action and of its clinical efficacy is lacking. The purpose of this thesis is to identify the role of PRP in tendon regeneration in in-vitro and clinical studies. Firstly, the viability and biological components of clinically-prepared PRP were studied in novel experiments. This PRP was used in linked in-vitro studies to investigate the possible mechanism of PRP effect on the injured Achilles tendon cells and tissues. Cell count, viability, proliferation and DNA content were studied. The clinical application of PRP in Achilles tendon rupture was assessed in a randomised clinical pilot study using a combination of PROMs, objective outcome measures and a novel imaging modality called functional ultrasound elastography. This non-invasive technique was developed in a healthy-tendons volunteer study and its feasibility in ruptured tendons was assessed in the pilot trial. In another unique study, the immunohistochemical response to PRP was assessed in biopsies taken under US guidance at week 6 and compared to control to explore the possible mechanism of PRP effects. The findings confirmed that PRP is a viable activatable autologous blood product rich in growth factors. The results also confirmed that leukocytes and platelets are present in very high concentration with reversal of lymphocyte neutrophil ratio. Elastography volunteer study confirmed that FUSE is feasible using clinically applicable ultrasound scan. The improved algorithm allowed visualisation of localised strain within the studied tissues. The clinical application of PRP in Achilles tendon rupture revealed positive efficacy signal that PRP led to faster healing, improved pain and earlier restoration of function. However, the findings of this pilot trial were indicative and not confirmative. Immunohistochemistry analysis showed that PRP enhanced the maturity of the healing tendon tissues by promoting better collagen I deposition, improved Collagen III/Collagen I ratio, reduced cellularity, better vascular structure and higher GAGs content when compared with control. The finding may explain the clinical improvement observed in these patients at week 6 onwards. Linked in-vitro studies showed that autologous PRP with its cellular components, which include platelets, leukocytes and erythrocytes, has the ability to stimulate tendon cell migration to the injury site and stimulate proliferation in the injured human tendon. Additionally, it may maintain tissue viability in the hypoxic environment that follows tendon injury. Promoting migration and proliferation of cells and maintain tissue viability may play an important role to accelerate tendon healing. The findings of this project has informed the design of a phase II large multi-centre randomised controlled trial and helped secure major funding from the National Institute of Health Research (NIHR). This trial will set the scene for PRP use in tendon treatment.

L’ingénierie tissulaire vise à l’élaboration de prothèses biologiques par la régénération ou la culture, in vitro ou in vivo, de tissus ou d’organes. Dans la stratégie de culture in vitro, le développement de nouveaux outils, tels que des bioréacteurs, permettant la culture de cellules ou de tissus sous sollicitations mécaniques spécifiques au tissu est primordial. De plus, l’avancée de cette discipline dans la régénération des tissus nécessite de développer, dès à présent, des méthodes d’évaluation mécanique satisfaisantes permettant de comparer ces néo-tissus aux tissus sains selon des critères de sollicitations physiologiques. En effet, pour parvenir à une bonne évaluation de ces matériaux, il est nécessaire de pouvoir les tester sur des chargements représentatifs des sollicitations physiologiques auxquelles ils sont soumis. Nous avons ainsi, dans un premier temps, conçu et développé un bioréacteur de ligaments permettant la culture de cellules stimulées mécaniquement par des sollicitations cycliques de traction-torsion. Ce bioréacteur a été dimensionné afin de pouvoir obtenir des bio-prothèses de taille comparable aux ligaments et tendons à remplacer (4 à 5 cm de long). Nous avons, dans un deuxième temps, développé un modèle du comportement mécanique global de ces tissus à partir du formalisme thermodynamique développé au sein de notre laboratoire et des observations faites sur des tendons d’Achille de lapin. Ce modèle a pour but d’approfondir la compréhension des structures intervenant de façon prépondérante dans la qualité mécanique de ces tissus ainsi que l’évaluation et l’optimisation des matrices de support et des néo-tissus devant s’y substituer / Tissue Engineering aims to fabricate bio-prostheses by regenerating or culture, in vivo or in vitro, tissues or organs. In the in vitro strategy, developing new tools such as bioréactors which allow the culture of cells or tissues under their specific mechanical solicitations is a huge point. Moreover, the