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1
Blomgran, Parmis. "Inflammation and tendon healing." Doctoral thesis, Linköpings universitet, Avdelningen för Kirurgi, Ortopedi och Onkologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-142349.
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Tendons heal through three different overlapping phases; the inflammatory, proliferative and remodeling phase. Many studies have investigated what factors influence healing of tendons. However, little was known about inflammation and the immune cells present during Achilles tendon healing by the time this thesis started. We developed a flow cytometry method for our rat model of tendon healing, which enabled us to study different leukocyte subpopulations during Achilles tendon healing. The general aim of this thesis was to understand more about inflammation and the immune cell populations present during tendon healing and how the immune cell composition changes during normal tendon healing. Moreover, we investigated how different factors that are known to influence tendon healing affected the composition of the immune cell population. First, we described the immune cells during the time course of tendon healing focusing on different subpopulations of macrophages and T cells. Then, we studied how these cells were influenced by reduced mechanical loading. Mechanical loading prolonged the presence of M1 macrophages and delayed the switch to regulatory T cells and M2 macrophages compared to reduced mechanical loading. Next, the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the leukocyte composition revealed that, even though NSAIDs influence the mechanical properties of healing tendon, this effect was not mediated via changes in the leukocyte sub-populations during early and mid-time tendon healing. Further, the effect of corticosteroids during the inflammatory and remodeling phases of tendon healing was an improved healing of tendons and a reduction of CD8a T cells when corticosteroid was administered after the inflammatory phase. Lastly, we investigated if impairment of tendon healing by NSAIDs was related to mechanotransduction or microdamage during mechanical loading and showed that NSAIDs impair tendon healing by reducing the response to microdamage. In conclusion, these studies show that inflammation plays an important role during Achilles tendon healing, and factors that influence healing can also alter the presence or polarization of immune cell populations.
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Murrell, George Anthony Calvert St George Clinical School UNSW. "Nitric oxide and tendon healing." Awarded by:University of New South Wales. St George Clinical School, 2006. http://handle.unsw.edu.au/1959.4/31887.
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Nitric oxide is a small free radical generated by family of enzymes, the nitric oxide synthases. In a series of experiments performed over the last 15 years we showed that nitric oxide is induced by all three isoforms of nitric oxide synthase during tendon healing and that it plays a crucial beneficial role in restoring tendon function. In normal tendon we found very little nitric oxide synthase activity while in injured rat and human tendons nitric oxide synthase activity was expressed in healing fibroblasts in a temporal fashion. In healing rat Achilles tendon fibroblasts the first isoform to be expressed was endothelial nitric oxide synthase (eNOS), followed by inducible nitric oxide synthase (iNOS), and then brain or neuronal nitric oxide synthase (bNOS). Systemic inhibition of nitric oxide synthase activity decreased the cross sectional area and mechanical properties of the healing rodent Achilles tendons. Addition of nitric oxide via NO-flurbiprofen or NO-paracetamol enhanced rat Achilles tendon healing. Addition of nitric oxide to cultured human tendon cells via chemical means and via adenoviral transfection enhanced collagen synthesis, suggesting that one mechanism for the beneficial of nitric oxide on tendon healing might be via matrix synthesis. The final part of the work involved three randomized, double-blind clinical trials which evaluated the efficacy of nitric oxide donation via a patch in the management of the tendinopathy. In all three clinical trials there was a significant positive beneficial effect of nitric oxide donation to the clinical symptoms and function of patients with Achilles tendinopathy, tennis elbow and Achilles tendonitis.
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Molloy, Timothy John St George Clinical School UNSW. "Gene expression in healing tendon." Awarded by:University of New South Wales. St George Clinical School, 2006. http://handle.unsw.edu.au/1959.4/23939.
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Tendon injury is painful and often debilitating, and is a one of the most prevalent soft tissue injuries encountered in the clinic. While common, the underlying molecular and genetic processes of tendon damage and repair remain poorly understood. The work described herein used genome-wide expression analyses to investigate tendon injury and healing from three perspectives. The first identified novel gene expression in tendon fibroblasts following their stimulation with nitric oxide (NO). Of particular relevance to tendon healing was the observation that stimulated fibroblasts express a number of extracellular matrix (ECM) genes in response to NO in a dose-dependent manner, and that NO significantly affects cellular adhesion, a critical process during tendon repair. These findings will be of use when optimising dosages of NO delivery in future work investigating NO as potential treatment for tendon injuries. The second study examined gene expression in an acute tendon injury model in the rat at 1, 7, and 21 days post injury, roughly representing the inflammation, proliferation, and remodelling phase of wound repair. Several novel genes and pathways were found to be differentially expressed at each stage of healing. Of particular interest were the presence of a significant number of genes related to glutamate signaling, a method of cellular communication that has not previously been shown to exist in tendon. Also upregulated were a number of genes which have previously only been associated with embryonic development. Finally, gene expression in a supraspinatus tendinopathy model in the rat was investigated. Several genetic pathways were identified in tendinopathic tendons which have not previously been associated with the disease, and, analogous to the acute injury model study, glutamate signaling gene overexpression was also prevalent. Further in vitro studies showed that the expression of these genes in tendon fibroblasts were stimulated by glutamate treatment, which in turn upregulated pro-apoptotic pathways causing cell death. This may prove to be an important causative factor in the tendon degeneration seen in tendinopathy, in which apoptosis has been identified as playing a significant role. The results of these studies contribute to a better understanding of the aetiology of several extremely common pathologies of this soft tissue, and may help to develop more targeted therapies for increasing the efficacy of tendon healing in future.
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Berglund, Maria. "Biomolecular Aspects of Flexor Tendon Healing." Doctoral thesis, Uppsala universitet, Handkirurgi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-120304.
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Flexor tendon injuries in zone II of the hand (i.e. between the distal volar crease and the distal interphalangeal joint) can be costly for both the afflicted individual and society because of the high cost of a long rehabilitation period, complicated by tendon ruptures or scarring with adhesion formation, causing impaired range of motion. The aim of the present thesis was to characterize more fully the deep flexor tendon, the tendon sheath and their response to injury in a rabbit model in order to find potential targets to improve the outcome of repair. The intrasynovial rabbit deep flexor tendon differed from the extrasynovial peroneus tendon in the expression of collagens and transforming growth factor-β1 gene expression. Differences were also found in collagen III and proteoglycans between regions of the flexor tendon subjected to either compressive or tensile load. After laceration and subsequent repair of the flexor tendon, a shift in collagen gene expression from type I to type III occurred. Proteoglycans were generally increased with the notable exception of decorin, a potential inhibitor of the profibrotic transforming growth factor-β1 which was markedly increased during the first two weeks after repair in tendon tissue but remained unaltered in the sheaths. Both vascular endothelial growth factor and basic fibroblast growth factor mRNA levels remained essentially unaltered, whereas insulin-like growth factor-1 increased later in the healing process, suggesting potential beneficial effects of exogenous addition, increasing tendon strength through stimulating tenocyte proliferation and collagen synthesis. Matrix metalloproteinase-13 mRNA levels increased and remained high in both tendon and sheath, whereas there was only a transient increase of matrix metalloproteinase-3 mRNA in tendon. We could also demonstrate a significant increase of the proportion of myofibroblasts, mast cells and neuropeptide containing nerve fibers in the healing tendon tissue, all components of the profibrotic myofibroblast-mast cell-neuropeptide pathway.<br>Biomolecular aspects of flexor tendon healing
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Schepull, Thorsten. "Stiffness of the healing human Achilles tendon." Doctoral thesis, Linköpings universitet, Institutionen för klinisk och experimentell medicin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-91727.
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Achilles tendon ruptures in humans are followed by a long period of immobilisation, rehabilitation and limitations of physical activity and sometimes work also. This prolonged period probably leaves a marginal for improvement in the management of this injury. Animal studies have shown that there are several possibilities to influence and improve tendon healing. The aim of this thesis was to find a way to examine the mechanical properties of the healing human Achilles tendon and, by using that method, to gain a better understanding of the tissue properties and healing process in these tendons. It was also our aim to use our knowledge from animal studies in an attempt to improve tendon healing in humans. We developed a radiological method using radiostereophotogrammetric analysis (RSA) and computed tomography (CT), which enabled us to measure the stiffness of the healing Achilles tendon. The results of these measurements, as early as 7 weeks after injury correlated with the late clinical results in all studies. Clinical results were measured using a heel-raise test comparing the injured with the non-injured tendon. We could not find a significant difference in stiffness between patients treated surgically or non-surgically. Neither could we demonstrate that platelet-rich plasma improved the mechanical properties of the healing tendon or the clinical outcome, within the limits of the statistical power. In contrast, patients following a specific training programme with early tension loading of the tendon twice a day developed stiffer tendon tissue later in the healing process. Since RSA is unsuitable for routine clinical use, we evaluated the possibility to use radiodensity findings from CT as a proxy for healing and its correlation to mechanical and clinical results. Density and mechanical properties correlated strongly when analysing all time points together, but only weakly at each particular point in time. Density may still be useful in describing mechanical properties at a later stage of repair, but this remains to be seen. In conclusion, these studies show that early mechanical properties correlate to late clinical outcome and that the early use of daily tension loading sessions leads to an improvement in the mechanical properties of the tendon tissue.
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Brooks, Jonathan Peter. "The biology of the tendon in development and healing." Thesis, University of Manchester, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.488287.
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The biology of tendons has been extensively investigated previously. Many studies have looked into the development and healing of tendons. An overall picture of the events in tendon development and healing, in terms of recently recognised functional molecules is missing, particularly in a single model. The recent understanding of the importance of metalloproteinases and other enzymes in ECM degradation suggests they may be of importance in tendon healing and development. Another unexplored area with relevance to wound healing and development is the functional integrin molecules. This thesis looked at the spatial and temporal localisation of a wide range of functional molecules and at cell proliferation. The subject groups were tendon development, from the limb bud to juvenile animal, and a defined reproducible adult healing model, with time points to six months. The study was then extended to fetal tendon healing. The results were analysed qualitatively using immunohistology and the findings were supported by histological and ultrastructural analysis, which reproduced the findings of previous studies and allowed novel observations. Adult tendon healing was accessible to quantitative analysis, which added further weight to the results. Tendon wounds in the adult model were noted to be asymmetrical in terms of tissue fibrillation, and immunohistology on opposite sides of the wound. Observations of integrin and cytoskeletal patterning in the wound, suggested mechanical load may have modulated this effect. A further study looked at a defined set of wound models. These modified the mechanical load and tissue perfusion of the wound to reproduce the effects in symmetrical wounds. The results showed that the spatial and temporal localisation of collagens, growth factors, enzymes and integrins and cell proliferation were modulated over a six month healing period. This was supported by quantitative analysis. Similar, but different effects were noted in development and fetal healing. Collagen types had a similar pattern in the three models, although the results demonstrated profound differences in timing and events surrounding new matrix production. The results of the wound modulation study using a cell proliferation marker, immunohistology, Western blots and zymograms of these wounds, were analysed and found to show marked differences in morphology, enzyme production and cell proliferation. The results excluded growth factors and tissue perfusion as the cause when these factors were controlled for. Significant (p<O.05) differences were observed between wounds. The novel results are discussed, showing modulation of several collagens, MMPs, TIMPs, cathepsins, growth factors and integrins during tendon healing, development and fetal healing with reference to other studies and proposals for the modulation of tendon healing principally by mechanical forces on the wound are made. The observation is made that tendon fetal and adult healing are profoundly different. This is consistent with other models of fetal healing. A novel proposal from the results based on matrix organisation is made for the dissimilar nature of adult and fetal wound healing.
7
Stevenson, John Howard. "An investigation into the effect of ultrasound on repaired tendons." Thesis, Queen's University Belfast, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335315.
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Harrison, R. "The elucidation and strategic modification of flexor tendon healing mechanisms." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445576/.
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Introduction and aims: 16,000 flexor tendon repair operations are performed annually in the UK these are frequently complicated by adhesions, causing significant morbidity. The uncertainty over which cells are responsible for the tendon healing mechanisms persists. We aimed to develop a novel experimental model to elucidate the possible role and migratory response of synovial sheath fibroblasts during tendon healing and to determine the effects of differing environment and stimuli on the cellular processes in the healing tendon. 0.1.2 Materials and methods: Rat synovial sheath cells were labelled with a lipophilic tracer dye, and an injury made in the adjacent flexor tendon. Tendons were then harvested at 1,3,5 and 7 days and frozen sectioned. The location of the labelled fibroblasts was determined using ultra-violet microscopy. In a separate experimental series, rat flexor tendons received different injury type / mobilisation or immobilisation / and TGF-pl or saline control application. Tendons were harvested at 7 and 14 days, fixed, sectioned and HandE stained. Cell densities in the injury region were determined. 0.1.3 Results: By 24 hours, labelled synovial fibroblasts were observed to have migrated from the sheath to the zone of injury, with numbers increasing at 3 and 5 days, but diminishing by day 7. In the second experimental model, tendons injured with a superficial scrape, or immobilised post-injury showed a significant increase in relative cellularity in the region of the injury. 0.1.4 Discussion: These results suggest that synovial cells are involved in the early stages of tendon healing, and migrate from the synovial sheath into the healing tendon. Fibroblast density, in the rat model, is modulated by type of injury, immobilisation, but not TGF-p 1 application. This may correlate clinically with collagen deposition and adhesion formation.
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Virchenko, Olena. "Stimulation of tendon repair by platelet concentrate, CDMP-2 and mechanical loading in animal models." Doctoral thesis, Linköping : Univ, 2007. http://www.bibl.liu.se/liupubl/disp/disp2007/med1005s.pdf.
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Kinneberg, Kirsten R. C. "Tissue Engineering Strategies to Improve Tendon Healing and Insertion Site Integration." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307106075.
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Dyment, Nathaniel A. "Using Development and Natural Healing as a Paradigm to Improve Tendon Repair." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1320083190.
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Subramanian, Gayathri Gowri. "Mechanically-Conditioned Biphasic Composite Scaffolds to Augment Healing of Tendon-Bone Interface." University of Toledo / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1500469300203445.
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Jones, Martin Edward. "The cellular mechanisms of hand flexor tendon healing and their strategic modification." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399269.
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Bajuri, Mohd Nazri Bin. "Mechanobiological analyses of healing tendons using computational approaches." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:c6daa0b7-4875-4056-b05e-c35097988b72.
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The healing process of ruptured tendons is problematic due to scar tissue formation and deteriorated material properties. In some cases, it may take nearly a year to complete. Mechanical loading has been shown to positively influence tendon healing; however, the mechanisms remain unclear. Computational mechanobiology methods employed extensively to model bone healing have achieved high fidelity, but not yet been explored to understand tendon regeneration. The general objective of this thesis is to develop computational approaches to enhance the knowledge of the role that mechanical factors play in fibre re-organisation in healing tendons, by proposing an appropriate constitutive formulation, followed by analysing the mechano-adaptation of the models created when regulated by different biophysical stimuli. Curve fitting of an established hyperelastic fibre-reinforced continuum model introduced by Gasser, Ogden and Holzapfel (GOH) against experimental tensile testing data of rat Achilles tendons at four timepoints during the tendon repair was used and achieved excellent fits (0.9903 < R<sup>2</sup> < 0.9986). A parametric sensitivity study using a three-level central composite design, which is a fractional factorial design method, showed that the collagen-fibre-related parameters in the GOH model had almost equal influence on the fitting. The mechano-adaptation of the healing tendons when regulated by axial and principal strain predicted fibre re-organisation comparable to experimental findings, in contrast to models regulated by deviatoric strain. Also, mechano-adaptive models regulated by deviatoric strain were more spatially and temporally sensitive to different boundary conditions - length and loading magnitudes - than those regulated by axial and principal strain. This thesis describes that a hyperelastic fibre-reinforced mechano-adaptive model regulated by axial or principal strain is generally capable of describing the mechanobiological behaviours of healing tendons, and that further experiments should focus on establishing the localised structural and material parameters of collagen fibres and their mechano-adaptive behaviours in the healing tissue.
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Lalley, Andrea L. "Identifying and Evaluating Novel Biological Targets to Improve Musculoskeletal Tissue Engineering Strategies." University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416231302.
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Davidson, K. Elaine. "Flexor tendon healing : evaluation of peritendinous adhesion formation and tendon strength after tenotomy and primary repair in an ovine model." Thesis, University of Edinburgh, 2006. http://hdl.handle.net/1842/29086.
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This experimental study was designed to assess the effects of different surgical repair techniques on the process of flexor tendon healing. In particular, it aimed to evaluate the effects of incorporating a novel biocompatible, biodegradable ‘wrap’ into the process of tendon repair. This inorganic polymer wrap, Controlled Release Glass (Giltech Limited, Ayr, Scotland, UK) was composed of a combination of sodium and calcium cations with phosphate and oxide anions and degraded into simple ionic substances normally found in tissue fluid. The hypothesis to be tested stated that ‘the addition of this potentially anti-adhesiogenic substance to the process of flexor tendon repair would result in no difference in musculoskeletal function or tendon characteristics after recovery’. Tenotomy and primary repair of the ovine Flexor Digitorum Superficialis (Pars Superficialis slip) was performed using a variety of different repair methods, involving combinations of the following elements of repair; modified Kessler core suture, circumferential epitenon suture, CRG wrap, triamcinolone paste. Eleven experimental groups of twelve cases were set-up and evaluated in two time cohorts; six weeks and six months after surgery. A control group of twelve non-operated cases was also assessed. Results of statistical analyses showed that for the experimental groups which incorporated CRG wrap, the proliferative vascular response to injury was diminished toward ‘normal’ range at six weeks and within ‘normal’ range by six months after repair. This occurred in the absence of any significant difference in superficial blood flow beyond the site of repair or in the strength of these groups of repaired tendons. Also, at six weeks after operation these experimental groups showed a reduction in fibrous tissue at the sites of tendon repair without any other significant differences in morphological features of the healing tendon. The implications for clinical practice of these findings are discussed.
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Al, Youha Sarah. "Towards an understanding of the mechanisms of acellular zone formation in sutured tendons." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/towards-an-understanding-of-the-mechanisms-of-acellular-zone-formation-in-sutured-tendons(a942e6b2-44e4-44dc-a949-34ce3b39e6f4).html.
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Fibrotic diseases account for an estimated 45% of the total number of deaths in the developed world (Wynn 2007). Tendons are an excellent model for studying the dysregulated response which leads to fibrosis, as tendons have an organized, parallel matrix, in which tissue defects could easily be distinguished. Wong et al. (2006b) demonstrated the presence of a bell-shaped region around sutures in tendons that was devoid of cells in histological sections. The mechanisms of the formation of this acellular zone, that was also noted in cornea and cartilage (Matsuda et al. 1999; Hunziker and Stähli 2008), were unknown. It was hypothesized that the acellular zone was formed by cell death and that suturing caused alterations to the extracellular matrix of sutured regions of tendon, which made the acellular zone refractory to cellular re-population. The acellular zone was tracked in sutured tendons for up to a year to determine the temporal properties of the acellular zone. Electron microscopic and time lapse studies were carried out to determine if the acellular zone formed by cell migration or cell death. Microarray analysis was conduced to confirm this and to reveal potential molecular targets for future studies. The extracellular matrix of sutured tendons was studied by electron, atomic, scanning and polarized light microscopy and mechanical measurements were obtained using nanoindentation. It was concluded that the acellular zone formed within 24 hours and persisted for up to a year. Tension and size of the suture's grasp were also shown to be important for acellular zone formation. Cell death was the main effector of acellular zone formation. Microarray analysis showed evidence of upregulation of inflammatory mediators and programmed necrosis pathways. The sutured extracellular matrix was denser, more disorganized and had a lower Young's modulus than unsutured regions of the same tendon. These differences in the properties of the extracellular matrix of sutured tendons may be the cause of the persistence of the acellular zone.
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Medeiros, Jordan-Ryan J. I. K. "Effects of calcium carbonate particulate releasing surgical anchors on bone and tendon healing." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/57971.
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Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2007.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (p. 31-32).<br>The Calaxo ® screw, developed by Smith and Nephew, is a novel biomedical composite composed of poly-DL-lactide-co-glycolide (PLLA:PGA) 85:15 and calcium carbonate particulates. Comparisons to an identical surgical anchor composed of PLLA, largely considered an industry standard, shows increased mean failure strength in surgical reconstructions of the patellar-tibia complex in sheep. SEM imaging confirms the osteoconductivity of the Calaxo ® screw proposed in previous studies and also suggest a positive effect on the differentiation of tissues along the tendon-bone interface. These findings support the intended use of the Calaxo ® screw as a fixation device for rotator cuff repair procedures.<br>by Jordan-Ryan J.I.K. Medeiros.<br>S.B.
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Malis, Emma. "The Effect of Mechanical Stimuli on Healing Achilles Tendons in Rats." Thesis, Linköping University, Department of Physics, Chemistry and Biology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-19329.