last advances of this discipline in regeneration of tissues require new mechanical model allowing their evaluation and comparison to native tissue under physiological loading. Indeed, in order to obtain a good evaluation of their mechanical quality, it is important to be able to applied mechanical solicitations linked to physiological ones. As a first step, a bioreactor of ligament allowing the culture of cells under mechanical solicitations of cyclic traction-torsion was designed and developed. This bioreactor was sized to potentially obtain a bio-prosthesis comparable to native tissue in term of size (4 to 5 cm long). In a second time, a mechanical model was elaborated based on a thermodynamic formalism developed in our laboratory and the observation made on rabbit Achilles tendons. The goals of this model are to improve our knowledge on the mayor structures involved into the mechanical quality of theses tissues and to evaluate and optimise the scaffolds and neo-tissues of substitution

Zur Zeit gibt es keinen optimalen Sehnentransfer zur Behandlung von irreparablen Ruptur der Subscapularissehne. Obwohl der Pectoralis major Transfer als Therapie der Wahl gilt, bleibt der Kraftvektor der verlagerten Sehne-Muskeleinheit sehr unterschiedlich zum Kraftvektor des Subscapularismuskels. Das Ziel dieser Arbeit war, ein neues Konzept zur Behandlung von irreparablen Subscapularisrupturen zu definieren, bei dem die Subscapulariseinheit selektiv mittels Teres major(TM) und Pectoralis major (PM) wiederhergestellt wird. In den Kadaverstudien dieser Arbeit konnte gezeigt werden, dass sich der M. Teres major anatomisch-chirurgisch als Sehnentransfer zur Rekonstruktion der unteren Hälfte des M. Subscapularis eignet. Darüberhinaus wurde in einer dreidimensionalen Vektoranalyse gezeigt, dass der Kraftvektoren vom verlagerten Teres major sich nicht signifikant vom Kraftvektoir des unteren Anteils des Musculus subscapularis unterscheidet. Es wurde weiterhin gezeigt, dass Modifikationen des Pectoralis major transfer durch Reroutingmassnahmen zu einer deutlichen Verbesserung seines Kraftvektors im Vergleich zum oberen Amteil des Musculussubscapularis führt. Basierend auf den neuen anatomischen und biomechanischen Erkenntnissen wurde im letzten Teil dieser Schrift das neue Konzept klinisch angewandt. Dabei wurde bei 7 Patienten mit einer irreparablen Subscapularisruptur nach multiplen Voreingriffen eine selektive Rekonstruktion mittels kombinierten TM-PM Transfer durchgeführt. Es traten keine Komplikationen auf und alle Patienten hatten eine deutliche Linderung Ihrer Schmerzen und eine Verbesserung der Funktion. Somit erscheint diese neue Transferoperation eine sichere und effiziente Option zur Behandlung irreparabler Subscapularisrupturen darzustellen. / Currently there is no optimal tendon transfer procedure for the management of irreparable subscapularis lesions. Although the pectoralis major transfer is considered as the gold standard in the treatment of irreparable subscapularis tears, the force vector orientation of this transfer may not be optimal in comparision to the situation at the subscapularis muscle. Objective of this monograph was to establish the anatomical and biomechanical basis for a new concept of selective subscapularis reconstruction combining a teres major transfer to the pectoralis major transfer. In the cadaveric part of this work, it could be demonstrated that the teres major is a safe and biomechanically logical transfer for reconstruction of the lower part of the subscapularis. The analysis was carried on to define the optimal transfer for reconstruction of the upper part of the subscapularis. It was possible to determine the biomechanical effect of rerouting procedures of the pectoralis major transfer. Passing the tendon underneath the conjoined tendon appeared to be the most effective way to improve the direction of the pectoralis major transfer for subscapularis reconstruction. However this technique is demanding when the plane underneath the conjoined tendon is scarred and the pectoralis major is bulky. In such cases there is a risk to injure the musculocutaneous nerve. Therefore, rerouting the sternal part of the pectoralis major underneath its clavicular part (sPM tansfer) may be a safer option. Finally, based on the acquired anatomical and biomechanical data, early clinical experience in a series of 7 patients was reported. Although the clinical series was small, the combined TM-sPM transfer appeared to be a valuable and a safe alternative to treat irreparable subscapularis tears. An interesting observation in this study was that the transfer was able to recenter the statically subluxed humeral head in two cases. This could be attributed to the dynamic hammock built by the transferred teres major. The early promising subjective and objective results presented here encourage for further investigation.