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<p>Tendon healing is a slow process and the tendon may not regain its initial mechanical properties after rupture. Mechanical stimuli have shown to have positive effect on tendon healing. This study is the first to investigate the effect of vibration stimuli on healing tendons. Vibration was also compared to treadmill running, which has previously been used for mechanical stimuli.63 female Sprauge-Dawley rats were used. A 3 mm segment was removed from the Achilles tendon and the tendon was left to heal. The animals were subjected to 15 min of daily exercise, vibration or treadmill running or acted as controls without exercise. The study was divided into three experiments. Experiment 1; the animals had full time cage activity and was randomized into running, vibration and control group. Experiment 2; the animals were unloaded and randomized into vibration, running and control group. There was also a control group with full time cage activity in experiment 2. Experiment 3; the animals were unloaded and randomized into vibration and placebo group. 14 days after surgery the animals were killed and mechanical testing of the Achilles tendons was performed. The results showed no significant difference between the groups in experiment 1. Experiment 2 showed that controls with full time cage activity had higher peak load, stiffness and cross sectional area than unloaded running, vibration and control groups. In experiment 3, there was no significant difference between vibration and placebo group. In conclusion, this study shows that vibration, as applied here, does not affect tendon healing.</p>
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Khatibzadeh, Sarah M. "Porcine urinary bladder matrix in an in vitro equine model of tenogenesis." Thesis, Virginia Tech, 2019. http://hdl.handle.net/10919/93224.
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Extracellular matrix (ECM) is responsible for tendon strength and elasticity. Healed tendon ECM lacks structural integrity, leading to reinjury. Porcine urinary bladder matrix (UBM) provides a scaffold and source of bioactive proteins to improve tissue healing, but has received limited attention for treating tendon injuries. The objective of this study was to evaluate the ability of UBM to induce matrix organization and tenogenesis using a novel in vitro model. We hypothesized that addition of UBM to tendon ECM hydrogels would improve matrix organization and cell differentiation. Hydrogels seeded with bone marrow cells (n = 6 adult horses) were cast using rat tail tendon ECM ± UBM, fixed under static tension and harvested at 7 and 21 days for construct contraction, cell viability, histology, biochemistry, and gene expression. By day 7, UBM constructs contracted significantly from baseline, whereas control constructs did not. Both control and UBM constructs contracted significantly by day 21. In both groups, cells remained viable over time and changed from round and randomly oriented to elongated along lines of tension with visible compaction of the ECM. There were no differences over time or between treatments for nuclear aspect ratio, DNA, or glycosaminoglycan content. Decorin, matrix metalloproteinase 13, and scleraxis expression increased significantly over time, but not in response to UBM treatment. Mohawk expression was constant over time. Cartilage oligomeric matrix protein expression decreased over time in both groups. Using a novel ECM hydrogel model, substantial matrix organization and cell differentiation occurred; however, the addition of UBM failed to induce greater matrix organization than tendon ECM alone.<br>Master of Science<br>Tendon injuries are common in horses and are painful and can be career- and life-ending. Tendons have a special structure and organization that enables them to withstand high tensile forces without permanent deformation. Injured tendons heal by forming stiff, disorganized scar tissue that makes the tendon more prone to re-injury. The lining of urinary bladders from pigs (UBM) provides a physical mesh and signaling factors that help heal injuries in a variety of tissues to a more normal state. However, UBM has not been evaluated in a laboratory model of tendon tissue formation to determine how it can help heal tendon injuries. Three-dimensional models of new tendon tissue formation (neotendons) were made with rat tail tendon matrix and stem cells collected from horse bone marrow. The neotendons were placed under steady tension for 3 weeks. The models were collected after 1 and 3 weeks to measure their width, numbers of live cells, cell and matrix organization, levels of tendon matrix components and expression of genes found in tendons. Most cells in the neotendons remained alive during the study period. Over time, UBM-treated and untreated neotendons became narrower compared to their starting width. The width of UBM-treated neotendons decreased faster than non-treated neontendons in the first week of the study. Cells became longer, narrower, and oriented along lines of tension. Expression of genes important in tendon development and structure either increased or was constant over time. UBM treatment did not change cell shape or increase levels of tendon-associated genes, DNA, or tendon matrix components. Our novel tendon model successfully created organized tendon-like tissue when placed under tension. However, UBM treatment did not improve formation of tendon-like tissue to a greater extent than controls.
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Thangarajah, T. "Augmentation of rotator cuff tendon-bone healing using demineralised bone matrix and mesenchymal stem cells." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/10027670/.
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BACKGROUND: The results of surgery for tears of the rotator cuff are variable, with failure occurring in up to 94% of cases. Demineralised bone matrix (DBM) consists of a collagen scaffold containing multiple growth factors and has been used successfully to improve tendon-bone healing. By combining DBM with stem cells its effects may be enhanced given that many of the growth factors it contains are able to direct stem cell differentiation down tenogenic, chondrogenic, and osteogenic lineages. These cell lines produce elements essential to the formation of a naturally graded enthesis. AIM: To investigate the effect of DBM on regeneration of the tendon-bone interface, and whether its function can be enhanced by mesenchymal stem cells (MSCs). HYPOTHESIS: DBM will improve tendon-bone healing in an enthesis defect model, and its effect may be further enhanced by the incorporation of MSCs. METHODS: The following experiments were undertaken in order to investigate the hypothesis: 1. Tensile testing of allogenic and xenogenic cortical/cancellous DBM. 2. Evaluating the effect of allogenic and xenogenic DBM, incorporated with MSCs, on regeneration of the enthesis in a large animal model of severe tendon retraction. 3. Development of a chronic rotator cuff tear model. 4. Investigation of tendon-bone healing using DBM in a chronic rotator cuff tear model. 5. Investigation of tendon-bone healing using DBM and MSCs in a chronic rotator cuff tear model. RESULTS: Allogenic cortical DBM possessed the greatest tensile strength and was used in vivo to examine tendon-bone healing complicated by retraction. In this, DBM regenerated a direct enthesis characterised by fibrocartilage. A similar effect was noted in a chronic rotator cuff tear model with no additional effect conferred by the stem cells. CONCLUSION: This thesis has shown that DBM can regenerate a fibrocartilaginous enthesis in models of tendon retraction and chronic rotator cuff degeneration.
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Brown, Phillip G. M. "2D ultrasound elastography as a functional measure of healing of the Achilles tendon in vivo." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:e2d0a97e-d557-4b5a-869a-36cbd33b9994.
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The Achilles tendon is the largest tendon in the human body, which elastically stores and releases energy to facilitate walking and running. Tendons can suffer from a range of pathologies, most notably that of complete rupture, which affects athletes, physically active workers and the aged. There is a growing demand for in vivo methods of objectively measuring tendon health for aiding diagnosis, monitoring therapy and for assessment of new treatments. Knowledge of the changes in mechanical properties during the healing process is also limited and new methods to accurately and consistently estimate these could provide insights into the healing process and guide future research efforts. This thesis presents the development and use of 2D ultrasound elastography, a quantitative strain estimation imaging technique, as a tool to measure changes in the tensile mechanical properties of the Achilles tendon. This technique performs frame-to-frame block matching of image texture to track motion in an ultrasound signal sequence and create a strain estimation field from the spatial derivative of the motion. Elastography in the image-lateral direction of sagittal plane scans is of particular interest as this is in line with the longitudinal axis of the tendon, but presents extra accuracy issues from out of plane motion and lower image spatial resolution. Tendon rupture also presents unique problems to image acquisition and analysis- patient pain and safety are important considerations and disruption of the ultrasound texture can make 2D motion tracking more difficult. A new 2D elastography block matching algorithm, named `AutoQual', was developed to enable accurate tracking of motion in the image-lateral direction and reduce the impact of artefacts and errors common with damaged Achilles tendons image sequences. It was shown to outperform a multiscale block matching method when tested using ultrasound sequences from in vivo and gelatine phantom experiments. The input parameters of this algorithm were then optimised using the phantom data for benchmarking. The AutoQual algorithm was then used to analyse ultrasound sequences from a 24-week longitudinal study of 21 subjects with ruptured Achilles tendons to assess lateral, axial and principal strains during controlled passive motion of the foot or axial palpation of the ultrasound probe. Lateral and principal strains from controlled dorsiflexion were shown to be more repeatable and more sensitive to change than axial strains with manual palpation. This experience with lateral strain imaging from ruptured Achilles tendons gave an increased knowledge of the strain imaging artefacts and features that can occur. These are described in detail in order that they may be further mitigated in quantitative analysis by optimising acquisition protocols, further amendment of the block tracking algorithm, or exclusion of erroneous areas when selecting regions of interest. Regularisation is a potential solution to some common artefacts such as discontinuities from poor tracking in shadow regions. Regularisation of the lateral displacement fields is investigated using 2D bicubic smoothing splines. The regularisation parameters used are shown to have minimal effect on quantitative analysis and can aid visual clarity or reduce artefacts within certain settings. However, regularisation was also shown to cause large errors when parameters were set more aggressively. Finally, it is identified that cumulative lateral strain measurement of the Achilles and other tendons is feasible but that future work is needed to further improve the quality of force and cross sectional area measurements in order to infer mechanical properties accurately. Repeatable high force motion protocols also need to be developed to measure healthy tendons and to ensure comparable results between different patients and research groups.
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Junior, Edson Alves de Barros. "Os efeitos do ultra-som na cicatrização de tendões flexores de coelhos após tenorrafia." Universidade de São Paulo, 2001. http://www.teses.usp.br/teses/disponiveis/82/82131/tde-07112001-090924/.
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A utilização do ultra som com a finalidade de acelerar o reparo tecidual é muito freqüente na prática clínica, embora as bases científicas para sua utilização não estejam bem estabelecidas. Este estudo analisou os efeitos do ultra som na cicatrização de tendões flexores de coelhos após tenorrafia. Foram utilizados 30 coelhos da raça Nova Zelândia, com peso médio de 2,7 Kg, divididos em dois grupos de 15 animais submetidos a tenotomia e tenorrafia com sutura tipo Kessler do tendão flexor profundo do terceiro dedo da pata dianteira direita. Após 24 horas foi iniciado em um dos grupos tratamento com ultra som, sendo o outro grupo utilizado para controle. A freqüência utilizada foi a de 3 MHz e a intensidade de 0,8 W/centímetro quadrado (SATA), por contato direto durante 7 dias consecutivos. Cada grupo foi dividido em subgrupos com 5 animais cada, e estes sacrificados em períodos distintos (8, 15 e 30 graus PO), e o tendão operado, dissecado e submetido à análise histológica pela microscopia de luz, analisando a reação inflamatória, grau de necrose, proliferação de fibroblastos, deposição de colágeno e formação de granuloma. Os resultados mostraram que o ultra som interferiu com o processo de reparo tecidual após a tenorrafia dos tendões flexores de coelhos<br>The use of ultrasound aiming to accelerate tissue healing is very frequent in clinical pratice, although the scientific basis to its use are not well established. This study analized the effects of ultrasound on the healing of rabbits flexor tendons after repair. It was used 30 New Zealand rabbits, with an average weight of 2.7 Kg, divided in two groups of 15 animal. They were submetted to tenotomy and repair with Kesslers suture on deep flexor tendon of the middle right front claw. After 24 hour one of the groups started the ultrasound treatment, and the other was de control group. The ultrasound frequency used was 3 MHz and the intensity was 0.8 W/square cemtimeter (SATA), by direct contact during 7 consecutive days. Each group was divided in subgroups with 5 animals each, and these were killed in distincts periods (PO 8, 15 and 30), and the operated tendon was dissected and submitted to histologic analises by light microscopy, anlaysing the inflammatory reaction, necrosis degree, fibroblasts proliferation, colagen synthesis and granulom formation. The result showed that ultrasound interfere on the tissue healing process after repair on the rabbits flexor tendons
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Gilday, Steven. "The Therapeutic Potential of Indian Hedgehog (Ihh) for Tendon-to-Bone Repair." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460731518.
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Cao, Yi, and 曹怡. "Investigation of expression of extracellular matrix component genes during tendon healing process: an in vivochicken study." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42182414.
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Louie, Libby K. "Effect of a porous collagen-glycosaminoglycan copolymer on early tendon healing in a novel animal model." Thesis, Massachusetts Institute of Technology, 1997. http://hdl.handle.net/1721.1/43367.
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Estrada, Roberto J. [Verfasser]. "Healing Characterization of Surgically Induced Core Lesions of the Equine Superficial Digital Flexor Tendon / Roberto J. Estrada." Berlin : Freie Universität Berlin, 2014. http://d-nb.info/106036784X/34.
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Cao, Yi. "Investigation of expression of extracellular matrix component genes during tendon healing process an in vivo chicken study /." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42182414.
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Pasternak, Björn. "Towards surgical use of matrix metalloproteinase biology /." Linköping : Department of Clinical and Experimental Medicine, Linköping University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-11489.
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Romano, Cristiane Vitaliano Graminha. "Os efeitos do ultra-som terapêutico aplicado na fase precoce da cicatrização do tendão flexor. estudo biomecânico em tendões de coelho." Universidade de São Paulo, 2001. http://www.teses.usp.br/teses/disponiveis/82/82131/tde-12092001-093542/.
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Foi realizado um estudo experimental dos efeitos do ultra-som terapêutico sobre a resistência à tração de tendões flexores em cicatrização, usando o tendão flexor dos dedos de coelho como modelo. Foram utilizados 25 coelhos fêmea, da raça Nova Zelândia, adultos jovens de 3 Kg de peso corporal médio. Todos os animais foram operados sob anestesia geral para terem o tendão flexor profundo do terceiro dedo da pata dianteira direita seccionado e imediatamente reparado com a técnica de Kessler. As patas operadas eram imobilizadas com uma órtese de material termoplástico durante todo o período do experimento (4 semanas) e os animais foram distribuídos em dois grupos ( A e B) de acordo com o tratamento pós-operatório. No grupo A (13 animais) todos os animais receberam uma aplicação diária de 6 minutos de duração de ultra-som pulsado (1:5), regulado para uma freqüência de 3 MHz e intensidade de 0,8 W/cm², por sete dias consecutivos começando do primeiro dia. O grupo B (12 animais) era apenas de controle. Quatro semanas mais tarde, os animais eram mortas e todo o tendão operado era ressecado, incluindo a junção miotendínea e o segmento distal, e submetidos aos testes de resistência à tração na máquina universal de ensaios. Gráficos das cargas versus a deformação foram obtidos, permitindo a análise dos parâmetros carga e deformação máximas, carga e deformação no limite de proporcionalidade e rigidez. Os resultados mostraram que não houve diferenças significantes entre os grupos A e B, levando à conclusão de que o ultra-som terapêutico não tem influência no curso do processo de cicatrização dos tendões, particularmente no que se refere à resistência mecânica.<br>An experimental study of the effects of the therapeutic ultrasound on the resistance to traction of healing flexor tendons carried out using the rabbit flexor tendon as model. Twenty five young adult female New Zeland rabbits of average 3 Kg body weight were used. All the animals were operated under general anesthetics to have the profundus flexor tendon of the third finger of the right forepaw divided and immediately repaired with Kessler technique. The operated on paw was immobilized with an orthesis made of thermoplastic material for the entire length of the experiment (four weeks) and the animals were divided in two groups (A and B), according to the postoperative treatment. In group A (13 animals) all animals received one 6 minutes daily application of pulsed ultrasound (1:5), set for 3 MHz frequence and 0,8 W/cm² intensity, for seven consecutive days beginning on the first postoperative day. Group B (12 animals) was for control only. Four weeks later, the animals were killed, the entire operated tendons were resected including the myotendinous junction and the distal segment and submitted to the test of resistance to traction in a universal testing machine. Load versus deformation graphs were obtained allowing for the analysis of the parameters maximum load and deformation, load and deformation in the limit of proportionality, and stiffness. The results showed that there was no significant difference between groups A and B, leading to the conclusion that therapeutic ultrasound does not influence the course of the tendon healing process, as refers to mechanical resistance.
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Empson, Yvonne Marie. "Developing a Living Composite Ligament by Combining Prolotherapy and Nanoparticles as Treatment for Damaged Connective Tissue." Thesis, Virginia Tech, 2014. http://hdl.handle.net/10919/78114.
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Significant cost and debilitation results from connective tissue injury and disease every year. Prolotherapy is an effective medical treatment used to increase joint stability. However, most associated studies are retrospective or case studies, rather than comprehensive laboratory investigation originating with the cellular response to exposure to the proliferant solutions. As a parallel consideration, nanoparticles are being investigated for use in drug delivery and heat shock treatment of cancerous tissue due to their unique structural and thermal properties. The phenomenal strength and stiffness of carbon nanoparticles have been used for commercial purposes in composite materials, but investigation of biomedical applications is still fairly nascent. In an attempt to develop a non-surgical approach to supporting and healing damaged ligaments and tendons resulting from injury or disease by combining prolotherapy and the use of nanoparticles, the author presents studies investigating the cellular response to proliferative therapy solution as well as tendon and ligament tissue's mechanical and cellular response to exposure to nanoparticles. In the prolotherapy solution cell studies, the results suggested that there is an optimal dosage of the proliferant for in vitro studies, different responses between cell types, and a dosage-dependent response in cell viability and collagen production to the solution P2G in preosteoblasts. In the nanoparticle studies, cell populations tolerated nanoparticles at the levels tested, tendon mechanical properties were increased (stiffness significantly so), and bright field and transmission electron microscopic histological images were taken of connective tissue and carbon nanohorn interactions.<br>Master of Science
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Bastos, Jessica Lucia Neves. "Estudo comparativo de sistemas a base de lasers, leds e ultra-som (US) de baixa intensidade no reparo tecidual em tendão calcâneo." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/82/82131/tde-16102008-121005/.
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Um dos recursos mais utilizados no processo de reparo de lesões tendíneas é o laser que demonstrou ter resultados satisfatórios quando se buscam efeitos antiinflamatório e cicatrizante. No entanto, por requerer uma tecnologia de alto custo, um outro tipo de fototerapia vem sendo buscado, como o diodo emissor de luz, LED. Porém, o número de pesquisas realizadas para a determinação segura de seus efeitos terapêuticos ainda é muito pequeno, inviabilizando uma proposta de protocolo para adoção do LED. Um outro recurso também utilizado durante a reabilitação de lesões tendíneas, é o ultra-som pulsado de baixa intensidade (LIPUS). Trabalhos realizados até o momento mostram alterações satisfatórias quanto à deposição e alinhamento das fibras de colágeno. Este estudo objetiva testar comparativamente a eficácia da aplicação de LEDs 630 nm e 830 nm em relação à terapia laser de baixa intensidade (LILT), com laser de 685 nm e 830 nm, e à terapia com LIPUS em tendão calcâneo parcialmente lesado. Foram utilizados 56 ratos Wistar, submetidos à lesão mecânica parcial do tendão calcâneo. A análise da evolução do processo foi realizada através da microscopia de polarização. Os resultados mostraram uma real eficácia dos tratamentos com LEDs e lasers, e uma ineficácia do tratamento à base de US. Nosso estudo sugere que uma boa organização e um bom alinhamento das fibras de colágeno são conseguidos no processo de reparo de lesões tendíneas através de aplicações à base de LED 880 nm e laser 630 nm, os quais se mostraram mais eficazes. No entanto, outras pesquisas na área se fazem necessárias para uma determinação segura e eficaz dos protocolos de tratamento utilizando essa modalidade de fototerapia.<br>Laser is one of the most effective resources of treatment for tendinous injury when anti-inflammatory and cicatrizing effects are wanted. However, it is considered an expensive treatment and so, an alternative and cheaper light therapy as effective as it has been searched and the light emitting diodes, LEDs, are a promising candidate for it. Results from the studies already done have been useful to predict the possible effects of LED on the injured tissues, but are not enough to establish a treatment protocol that guarantees its recommendation as a substitute therapeutic tool for tendinous injury treatment. Another promising resource for tendinous injury healing is the ultra-sound of low intensity (LIPUS). Studies done until the present moment have shown satisfactory results when deposition and alignments of collagens fibers are wanted. The aim of this study was to compare the effects of laser, light emitting diodes (LEDs) and ultra-sound of low intensity on the treatment of Achilles tendon of albino rats, Wistar lineage, exposed to mechanical trauma. The experimental model consisted of a partial mechanical lesion of the right Achilles tendon of 56 rats, which were divided in 6 groups, 5 with 10 animals and one, the control group, with 6. One hour after the lesion, the injured animals received the respective applications of laser, LED or US, and the same procedure was repeated each 24 h. The healing process and the deposition were evaluated by analyze of the alignment of collagens fibers through polarization microscopy. The results showed a real efficiency of treatments based on LEDs and lasers, but the treatment based on US was inefficient. Applications of laser at 830 and LED 880 nm were more efficient when the aim is a good organization and alignment of the collagen fibers on tendon healing. However more research is needed for a safety and more efficient determination of a protocol.
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Gaut, Ludovic. "Mechanical and molecular signals underlying tendon cell differentiation." Electronic Thesis or Diss., Sorbonne université, 2018. http://www.theses.fr/2018SORUS301.