Matrix metalloproteinases (MMPs), such as collagenases, are a family of enzymes capable of degrading most constituents of the extracellular matrix. MMPs are thought to be involved in the aetiopathogenesis of tendon rupture. Additionally, failure of healing has in some instances been associated with elevated levels of MMPs. We have studied (a) the effects of the MMP-inhibitor doxycycline on healing of tendons and intestines in experimental models and (b) systemic levels of MMPs and their endogenous inhibitors (TIMPs) in patients with tendon rupture. In the first study, systemic doxycycline treatment lead to weakened rat Achilles tendons during healing after injury. Subsequently, systemic doxycycline was shown to improve biomechanical properties of tendon suture fixation in the rat Achilles tendon. Sutures were also coated with doxycycline, leading to similar improvement in mechanical strength of the suture construct during healing. In the third study, doxycycline-coated sutures improved the strength of healing intestinal anastomoses in an experimental model. Finally, we showed that patients with a history of Achilles tendon rupture had elevated levels of MMP-2, MMP-7 and TIMP-2 in serum. In addition, MMP-7 correlated inversely to mechanical strength of the tendon during healing. In conclusion, MMP-inhibitors can be administered systemically and locally to manipulate healing of tendons and intestines. Generalised alterations in the MMP-TIMP system may be involved in the pathogenesis of Achilles tendon rupture and associated with differences in outcome of healing.

[pt] Este trabalho apresenta um estudo experimental sobre a redistribuição de momentos em vigas contínuas de concreto construídas em aduelas pré-moldadas, com juntas secas, e protendidas com cabos sintéticos externos. Para tanto foram ensaiadas quatro vigas contínuas, com dois vãos iguais, sendo uma monolítica e as demais em aduelas pré-moldadas. Todas as vigas têm a mesma seção transversal tipo I, com dois vãos, altura da seção de 30 cm, largura do flange e espessura da alma igual a 30 cm e 10 cm, respectivamente. A viga monolítica tem relação 1/dp (vão/altura) igual a 18,75 e nas vigas em aduelas os valores desta relação foram entre 12,5, 18,75 e 25. As vigas são protendidas com dois cabos sintéticos externos com traçado poligonal. Os cabos utilizados são feitos com fibras sintéticas de alta resistências (2700 MPa) e alto modulo de elasticidade (126000 MPa) conhecidas comercialmente como Kevlar. O objetivo deste estudo é examinar a redistribuição de momentos em vigas contínuas com sistemas construtivos diferentes e com diferentes relações 1/dp frente à utilização de cabos sintéticos. Os resultados mostram que a redistribuição de momentos em vigas em aduelas pode ser obtida a partir de uma viga monolítica semelhante e que o comportamento da redistribuição de momentos nas vigas em aduelas é pouco influenciada pela relação l/dp. / [en] An experimental investigation on the behavior of continuous segmental concrete beams, prestressed with external aramid tendons, was carried out. Four beams were tested; one was monolithic and the others were constructed in precast dry- jointed segments. All the beams had the same overall dimensions, with two spans and an I section 30 cm high, flange width of 30 cm and web thickness of 10 cm. The 1/dp span/section height) ratio was 18,75 for the monolithic beam and 12.5, 18.75 and 25 for the segmental beams. The beams were post-tensioned with two external aramid tendons, which are made of high strength (2700 MPa) high modulus (126000 MPa)Kevlar 49 yarns. The main objective was to study the moment redistribution in the post-cracking stage. Test results have shown that the moment redistribution in segmental beams can be obtained from a similar monolithic beam and that the moment redistribution is only slightly affected by the 1/dp.