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Les tendons sont une forme unique de tissu conjonctif au sein du système musculosquelettique. Le développement, l’homéostasie et la réparation du tendon reposent sur des combinaisons de paramètres moléculaires et aussi mécaniques, régulant la production et l’assemblage des fibres de collagène. Notre objectif est de comprendre quelles sont les voies de mécanotransduction impliquées dans la différentiation tendineuse, via deux (co-)facteurs de transcription : EGR1 et YAP. Nous avons montré que l’expression du gène de tendon SCX, de EGR1 et l'activité de YAP sont réduites dans les tendons de membres de fœtus de poulet immobilisés. De plus, la reprise des contractions musculaires entraîne une reprise de l’expression des gènes de tendon comparable à celle des fœtus jamais immobilisés. La mécanobiologie du tendon a été étudiée avec des constructions cellulaires en 3-dimensions (3D) en gel de fibrine ou de collagène, faits de cellules souches mésenchymateuses. La perte de tension de ces constructions a induit une chute de l’expression de Egr1, des gènes de tendon et de l’activité de YAP. Une surexpression de Egr1 dans les constructions 3D en gel de fibrine sans tension a empêché la chute d’expression des gènes de tendon. L’activité de YAP et l’expression de Scx ont augmenté en étirant les constructions en gel de collagène. L’inactivation de l’activité de YAP par traitement à la verteporfin (VTPF) a induit une diminution de l’expression des gènes de tendon, qui n’a pas été restaurée lorsque ces constructions traitées ont été étirées. Ensemble, ces résultats montrent l’importance de YAP et EGR1 en aval des signaux mécaniques pour réguler la différentiation des cellules du tendon<br>Tendons are unique forms of connective tissue of the musculoskeletal system. Tendon development, homeostasis and repair rely on specific combinations of mechanical and molecular factors regulating the production and assembly of collagen fibers. Our objective is to decipher the mechanotransduction pathways underlying tendon cell differentiation, through the activity of two transcription (co-)factors, EGR1 and YAP. We showed that the expression of the tendon gene SCX, the mechanosensitive gene EGR1 and YAP activity were downregulated in limb tendons of immobilized chicken fetuses. Restored muscle contraction after immobilization led to a recovery of tendon gene expression. Tendon mechanobiology was studied in vitro in fibrin- or collagen-based 3-dimensional (3D) constructs made of mesenchymal stem cells and mimicking tendon formation. Tension release in fibrin and collagen 3D-constructs induced a drop of the expression of Egr1, tendon genes and YAP activity. Overexpression of Egr1 was able to prevent the downregulation of tendon gene expression in de-tensioned fibrin 3D-constructs. YAP activity was upregulated in dynamically stretched collagen 3D-constructs and was paired with the expression of the tendon gene Scx. Chemical knock-down of YAP activity with Verteporfin (VTPF) treatment showed a decrease in the expression of YAP target genes and the tendon genes. Besides, dynamic stretch applied on VTPF-treated constructs did not restore tendon gene expression, conforting the role of YAP as an intracellular relay of mechanical cues in tendon cells. Altogether, these results highlight the importance of EGR1 and YAP downstream of mechanical forces during tendon cell differentiation
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Chokalingam, Kumar. "Transgenic Mouse Model: Examination of Healing, Development and Mechanical Response of Cells." University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1259076989.
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Lin, Dasheng [Verfasser], and Denitsa [Akademischer Betreuer] Docheva. "Unravelling the roles of tenomodulin at the nexus of early tendon healing and intervertebral disc homeostasis / Dasheng Lin ; Betreuer: Denitsa Docheva." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1222909154/34.
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Hsieh, Chi-Fen [Verfasser], and Denitsa [Akademischer Betreuer] Docheva. "Advancing tendon healing by scaffolds-free delivery of different subtypes of mesenchymal stem or progenitor cells / Chi-Fen Hsieh ; Betreuer: Denitsa Docheva." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1158496095/34.
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Seto, Song P. "The development of heparin-based materials for tissue engineering applications to treat rotator cuff tendon injuries." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/51898.
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Surgical repair of torn rotator cuff tendons have a high rate of failure and does not address the underlying pathophysiology. Tissue engineering strategies, employing the use of multipotent progenitor cells or growth factors, represent potential therapies to improve the outcome of rotator cuff surgery. The use of glycosaminoglycan-based biomaterials in these therapies may enhance the effectiveness of cell and growth factor delivery techniques. Furthermore, understanding the cellular and molecular mediators in tendon overuse can help elucidate the causes of tendon degeneration. Thus the overall goals of this dissertation were to 1) develop heparin-based biomaterials to enhance cell pre-culture and maintain growth factor bioactivity and 2) characterize the histological and enzymatic changes in a supraspinatus tendon overuse model. To investigate the use of heparin in enhancing dynamic signaling, mesenchymal stem cells (MSCs) were encapsulated in heparin-containing hydrogels and evaluated for differentiation markers when cocultured with a small population of differentiated cells. To probe the effect of sulfation of heparin on the interactions with protein, selectively desulfated heparin species were synthesized and evaluated for their ability to bind and protect proteins. Finally, to develop a tendon overuse model that can become a test bed for testing future targeted therapeutics, an animal model was evaluated for tissue damage and protease activity. Together these studies represent a multi-pronged approach to understanding how tendon tissues become degenerative and for developing technologies to improve the biological fixation of tendon to bone in order to reduce the need for revision surgeries.
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Aro, Andrea Aparecida de 1980. "Efeito dos extratos de Aloe vera e Arrabidaea chica sobre a cicatrização do tendão calcanear de ratos após transecção parcial." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317389.
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Orientador: Edson Rosa Pimentel<br>Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-21T05:39:03Z (GMT). No. of bitstreams: 1
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Previous issue date: 2012<br>Resumo: A utilização de extratos vegetais com atividades farmacológicas pode ser promissora no tratamento de lesões tendíneas, considerando a presença de princípios ativos que estimulam a síntese de componentes da matriz extracelular (MEC). Portanto, o presente estudo teve como objetivo investigar após 7, 14 e 21 dias da lesão, os efeitos da aplicação tópica dos extratos de A. vera e A. chica sobre tendões parcialmente transeccionados de ratos. Os grupos tratados com o extrato da A. chica foram denominados A7, A14 e A21 (controles S7, S14 e S21), e após tratamento com a A. vera foram denominados Av7, Av14 e Av21 (controles B7, B14 e B21). Foram realizadas análises bioquímicas tais como Western blotting, zimografia e dosagens de hidroxiprolina, de proteínas não colagênicas (PNCs) e de glicosaminoglicanos (GAGs); assim como análises estruturais, ultraestruturais e funcionais. Após aplicação do extrato da A. chica, a concentração de PNCs foi menor em A7 e a de hidroxiprolina foi maior em A7 e A21, em relação aos controles. Considerando a MMP-9, menor quantidade foi detectada no grupo A14 comparado ao grupo S14. As isoformas latente, intermediária e ativa da MMP-2 foram observadas em todos os grupos, porém maiores quantidades das isoformas latente e intermediária foram encontradas em A21. Os resultados de Western blotting mostraram menor quantidade de colágenos tipos I e III em A7 comparado ao controle. Maior quantidade de dermatan sulfato (DS) foi detectada em A14, e quantidade inferior de DS e condroitin sulfato (CS) foi observada em A21 comparada ao S21. As medidas de birrefringência detectaram maior organização das fibras de colágeno no grupo A21 em relação ao controle, e as análises ultraestruturais mostraram muitos fragmentos de colágeno na região transeccionada nos grupos S7 e A7. A análise do CatWalk mostrou que os animais tratados com A. chica, exibiram maior pressão de contato das patas durante a marcha no 7° dia. Considerando a aplicação de A. vera, foi observada em SDS-PAGE banda menos intensa referente ao colágeno em Av14, confirmado por Western blotting. O grupo Av21 apresentou maior concentração de PNCs comparado ao seu controle. Na dosagem de hidroxiprolina, os grupos Av7 e Av14 apresentaram maiores concentrações, ao passo que Av21 apresentou valor inferior ao controle. O grupo Av14 apresentou maior concentração de GAGs sulfatados e menor quantidade de DS em relação ao controle. Menor quantidade de MMP-9 foi encontrada em Av14, e menores quantidades das isoformas latente e intermediária da MMP-2 foram observadas em Av7 e Av14 em relação aos controles. Maior quantidade da isoforma ativa da MMP-2 foi observada em Av21 comparado a B21. As medidas de birrefringência detectaram maior organização das fibras de colágeno em Av14 em relação ao controle. Ao passo que as medidas de dicroísmo linear realizadas nos cortes corados com azul de toluidina, mostraram menor organização dos GAGs em Av14 comparado ao controle. Nossa conclusão é que a aplicação tópica dos extratos da A. chica e da A. vera é efetiva na síntese e organização de componentes da MEC durante o processo de reparo<br>Abstract: The use of plant extracts bearing pharmacological activities may be promising in the treatment of tendon injuries, considering the presence of active principles that stimulate the synthesis of extracellular matrix components (ECM). Therefore, this study aimed to investigate after 7, 14 and 21 days of injury, the effects of topical application of extracts of A. vera and A. chica on the healing of partially transected tendons of rats. The groups treated with the extract of A. chica were called A7, A14 and A21 (controls S7, S14 and S21), and after treatment with A. vera were called Av7, Av14 and Av21 (controls B7, B14 and B21). Biochemical analysis were performed such as Western blotting, zymography and quantification of hydroxyproline, non-collagenous proteins (NCPs) and glycosaminoglycans (GAGs); as well as structural, ultrastructural and functional analysis. After application of the extract of A. chica, the concentration of non-collagenous proteins (NCPs) was lower in A7 and hydroxyproline was higher in A7 and A21, compared to controls. Considering the MMP-9, lower amount was found in A14 compared to S14. The latent, intermediate and active isoforms of MMP-2 were observed in all groups, but larger quantities of latent and intermediate isoforms were found in A21. The results of Western blotting showed a lower amount of collagen types I and III compared to the control A7. Higher amount of dermatan sulphate (DS) was detected in A14 and lower amounts of DS and chondroitin sulfate (CS) were observed in A21 compared to S21. The birefringence measurements showed a higher organization of collagen fibers in the A21 group compared to control, and ultrastructural analysis showed many fragments of collagen in the transected region of groups S7 and A7. Analysis of the Catwalk showed that animals treated with A. chica exhibited a higher contact pressure of the legs during walking on the 7th day. Considering the application of A. vera, less intense band related to collagen was observed on SDS-PAGE in Av14, confirmed by Western blotting. The group Av21had a higher concentration of NCPs compared to the control. In the dosage of hydroxyproline, Av7 and Av14 groups had higher concentrations in relation to their controls, while Av21 showed lower value than control group. The group Av14 had a higher concentration of glycosaminoglycans and lower amount of DS compared to control. Lower amount of MMP-9 was found in Av14, and lower amounts of intermediate and latent isoforms of MMP-2 were observed in Av7 and Av14 compared to controls. A higher amount of the active isoform of MMP-2 was observed in Av21 compared to B21. The birefringence measurements showed a higher organization of collagen fibers in Av14 compared to control. While linear dichroism measurements performed on sections stained with toluidine blue, showed lower organization of glycosaminoglycans in Av14 compared to control. Our conclusion is that the topical application of extracts of A. chica and A. vera is effective in the synthesis and organization of ECM components during the repair process<br>Doutorado<br>Biologia Celular<br>Doutor em Biologia Celular e Estrutural
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Riley, Christopher Bruce. "Intrinsic healing in the equine superficial digital flexor tendon in vitro, effects of hyaluronate and polysulfated glycosaminoglycans on matrix synthesis and cell proliferation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ27427.pdf.