Made available in DSpace on 2016-06-02T20:19:19Z (GMT). No. of bitstreams: 1 DissACBS.pdf: 10545595 bytes, checksum: 079933a164ff065ae11e54e43ae5200a (MD5) Previous issue date: 2004-12-20 / The purpose of this study was to analyze the 660 nm GaAlAs laser effect with 10 mW and 40 mW, during 10 seconds, on angiogenesis process and repair quality after partial lesion of Achilles tendon in rats. It was used 104 male rats, that 96 rats had been submitted to lesion by a falling of 186 g from a height of 20 cm, above the right tendon. These rats had been randomly divided in 3 groups, treated in 3 (n = 32), 5 (n = 32) and 7 (n = 32) days, respectively. Each of these groups was divided again into 4 subgroups, which were submitted to laser with mean output of 10 mW (n = 8) and 40 mW (n = 8), a sham treatment (n = 8), and a group with no treatment (n = 8). The analyzes were made by vessels count that have been previous prepared with nanquim ink and by a semiqualitative analyze of polynuclear cells presence, mononuclear cells presence, collagen organization and neovascularization. A fourth group with 8 animals was established as control, without lesion and used as reference for qualitative analyze. The comparison of the groups made evident that the animals submitted to laser showed more vessels number than the control groups (p<0,05) and the 40 mW subgroup showed better vascularization than the others after 3 days of irradiation. (p<0,01). The semiqualitative analyze showed statistical difference (p<0,05) when considering collagen organization and neovascularization in the comparison between the 10 mW, 40 mW and control. Qualitatively, the groups treated with laser showed better repair aspect. The results permit us to conclude that Low Level Laser Therapy with 660 nm promoted an increase of the blood vessels number and better repair quality and the mean output of 40 mW had begun the neovascularization precocious, showing significant difference after 3 days of application. / A proposta desse estudo foi analisar os efeitos do laser AsGaAl, de 660 nm, com 10 mW e 40 mW de potência de saída, aplicado durante 10 segundos, no processo de angiogênese e qualidade de reparo após lesão parcial do tendão calcâneo de ratos. Foram utilizados 104 ratos machos, sendo que 96 foram submetidos à lesão com a queda de um peso de 186 gramas na altura de 20 cm sobre o tendão direito. Estes foram divididos aleatoriamente em 3 grupos, tratados em 3 (n = 32), 5 (n = 32) e 7 (n = 32) dias, respectivamente. Cada um desses grupos foi ainda dividido em 4 subgrupos, submetidos ao laser com potência de saída de 10 mW (n = 8) e 40 mW (n = 8), grupo placebo (n = 8) e grupo sem tratamento (n = 8). As análises foram feitas através da contagem dos vasos que foram previamente corados com tinta nanquim e por meio de uma análise semiqualitativa da presença de células polimorfonucleares, mononucleares, organização de colágeno e neovascularização. Um quarto grupo com 8 animais foi estabelecido como controle padrão, sem lesão que foi utilizado como referência para a análise qualitativa. A comparação dos grupos evidenciou que os animais irradiados mostraram maior número de vasos do que os grupos controle (p<0,05) e o subgrupo de 40 mW apresentou melhor vascularização que os demais após 3 dias de irradiação (p<0,01). A análise semiqualitativa evidenciou diferença estatística (p<0,05) quando foi considerada a organização de colágeno e a neovascularização na comparação entre os grupos 10 mW e 40 mW com os controle. Qualitativamente os grupos tratados com laser apresentaram melhor aspecto do reparo. Os resultados nos permitem concluir que a terapia laser de baixa intensidade, com comprimento de onda de 660 nm promoveu aumento na neovascularização e melhora na qualidade de reparo e a potência de saída de 40 mW iniciou a neovascularização precocemente, mostrando diferença significativa após 3 dias de aplicação.