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Farcic, Thiago Saikali. "Efeitos de diferentes tempos de aplicação do ultrassom terapêutico no tratamento de tendão de ratos no processo de reparação tecidual." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5163/tde-03012012-080324/.
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O objetivo deste estudo foi avaliar o efeito de diferentes tempos de tratamento do ultrassom terapêutico na cicatrização de lesão tendínea. Quarenta ratos machos Wistar (300 ± 45g), dos quais 32 sofreram tenotomia do tendão do calcâneo, foram divididos em 5 grupos: grupo C, sem tenotomia e tratamento, grupo T, com tenotomia e sem tratamento, US1,US2 e US3 submetidos à tenotomia e tratados com UST nos tempos de 1, 2 e 3 minutos por área de transdutor. Os animais foram mortos no 12º dia pósoperatório e os tendões retirados cirurgicamente para análise da organização das fibras colágenas utilizou-se o método de birrefringência (retardo óptico - OR). As fibras colágenas mostraram melhor agregação e organização no grupo US3 quando comparado ao grupo T (p<0.05). Concluise que o UST, aplicado no tempo de 3 minutos por área tratada, melhorou a organização das fibras colágenas no reparo tecidual de tendões de ratos<br>The aim of this study was to evaluate the effects of different treatment times of therapeutic ultrasound (US) on tendon injury healing. Forty male Wistar rats were selected (300 ± 45g) and 32, who underwent tenotomy of the Achilles tendon, were divided into five groups: Control, without tenotomy nor any treatment; tenotomy group, with tenotomy and without treatment; US groups (US1, US2, and US3), submitted to tenotomy and treated respectively with US for one, two, and three minutes per area of the transducer. The animals were sacrificed on the 12th post-operative day and the tendons were surgically removed for analyses of the collagen fiber organization by means of birefringence analyses, or optical retard. The collagen fibers showed better aggregation and organization in the US3 group, compared to the tenotomy group (p<0.05). The findings indicated that the US applied for three minutes per treated area improved the organization of the collagen fibers in the tendon repair of rats
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Chapman-Jones, David. "The Achilles tendon : an evaluation of the healing processes occuring with chronic pathology : using a prospective comparison study of conservative treatment regimes and micro-current application." Thesis, City University London, 1998. http://openaccess.city.ac.uk/7568/.
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Muscles enable the skeleton to move. Muscles are attached to bones via tendons. Inappropriate stress placed upon the muscular-skeletal system, for example sporting activities for which the subject Is untrained, can result in Injuries which may occur either in the muscle, muscle-tendinous junction or the tendon tissue itself. The resultant pathology can often result in loss of strength or pain in the area. The healing processes of tendon tissue are not well understood and the difficulty In the clinical management of pathology reflects this. Current treatment of this type of Injury Is dependent upon the severity of the injury, its site of occurrence and the practitioners preference of treatment modality. The purpose of the study was to evaluate, following the application of micro-current for therapeutic purposes, the functional outcome In patients presenting with chronic pathology in the Achilles tendon in comparison with the current conservative management. A prospective comparison study was undertaken utilising a blocked randomisation method. Subjects were allocated to either group A and were exposed to current clinical management or group B the experimental micro-current regime. Classification and subsequent evaluation of pathology was assessed employing clinical assessment and tests; subjective assessment by the subject and assessment by diagnostic ultrasound. Subjects were assessed at three, six and twelve month intervals post entry into the study. Forty eight subjects, twenty four in each group completed the study. A statistical analysis was performed, calculating the differences between the two groups and between each interval assessment. Categorical variables were compared between the two groups using the Chi-squared test. The Mann-Whitney test was performed to assess changes in ordinal variables. The Spearman rank correlation test was used to test for correlation between age and changes in the variables. Statistically significant differences were found In favour of group B, the experimental group, in four out of the five clinical markers used. No difference was found between age or sex and the changes recorded. It was concluded that the appropriate application of micro-current treatment to the Achilles tendon presenting with chronic pathology can make a significant contribution to the clinical management of the condition. This has the Implication that a degenerative cycle promotes chronic pathology occurring In the Achilles tendon. In order to narrow the gap between the clinical and experimental findings an examination of in-vitro applications was undertaken with laboratory work undertaken evaluating the effect of micro-current stimulation on 3T3 mouse and human tendon fibroblast proliferation. The results showed that the cells stimulated with 40pA proliferated at a greater rate than the non-stimulated control group. Stimulating the cells with 1pA suppressed activity with a suppression in proliferation.
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Almeida, Marcos dos Santos de 1980. "O efeito da eletroacupuntura nos pontos Zusanli (E-36) e Chengshan (B-57) sobre o processo de cicatrização do tendão calcâneo de ratos após tenotomia parcial = uma análise bioquímica e morfológica." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317411.
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Orientador: Edson Rosa Pimentel<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-17T20:40:15Z (GMT). No. of bitstreams: 1
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Previous issue date: 2011<br>Resumo: A eletroacupuntura (EA) tem sido utilizada amplamente para o tratamento de uma variedade de doenças inflamatórias e para o alivio da dor. No entanto, não há relatos na literatura sobre o efeito da EA na composição e organização da matriz extracelular (MEC) de tendões em processo de cicatrização. Objetivo: Investigar através de análises bioquímicas e morfológicas, o efeito da EA durante o pico de síntese dos componentes da MEC, 15 dias após transecção parcial do tendão calcâneo de ratos. Materiais e Métodos: Ratos Wistar machos com 60 dias de idade foram divididos em 3 grupos: Não tenotomizados (G1), tenotomizados (G2) e tenotomizados e submetidos a EA (G3). Agulhas de acupuntura (AC) foram inseridas nos pontos E-36 e B-57 e uma corrente elétrica com onda farádica bipolar assimétrica na freqüência de 2 Hz e intensidade de 2-4 Volts foi aplicada nas agulhas por 20 minutos, 3 vezes por semana em dias alternados, em um total de 6 sessões. Análises bioquímicas foram feitas através da SDS-PAGE, dosagem de proteínas não colagênicas (PNCs), glicosaminoglicanos (GAGs) e hidroxiprolina. Análise da metaloproteinase-2 (MMP-2) foi realizada por zimografia. Para análise morfológica em microscopia de luz comum, os cortes foram corados com hematoxilina-eosina (HE) e azul de toluidina (AT). Para análise em microscopia de polarização os cortes foram corados com Ponceau SS e a birrefringência foi avaliada em termos de valor de média de cinza em pixels utilizando um analisador de imagem. Resultados: EA nos pontos utilizados não alterou a concentração de PNCs, GAGs ou a atividade enzimática da MMP-2 nos tendões transeccionados. Já a concentração de hidroxiprolina foi significativamente aumentada nestes tendões quando tratados com EA. Na análise morfológica nos cortes corados com HE e AT, aparentemente não houve alterações na composição nem na organização da MEC. No entanto, na análise da birrefringência houve uma maior reorganização das fibras de colágeno no grupo tratado com EA. Conclusão: Nossos resultados indicam que a EA pode oferecer benefícios terapêuticos para o tratamento de lesões tendíneas através do aumento do conteúdo do colágeno e da reorganização molecular de suas fibras<br>Abstract: Electroacupuncture (EA) has been used to treat a variety of inflammatory diseases and pain relief. Therefore, there are no reports in the literature about the effect of EA on the composition and organization of the extracellular matrix (ECM) of tendons in the healing process. Objective: To investigate by morphological and biochemical analysis, the effect of EA during the peak of synthesis of ECM components, 15 days after partial transection of the Achilles tendon of rats. Methods: Male Wistar rats with 60 days old were divided into three groups: no tenotomized (G1), tenotomized (G2) and tenotomized and submitted to EA (G3). Acupuncture (AC) needles were inserted in the E-36 and B-57 points and an electrical current with asymmetrical bipolar faradic wave at frequency of 2 Hz and intensity of 2-4 Volts was applied to the needles for 20 minutes, 3 times per week on alternate days, for a total of 6 sessions. Biochemical analyses were done by SDS-PAGE, dosage of non collagenous proteins (NCPs), glycosaminoglycans (GAGs) and hydroxyproline. Analysis of metalloproteinase-2 (MMP-2) was carried out by zymography. For morphological analyses, the sections were stained with hematoxilin-eosin (HE) and toluidine blue. For polarization microscopy analysis the sections were stained with Ponceau SS and birefringence was evaluated in terms of gray average values in pixels using an image analyzer. Results: EA at points used did not alter the concentration of NCPs, GAGs or the enzymatic activity of MMP-2 in transected tendons. However, the concentration of hydroxyproline was significantly increased when these tendons were treated with EA. In the morphological analysis, apparently there were no changes in the composition and organization of the ECM. However, analysis of the birefringence showed higher reorganization of collagen fibers in the group treated with EA. Conclusion: Our results indicate that EA may offer therapeutic benefits for treatment of tendon injuries by increasing the content of collagen and the molecular reorganization of its fibers<br>Mestrado<br>Anatomia<br>Mestre em Biologia Celular e Estrutural
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Guerra, Flavia Da Ré 1984. "Efeito de diferentes protocolos de laser de baixa potência sobre a cicatrização do tendão calcanear de ratos após transecção parcial = Effect of different protocols of low-power laser on the healing of rats Achilles tendon after partial transection." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317367.