Le complexe muscle-tendon est constitué d’une composante élastique série fondamentale à son fonctionnement. Cette composante élastique série est composée d’une fraction active située au sein du sarcomère et d’une fraction passive formée par les tissus tendineux (tendon et aponévrose). Elle a un rôle majeur pour optimiser le mouvement en améliorant le rendement énergétique du muscle et le travail produit.La mise au point d’une nouvelle méthode couplant une technique de détente rapide (Quick release) et un échographe haute fréquence a permis de quantifier les contributions de compliance des structures élastiques séries (tendon, aponévrose et fascicules musculaires) à la compliance globale du complexe muscle-tendon en condition active lors d’un test de détente rapide. Les résultats de la première étude montrent que le tendon a une contribution de compliance majoritaire (environ 72 %) tandis que les fascicules musculaires et l’aponévrose contribuent respectivement à 18 % et 10 %. Le tendon confirme donc son rôle capital dans la compliance de la composante élastique série en condition active. De plus, les contributions constantes du tendon, des fascicules musculaires et de l’aponévrose observées aux différents niveaux de couple pourraient aider à simplifier le mécanisme de régulation de la compliance et à maintenir le rôle majeur du tendon dans l’efficience du mouvement.Cette nouvelle méthode a permis d’étudier les adaptations mécaniques de la composante élastique série à la variation de la demande fonctionnelle, notamment en quantifiant les modifications des contributions relatives de compliance des structures élastiques séries chez des escrimeurs élites dans la deuxième étude puis chez des sujets spastiques dans la troisième étude. Concernant les escrimeurs élite, les résultats montrent que les contributions de compliance des structures élastiques de la jambe dominante du groupe d’escrimeurs sont significativement différentes à celles correspondant à la jambe du groupe contrôle, avec notamment une part plus importante de contribution pour l’aponévrose (21,1 vs 15,9 %) et une part minorée pour les fascicules (9,5 vs 13,8 %) concernant la jambe dominante des escrimeurs. En revanche, la contribution du tendon (environ 70 %) est identique pour les deux jambes. Ces modifications tendent à majorer le rôle des tissus tendineux (tendon et aponévrose) et à minorer le rôle des fascicules musculaires ce qui permettrait une utilisation supérieure des structures élastiques tendineuses pour un meilleur rendement énergétique et une performance accrue. Il est possible que l'aponévrose soit un système complémentaire à l’adaptation du complexe muscle-tendon en cas d'hyperactivité.La troisième étude est devenue une étude de cas en raison de la difficulté à tester les patients spastiques sur le Quick release. Elle s’est portée sur un patient spastique dont l’atteinte motrice était plus faible que les autres et a montré des contributions relatives de compliance du tendon (75,3 %) et de l’aponévrose (15,2 %) supérieures à celle des fascicules (9,5 %) Ce résultat s’expliquerait par une augmentation de la raideur du muscle et une diminution de la raideur des tissus tendineux observées classiquement dans les études menées sur des sujets spastiques. / The muscle-tendon complex contains a serie elastic component which is fundamental to its functioning. This serie elastic component is composed of an active part located within the sarcomere and a passive part located in the tendon and aponeurosis. It has a major role to optimize the movement by improving the muscle energetic efficiency and the produced work.A new method coupling a quick release ergometer and a high frequency ultrasound device was used to quantify the compliance contributions of the series elastic structures (tendon, aponeurosis and muscle fascicles) to the global compliance of the muscle-tendon complex in active conditions. The results of the first study showed that the tendon has a major compliance contribution (about 72%) while the muscle fascicles and aponeurosis contributions are 18% and 10%, respectively. The tendon confirms its key role in the compliance of the serie elastic component in active condition. In addition, the constant contributions of tendon, muscle fascicles and aponeurosis observed at various levels of torque may help simplify the regulation mechanism of compliance and maintain the major role of the tendon in the efficiency of the movement.This new method was also used to study the mechanical adaptations of the serie elastic component to variation of the functional demand. The changes in the relative compliance contributions of series elastic structures were quantified in elite fencers in the second study and in spastic subjects in the third study. Regarding the elite fencers, the results showed that the compliance contributions of the elastic structures in the dominant leg of fencers group were significantly different to those corresponding to the leg of the control group. The aponeurosis compliance contribution was higher for the dominant leg of the fencers groupe (21.1 vs 15.9%) while the muscle fascicles contribution was lower for the fencers group (9.5 vs 13.8%). The tendon contribution (about 70%) was the same for both legs. These changes tend to increase the role of tendon tissue (tendon and aponeurosis) and decrease the role of muscle fascicles which would allow greater use of tendon elastic structures for better energetic efficiency and improved performance. It is possible that aponeurosis is a complementary system to the adaptation of the muscle-tendon complex in the case of hyperactivity.The third study has become a case study because of the difficulty in testing the spastic patients on Quick release. Finally, the study has been done on a spastic patient with minor motor impairment compared to the others patients. The results showed a tendon and aponeurosis compliance contributions (75.3% and 15.2% respectively) higher than the muscle fascicles compliance contribution (9.5%). This result may be explained by an increase in muscle stiffness and a decrease in tendon stiffness, which is classically observed in studies with spastic subjects.

Le système musculo-squelettique se compose des muscles, du squelette et du tissu conjonctif qui comprend, entre autres, les tendons et le tissu conjonctif musculaire. Le tissu conjonctif musculaire contribue à l'élasticité et à la rigidité des muscles, alors que les tendons transmettent les forces musculaires à l'os nécessaires aux mouvements du corps. Contrairement au muscle et au squelette, la mise en place et la formation du tissu conjonctif restent à ce jour peu étudiées. Afin d'identifier les mécanismes moléculaires sous-jacents à la formation du tissu conjonctif au cours du développement du membre, cinq facteurs de transcription à doigt de zinc ont été examinés : OSR1, OSR2, EGR1, KLF2 et KLF4. Ces facteurs de transcription sont exprimés dans différents sous-compartiments du système musculo-squelettique et leur surexpression influence la différentiation des cellules mésenchymateuses du membre. Afin d'élucider leurs rôles au niveau de la régulation génique, plusieurs stratégies à haut-débit (RNA-seq, ChIP-seq) ont été mises en place. Ces stratégies ont permis : (i) d'identifier que les facteurs de transcription partagent des fonctions régulatrices communes liées à la transduction du signal, à la communication cellulaire et à l'adhésion cellulaire ; (ii) de révéler que les gènes différentiellement exprimés étaient enrichis pour des signatures d'activation et de répression chromatiniennes, suggérant qu'ils sont dynamiquement régulés ; (iii) de distinguer les gènes cibles directs des cibles indirectes. Ces résultats fournissent ainsi une base pour des travaux futurs visant à mieux comprendre l'inter-connectivité entre les différents composants de l'appareil locomoteur. / The musculoskeletal system is composed of muscles, skeletal elements and connective tissues such as tendon and muscle connective tissue. Muscle connective tissue contributes to the elasticity and rigidity of muscles, while tendons transmit forces generated by muscles to the bone to allow body motion. In contrast to muscle and skeleton, connective tissue patterning and formation remain poorly investigated. In order to identify molecular mechanisms underlying connective tissue formation during limb development, five zinc-finger transcription factors were investigated: OSR1, OSR2, EGR1, KLF2 and KLF4. These transcription factors are expressed in distinct subcompartments of the musculoskeletal system and influence the differentiation of limb mesenchymal cells upon overexpression. To further investigate their roles at the molecular level, several genome-wide strategies (RNA-seq, ChIP-seq) were employed. These strategies enabled: (i) to identify that the transcription factors share common regulatory functions and positively regulate biological processes related to signal transduction, cell communication and biological adhesion; (ii) to reveal that the differentially expressed genes were enriched for both active and repressive chromatin signatures at their promoters, suggesting that they are dynamically regulated; (iii) to distinguish between indirect and direct target genes. Altogether, these results provide a framework for future investigations to better understand the interconnectivity between components of the musculoskeletal system.