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Orientador: Edson Rosa Pimentel<br>Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-23T11:50:11Z (GMT). No. of bitstreams: 1
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Previous issue date: 2013<br>Resumo: O tendão calcanear é o tendão mais acometido por ruptura, particularmente em atividades esportivas. O processo de cicatrização resulta em uma matriz extracelular (MEC) menos organizada o que reduz sua resistência à tensão e torna-o mais susceptível à recorrência de lesões. A terapia com o laser de baixa potência (LBP) tem se mostrado efetiva, porém existem resultados contraditórios com relação a seus protocolos. Propusemos-nos a avaliar os efeitos de diferentes terapias com o LBP em tendão calcanear parcialmente seccionado. Para tal foram utilizados ratos Wistar machos adultos, distribuídos em 7 grupos experimentais: G1- Tendão intacto; G2-Tendão seccionado; G3- lesão + LBP (4J/cm2-contínuo); G4- lesão + LBP (4J/cm2-20 Hz); G5- Tendão seccionado; G6- lesão + LBP (4J/cm2-contínuo); G7- lesão + LBP (4J/cm2-20 Hz até o 7º dia e 2 KHz do 8º ao 14º dia). G2, G3 e G4 foram eutanaziados no 8º dia após lesão, e G5, G6 e G7 no 15º dia. Foram realizadas as dosagens de proteínas não-colagênicas (PNC), glicosaminoglicanos (GAG) e hidroxiprolina (HOPro), além de eletroforese em gel de agarose, zimografia para MMP-2 e -9 e western blotting (WB) para colágeno I e III. O estudo estrutural foi feito por meio de lâminas coradas em hematoxilina-eosina (HE) e azul de toluidina (AT) além de análise e medidas de birrefringência por meio de microscopia de polarização. A análise funcional foi realizada por meio do Catwalk. Com relação à HOPro houve um decréscimo significativo em todos os grupos quando comparados ao G1, exceto G7. A dosagem de GAG revelou um aumento em todos os grupos exceto G5 e o gel de agarose mostrou um aumento no conteúdo de dermatan sulfado em todos os grupos transeccionados, sendo menos expressivo em G4 e G7. Nos cortes corados com AT os grupos transeccionados apresentaram maior metacromasia, em especial os grupos tratados. WB para colágeno I mostrou um aumento em G4 e G7. Quanto ao colágeno III G4 apresentou valores maiores quando comparado a G2. A zimografia para MMP-2 indicou maiores valores em G4 e G7. A MMP-9 aumentou em G3 e G4. A análise de birrefringência revelou acentuada desorganização em todos os grupos, com melhora significativa em G7. Os resultados do catwalk apontaram que, após a cirurgia os grupos que receberam o laser pulsado conseguiram apoiar melhor a pata quando comparado aos demais grupos. Nossos resultados mostram que o LBP contínuo e pulsado tem efeitos diferentes sobre o processo de reparo do tendão. O LBP pulsado atuou sobre o processo inflamatório possibilitando que o animal apoiasse melhor a pata ao caminhar e promoveu a síntese e organização do colágeno. Desta maneira acreditamos que este protocolo de tratamento pode ser adaptado para o uso em clínicas de reabilitação de maneira a acelerar o reparo e melhorar as características morfológicas, bioquímicas e funcionais deste tendão<br>Abstract: The Achilles tendon has a high incidence of rupture, particularly in sports activities. The healing process leads to a disorganized extracellular matrix (ECM) which reduces its tensile strength and lead to a high rate of injury recurrence. Low level laser therapy (LLLT) has been effective, but there are conflicting results regarding their protocols. Our purpose was to evaluate the effects of different therapies with LLLT in partially tenotomized Achilles tendon. Adult male Wistar rats were divided into 7 groups: G1 ? intact; G2 ? injured; G3 ? injured + LLL (4 J/cm2 continuous); G4 ? injured + LLL (4 J/cm2 ? 20 Hz); G5 ? injured; G6 ? injured + LLL (4 J/cm2 continuous); and G7 ? injured + LLL (4 J/cm2 ? 20 Hz until the 7th day and 2 kHz from 8?14 days). G2, G3 and G4 were euthanized 8 days after injury, and G5, G6 and G7 were euthanized on the 15th day. Quantification of non-collagenous protein (NCP), glycosaminoglycans (GAG) and hydroxyproline (HOPro) was performed, in addition to electrophoresis on agarose gel, zymography for MMP-2 and -9, western blotting (WB) for collagen types I and III. The structural analysis was done by hematoxylin-eosin (HE) and toluidine blue (TB) staines with in addition to birefringence measurements and analysis by polarization microscopy. Functional analysis was performed using the gait assessment of the animals in the Catwalk. Regarding HOPro there was a significant decrease in all groups when compared to the G1, except G7. The dosage of GAG showed an increase in all groups except G5 and agarose gel showed an increase in the content of dermatan sulfat in all transected groups, being less expressive in G4 and G7. In sections stained with TB the tenotomized groups showed metachromasia, particularly the treated groups. WB for collagen I showed an increase in G4 and G7. In G4 collagen III showed higher values when compared to G2. The zymography for MMPs-2 showed higher values for G4 and G7. MMP-9 increased in G3 and G4. Analysis of birefringence showed marked disorganization in all groups, with a significant improvement in G7. The catwalk results showed that after surgery, G4 had better results when compared to other groups. Our results show that the continuous and pulsed LLLT has different effects on the process of tendon repair. Pulsed laser acted on the inflammatory process improving the gait and promoting collagen synthesis and organization. Thus we believe that this treatment protocol can be adapted for use in rehabilitation clinics in order to accelerate the repair and enhance the morphological, biochemical and functional characteristics of the tendon<br>Doutorado<br>Anatomia<br>Doutora em Biologia Celular e Estrutural
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Pasternak, Björn. "Towards surgical use of matrix metalloproteinase biology." Doctoral thesis, Linköpings universitet, Ortopedi och idrottsmedicin, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-11489.
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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.
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Kuang, Guanming, and 邝冠明. "Preparation of a strontium enriched calcium phosphate cement and its use in accelerating the healing of a soft tissue tendon graft within the bone tunnel in a rabbit anterior cruciate ligament reconstruction model." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hdl.handle.net/10722/193043.
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Anterior cruciate ligament (ACL) rupture is a major clinical problem in sports medicine. The current mainstay of treatment is arthroscopic-assisted ACL reconstruction with a soft tissue tendon graft. However, the affected patients are required to abstain from any pivoting activity for at least six to nine months after the operation to protect the graft-host bone interface in order to allow the graft to heal.
In this study, a method to accelerate the graft healing within the bone tunnel is proposed by using a local application of an osteoconductive bone cement (Strontium enriched calcium phosphate cement, Sr-CPC) at the graft-host bone interface. It is postulated that Sr-CPC can induce earlier new bone formation in the gap between the graft and host bone tunnel and hence can result in an accelerated healing of the graft within the bone tunnel in ACL reconstruction.
Preparation of Sr-CPCs using the conventional setting method (a dissolution/precipitation process) leads to a delay in setting. This study adopted a new setting reaction, a chelate reaction, to manufacture a Sr-CPC system. The Sr-CPC system was fast-setting, injectable and cohesive, and it was suitable for use in minimally invasive orthopaedics surgeries (e.g. arthroscopic-assisted ACL reconstruction).
In order to investigate the biocompatibility and osteoconductivity of the Sr-CPC, in vitro cell experiments and an in vivo animal study were carried out. The in vitro experiments showed that the Sr-CPC was biocompatible with no local toxicity. In addition, a higher proliferation rate of osteoblastic-like MG-63 cells, accompanying higher alkaline phosphatase activity, was found in the Sr-CPC group. The in vivo study using a rat femur metaphyseal bone defect model showed evidence of earlier endochondral ossification which was noted at 2 weeks post operation. Moreover, a higher peri-cement bone formation rate, accompanied by a higher cement resorption rate, was found in the Sr-CPC group at 32 weeks after the operation compared with the convention calcium phosphate cement group.
To study the effect of the Sr-CPC on the graft healing within the bone tunnel, a one-stage bilateral ACL reconstruction using an Achilles tendon allograft was performed in 30 rabbits. One study (15 rabbits) was to investigate the effect of the Sr-CPC on the healing of a soft tissue tendon graft within the bone tunnel, and the other study (15 rabbits) was to study the difference between the Sr-CPC and the conventional CPC in the healing of a soft tissue tendon graft within the bone tunnel. The Sr-CPC treated graft showed an accelerated healing at all of the time points when compared with the non-treated graft; and at time points of 3 to 12 weeks when compared with the CPC treated graft.
In conclusion, a strontium enriched calcium phosphate cement, which is suitable for the arthroscopic use, was manufactured. It is biocompatible, osteoconductive and degradable. It accelerates the graft healing within the bone tunnels in a rabbit ACL reconstruction model using an Achilles tendon allograft when compared with both of the non-treated group and the conventional CPC-treated group.<br>published_or_final_version<br>Orthopaedics and Traumatology<br>Doctoral<br>Doctor of Philosophy
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Barbato, Kelly Biancardini Gomes. "Efeitos do uso de antiinflamatório e do exercício aeróbico sobre a regeneração tecidual e perfil biomecânico do tendão calcâneo de ratos após ruptura completa." Universidade do Estado do Rio de Janeiro, 2011. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=3845.