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-06-18T21:18:10Z No. of bitstreams: 1 Anna Cristina de Farias Marques.pdf: 2073138 bytes, checksum: 63fce77ba3e8c96e01965f2b4cecc62c (MD5) / Made available in DSpace on 2018-06-18T21:18:10Z (GMT). No. of bitstreams: 1 Anna Cristina de Farias Marques.pdf: 2073138 bytes, checksum: 63fce77ba3e8c96e01965f2b4cecc62c (MD5) Previous issue date: 2015-12-18 / This study investigates the effect of low-level laser therapy (LLLT) on collagen type I and III, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF) in experimentally induced tendinopathy in female aged rats. Tendinopathy was induced by collagenase peritendinous of the Achilles tendon. Forty-two Wistar rats (Norvegicus albinus) were used; groups consisted of 36 aged animals (18 months old; mean body weight, 517.7 ± 27.54 g) and 6 adult animals (12 weeks old; mean body weight, 266 ± 19.30 g). The animals were randomlydivided in three groups: control, aged tendinopathy, and aged tendinopathy LLLT; the aged groups were subdivided according to experimental periods: 7, 14, and 21 days. LLLT involved a gallium-arsenide-aluminum laser (Theralaser, DMC®) with active medium operating at wavelength 830 ± 10 nm, 50 mW power, 0.028 cm2 laser beam, 107 J/cm2 energy density, 1.7 w/cm2 power density, and 6 J of energy, with a frequency of 3 times per week, until euthanasia. VEGF, MMP-3, and MMP-9 were analyzed by immunohistochemistry, and collagen type I and III by Sirius red. LLLT increased the deposition of collagen type I and III in a gradual manner, with significant differences relative to the group aged tendonitis (p<0.001), and in relation to VEGF (p<0.001); decreased expression of MMP-3 and 9 was observed in group aged tendinopathy (p<0.001). LLLT, therefore, increased the production of collagen type I and III, downregulated the expression of MMP-3 and MMP-9, and upregulated that of VEGF, with age and age-induced hormonal deficiency. / O objetivo deste estudo foi investigar O Efeito da terapia Laser de baixa intensidade no Colágeno tipo I e III, Metaloproteinase e VEGF em Modelo Experimental de Tendinopatia, em ratas fêmeas idosas. A colagenase foi induzida na região peritendínea no tendão Calcâneo dos animais. Quarenta e duas ratas Wistar (Norvegicus albinus) foram utilizadas no estudo, com grupos consistindo de 36 animais idosos (18 meses de idade; com média da massa, 517.7 ± 27.54 g) e 6 animais adultos (12 semanas de idade; média da massa, 266, 19:30 0 ± g). Os animais foram randomizados e divididos em três grupos, Controle, tendinopatia idoso e tendinopatia Laser idoso, e subdividido em três grupos experimentai, 7, 14 e 21 dias. O tratamento com Laser de baixa intensidade foi aplicado utilizando um Laser Arseneto de Galium e Alumínio (AsGaAl) (Theralaser, DMC®) operando no comprimento de onda de 830nm (±10nm), 50 mW de potência, saída do feixe de 0,028 cm2, densidade de energia de 107J /cm2, densidade de potência 1,7 w/cm2 e energia de 3 J, com uma frequência de 3 vezes por semana, até a data da eutanásia (7, 14 e 21 dias). Foram analisados VEGF e MMP 3 e 9 por meio de Imunohistoquímica e Colágeno tipo I e III por Sirius red. Os resultados sugerem que a Terapia a Lesar de Baixa Intensidade foi capaz de aumentar os níveis de Colágeno tipo I e III de maneira gradual e com significante diferença no grupo Tendinpatia Idoso (p<0,001), isso pode ser observado em relação ao VEGF (p<0.001), foi também observado diminuição da expressão de MMP 3 e MMP 9 em relação ao grupo tendinopatia Idoso, com diferença estatística (p<0,001). Nós concluímos que a terapia Laser de Baixa Intensidade foi capaz de diminuir a produção de Colágeno tipo I e III, reduzir a expressão de MMP 3 e 9, e aumentar a expressão de VEGF, mesmo nas ratas fêmeas idosas com deficiência hormonal causada pela idade.