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Ruptura do tendão calcâneo é uma das lesões tendíneas mais frequentes. Embora a maioria dos trabalhos sugira que o exercício seja benéfico na cicatrização tendínea, não há consenso sobre o efeito do antiinflamatório neste contexto. Trabalhos experimentais tentam reproduzir lesão aguda deste tendão, em diferentes espécies animais. Neste estudo, descrevemos uma técnica de tenotomia completa do tendão calcâneo direito em ratos e, em seguida, avaliamos os efeitos do uso do antiinflamatório e do exercício aeróbico, isoladamente e em combinação, sobre a proliferação celular e o perfil biomecânico do tendão calcâneo, durante o processo de cicatrização após tenotomia. Estudo experimental com 156 ratos machos adultos, da raça Wistar, com idade média de 3 meses e peso médio de 300g. Após anestesia com tiopental e com auxílio da microscopia de luz, foi realizada incisão longitudinal posterior de cinco milímetros, em direção proximal, a partir da tuberosidade posterior do calcâneo da pata direita do rato. Foi feito corte transversal do tendão calcâneo, a sete milímetros da tuberosidade do calcâneo, com preservação do tendão plantar. Utilizamos as técnicas de Hematoxilina e Eosina, Picrosirius-red e Resorcina-fucsina de Weigert para avaliação da cicatrização tendínea e das fibras dos sistemas colágeno e elástico. Após a tenotomia, metade dos animais receberam tenoxicam intramuscular por 7 dias e no 8o dia iniciou-se protocolo de exercício em esteira na metade de cada grupo. Os ratos foram divididos aleatoriamente em 4 grupos de tratamento: A sem antiinflamatório E sem exercício (controle); B com antiinflamatório E com exercício; C sem antiinflamatório E com exercício; D com antiinflamatório E sem exercício. Os animais foram eutanasiados com 1, 2, 4 e 8 semanas após a tenotomia, para avaliação histológica pelo PCNA, e biomecânica através do teste de resistência à tração e da medida do ciclo locomotor. Foram realizados análise de variância, teste de Kruskal-Wallis e o método de Bonferroni, no programa R Project, versão 2.11.1. O tempo cirúrgico médio foi de 1 minuto e 24 segundos, sem complicações observadas até a 8a semana pós-operatória. Observamos proliferação celular e fibrilogênese com duas semanas, e diminuição da celularidade e das fibras elásticas na 8a semana, além de mudanças na organização estrutural do sistema colágeno. Encontramos pico da imunomarcação com PCNA na 2a semana em todos os grupos, exceto no grupo A, cujo pico aconteceu com 1 semana da tenotomia. Evidenciamos resistência à tração significativamente maior (p=0,02) nos ratos submetidos ao exercício, 8 semanas após ruptura. Nos grupos com antiinflamatório, observamos um ciclo locomotor mais estável durante todo o tempo avaliado. Consideramos a técnica cirúrgica experimental de tenotomia completa do tendão calcâneo, realizada com auxílio da microscopia de luz e preservação do tendão plantar, simples, rápida, com sinais de cicatrização tendínea normal e de fácil reprodução em ratos. O exercício aeróbico, iniciado precocemente após tenotomia completa do tendão calcâneo, é significativamente benéfico na sua recuperação biomecânica e o uso combinado com antiinflamatório confere maior estabilidade na marcha, o que pode proteger contra rerruptura tendínea em ratos<br>Achilles tendon rupture is one of the most frequent tendon injuries. Although most studies have shown the benefits of exercise on tendon regeneration, controversy still exists concerning non-steroidal antinflammatory drug (NSAID) effects in this context. Several experimental models have been used for the study of Achilles tendon injury. In this study, we describe the surgical technique of right Achilles tenotomy in rats and subsequently evaluate the effects of NSAID and aerobic exercise, in an isolated fashion and combined, on cell proliferation and biomechanical aspects of the Achilles tendon after tenotomy. Experimental study with 156 male Wistar rats with an average age of 3 months and with average weight of 300g. Surgical procedures were performed under light microscopy, after anesthesia with thiopental. A five millimeters posterior longitudinal incision was created, proximally directed, starting five millimeters proximal to the posterior calcaneal tuberosity. A complete tenotomy of the Achilles tendon was performed, seven millimeters away from the calcaneal tuberosity. The plantaris tendon was preserved. We used Hematoxilin and Eosin, Picrosirius-red and Weigerts Resorcin-fucsin to observe general tendon healing, especially regarding collagen and elastic fibers. After tenotomy, half of the rats received an intramuscular injection of tenoxican for 7 days and exercise was initiated on the 8th day for half the animals of each group. Rats were randomly divided into four treatment groups: A) no NSAID and no exercise; B) NSAID plus exercise; C) no NSAID, with exercise; D) NSAID and no exercise. Animals were sacrificed at 1, 2, 4 and 8 weeks after the tenotomy and cell proliferation was evaluated by immunohistochemistry for PCNA, biomechanical evaluation was performed with ultimate load and gait cycle analysis was also carried out. We used the test of analysis of variance, the Kruskal-Wallis test and also, Bonferroni method, in the R Project program 2.11.1. The mean operative time was one minute and 24 seconds, without complications observed until the 8th postoperative week. Histological studies showed cellular proliferation and fibrilogenesis at two weeks, with decreased amounts of cellularity and elastic fibers at the 8th week, besides changes in structural organization of collagen fibers. The highest intensity of PCNA immunostaining was found at 2 weeks in all groups except for group A (control) that had the highest intensity at 1 week. Animals submitted to exercise had significantly higher (P = 0.02) ultimate loads at 8 weeks after injury. The animals that received NSAID presented with a more stable gait cycle. The surgical technique described for complete Achilles tenotomy, under light microscopy and sparing the plantaris tendon, is simple and quick, shows signs of normal healing process, and it is easily reproducible in rats. Aerobic exercise, initiated early after a complete Achilles tendon tenotomy, was beneficial to the biomechanical aspects of the tendon during regeneration and the combined use of NSAID improved the gaits characteristics, which could be protective against reruptures
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Eliasson, Pernilla. "Response to mechanical loading in healing tendons." Doctoral thesis, Linköpings universitet, Ortopedi och idrottsmedicin, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-70774.
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Ruptured tendons heal faster if they are exposed to mechanical loading. Loading creates deformation of the extracellular matrix and cells, which give rise to intracellular signalling, increased gene expression and protein synthesis. The effects of loading have been extensively studied in vitro, and in intact tendons in vivo. However, the response to loading in healing tendons is less known. The general aim of this thesis was to understand more about the response to mechanical loading during tendon healing. The specific aims were to find out how short daily loading episodes could influence tendon healing, and to understand more about genes involved in tendon healing. The studies were performed using rat models. Unloading of healing tendons resulted in a weaker callus tissue. This could be reversed to some extent by short daily loading episodes. Loading induced more matrix production, making the tendons thicker and stronger, but there was no improvement in the material properties of the matrix. Lengthening is one potential adversity with early loading, during tendon healing in patients. This was also seen with continuous loading in the rat models. However, short loading episodes did not result in any lengthening, not even when loading was applied during the inflammatory phase of healing. It also appeared as loading once daily was enough to make healing tendons stronger, while loading twice daily with 8 hours interval did not give any additional effect. The strongest gene expression response to one loading episode was seen after 3 hours. The gene expression changes persisted 12 hours after the loading episode but had disappeared by 24 hours. Loading appeared to regulate genes involved in inflammation, wound healing and coagulation, angiogenesis, and production of reactive oxygen species. Inflammation-associated genes were regulated both by continuous loading and by one short loading episode. Inflammation is an important part of the healing response, but too much can be harmful. Loading might therefore have a role in fine-tuning the inflammatory response during healing. In conclusion, these studies show that short daily loading episodes during early tendon healing could potentially be beneficial for rehabilitation. Loading might have a role in regulating the inflammatory response during healing.
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Cumming, Benjamin Donald. "A mathematical model of wound healing and subsequent scarring." Queensland University of Technology, 2006. http://eprints.qut.edu.au/16300/.
Full textAbstract:
Wound healing is governed by a complex cascade of related processes, involving cells, extracellular matrix and cytokines. In adults this always results in a scar whilst embryonic wound healing is scarless and extensive research worldwide is aimed at reducing scarring in adults. A mathematical framework for problems in dermal wound healing is developed that incorporates models of the individual processes involved. Cells are modelled as discrete individuals. Cytokines and other biologically active factors are modelled as continua. A novel tensorial approach is taken to modelling the extracellular matrix. The numeric and computational challenges associated with combining models for the individual processes are identified and investigated. These include the development of data structures and numeric methods for the continuous and discrete species. Effective visualisation methods for the large amounts of data generated by the model are also discussed. The possibilities offered by high performance computing in mathematical biology are highlighted in this work. The final part of this thesis gives an example of a combined model of the inflammatory and proliferative phases of dermal wound healing using the new computational framework. Both quantitative and qualitative methods are used to analyse the information-rich data sets generated by the model, offering insight into the dynamic systems that can be modelled using the new approach.
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Dahlmann, Annegret Hella. "The effects of growth factors and mechanical tension on ocular fibroblasts in wound healing and scarring." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1444597/.
Full textAbstract:
Processes of wound healing or scarring cause many blinding eye conditions and can limit the success of surgical eye treatments. The mechanisms underlying matrix remodelling and contraction by connective tissue cells (fibroblasts) are not fully understood. Two main theories dominate the field: firstly, that fibroblasts in a wound begin to express alpha smooth muscle actin and transdifferentiate into myofibroblasts with enhanced contractile properties, and secondly that fibroblast migration might underly matrix condensation. The purpose of this work was to develop novel imaging techniques to investigate the mechanisms of tissue contraction and force generation using live cell and matrix imaging during fibroblast-mediated collagen gel contraction, and to determine the role played by growth factors and mechanical tension in that process. We have shown that fibroblasts from different parts of the eye display marked differences in macroscopic matrix contraction profiles, and that four factors determine the early matrix contraction profile: 1) cell size. 2) intrinsic cellular force. 3) growth factor-mediated actomyosin-based dynamic cell protrusive activity and 4) net pericellular matrix displacement. Intrinsic cellular force and dynamic activity appear to be independent unique characteristics of each cell type and might serve as predictors of matrix contraction. In addition, in corneal fibroblasts, we have shown that the recently identified PIXil rab5 RN I re-pathway mediates a specific type of cell protrusive activity leading to matrix contraction. Specific inhibitors of actomyosin- and rab5'RNTre-pathways are likely candidates to prevent corneal haze formation after surgery, trauma or inflammation, finally, we explored novel models of contraction involving real tissue by developing techniques to maintain and microscopically study ocular surface tissue ex vivo. We achieved successful concomitant live imaging of resident cells and extra-cellular matrix behaviour at high resolution in both conjunctival and corneal stroma by combining optimized strategies for tissue maintenance, fluorescent cell labeling, and confocal laser and/or two-photon microscopy. In summary, this thesis presents novel pathways of matrix contraction and imaging techniques to study these events in vitro and ex vivo.
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Petersson, Ludvig. "The Roles of Growth Factor Interactions and Mechanical Tension in Angiogenesis." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-113238.
Full textAbstract:
Angiogenesis, the formation of new blood vessels from preexisting ones through creation of new vessel branch points by sprouting or vessel splitting, is an important part of tissue growth in both physiological processes like wound healing and pathological conditions such as cancer. Growth factors like VEGF-A, FGF-2 and PDGF-BB are involved in both types of angiogenesis. Screening for genes regulated by VEGF-A stimulation in endothelial cells revealed up regulation of the endothelial cell specific glycoprotein endocan. Endocan itself did not stimulate angiogenesis. VEGF was a specific inducer since FGF-2, PDGF-BB, HGF and EGF did not alter expression. The signaling molecule PI3K was a negative regulator of endocan expression. Endocan was expressed in tumor cells and vessels, suggesting that although endocan did not directly regulate angiogenesis it can serve as a marker for angiogenic tumors. In two models of wound healing angiogenesis, the chick extra-embryonal CAM assay and the mouse cornea assay, we observed that blood vessels grew into avascular areas as functional mural cell covered loops by elongation of preexisting vessels. Loop formation was simultaneous with contraction of the avascular matrix mediated by proto/myofibroblasts. Reducing the contractibility of the stroma reduced vessel ingrowth, showing that contraction was necessary for mediating and directing growth of the vascular loops. These findings suggest a model for biomechanical regulation of vascularization that is complementary to sprouting angiogenesis which is guided by gradients of growth factors. In defining the role of growth factors, in the CAM assay, we found that FGF-2 and PDGF-BB induced vessel ingrowth, while VEGF-A, EGF and HGF did not. TGF-beta reduced the effect of FGF-2. By use of specific receptor kinase inhibitors we found an absolute requirement VEGF- and PDGF-receptor activity for vascularization while FGF- and TGF-beta-receptor function was dispensable. This suggests that functional VEGF- and PDGF-receptors are needed for vessel elongation.