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Sample records for tendon collagen synthesis

  1. Tendon collagen synthesis declines with immobilization in elderly humans

    DEFF Research Database (Denmark)

    Dideriksen, Kasper; Boesen, Anders P; Reitelseder, Søren

    2017-01-01

    -80 yr) were randomly assigned to NSAIDs (ibuprofen 1,200 mg/day; Ibu) or placebo (Plc). One lower limb was immobilized in a cast for 2 wk and retrained for 6 wk. Tendon collagen protein synthesis, mechanical properties, size, expression of genes related to collagen turnover and remodeling, and signal...... intensity (from magnetic resonance imaging) were investigated. Tendon collagen synthesis decreased (P ... immobilization in both groups, whereas scleraxis mRNA decreased with inactivity in the Plc group only (P collagen protein synthesis decreased after 2 wk of immobilization, whereas tendon stiffness and modulus were only marginally reduced, and NSAIDs had no influence upon this...

  2. Effect of estrogen on tendon collagen synthesis, tendon structural characteristics, and biomechanical properties in postmenopausal women

    DEFF Research Database (Denmark)

    Hansen, M.; Kongsgaard, M; Holm, Lars

    2009-01-01

    therapy (ERT, n = 10) were studied at rest and in response to one-legged resistance exercise. Synthesis of tendon collagen was determined by stable isotope incorporation [fractional synthesis rate (FSR)] and microdialysis technique (NH(2)-terminal propeptide of type I collagen synthesis). Tendon area...

  3. GH receptor blocker administration and muscle-tendon collagen synthesis in humans

    DEFF Research Database (Denmark)

    Nielsen, Rie Harboe; Doessing, Simon; Goto, Kazushige

    2011-01-01

    The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans.......The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans....

  4. GH receptor blocker administration and muscle-tendon collagen synthesis in humans

    DEFF Research Database (Denmark)

    Nielsen, Rie H; Doessing, Simon; Goto, K.

    2011-01-01

    Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing......, but the effect of local IGF-I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 ± 1 years (mean ± SEM), BMI 27 ± 1......] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection...

  5. Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis

    DEFF Research Database (Denmark)

    Doessing, Simon; Heinemeier, Katja; Holm, Lars

    2010-01-01

    matrix collagen synthesis in skeletal muscle and tendon, but without any effect upon myofibrillar protein synthesis. The results suggest that GH is more important in strengthening the matrix tissue than for muscle cell hypertrophy in adult human musculotendinous tissue.......In skeletal muscle and tendon the extracellular matrix confers important tensile properties and is crucially important for tissue regeneration after injury. Musculoskeletal tissue adaptation is influenced by mechanical loading, which modulates the availability of growth factors, including growth...... young individuals. rhGH administration caused an increase in serum GH, serum IGF-I, and IGF-I mRNA expression in tendon and muscle. Tendon collagen I mRNA expression and tendon collagen protein synthesis increased by 3.9-fold and 1.3-fold, respectively (P muscle collagen I m...

  6. Local administration of insulin-like growth factor-I (IGF-I) stimulates tendon collagen synthesis in humans

    DEFF Research Database (Denmark)

    Hansen, M; Boesen, A; Holm, L

    2013-01-01

    Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing...

  7. From mechanical loading to collagen synthesis, structural changes and function in human tendon

    DEFF Research Database (Denmark)

    Kjær, Michael; Langberg, Henning; Heinemeier, Katja

    2009-01-01

    a similar response whether the tendon was stimulated by concentric, isometric or eccentric muscle contraction, suggesting that strain rather that stress/torque determines the collagen-synthesis stimulating response seen with exercise. The adaptation time to chronic loading is longer in tendon tissue...... of TGF-beta, PGE2, IGF-I plus its binding proteins and interleukin-6 takes place after exercise. The increase in IGF-I expression in tendon includes the isoform that has so far been thought only to exist in skeletal muscle (mechano growth factor). The increase in IGF-I and procollagen expression showed...... compared with contractile elements of skeletal muscle or the heart, and only with very prolonged loading are significant changes in gross dimensions of the tendon observed, suggesting that habitual loading is associated with a robust change in the size and mechanical properties of human tendons...

  8. Insulin-like growth factor I enhances collagen synthesis in engineered human tendon tissue

    DEFF Research Database (Denmark)

    Herchenhan, Andreas; Bayer, Monika L.; Eliasson, Pernilla

    2015-01-01

    investigated the influence of insulin-like growth factor I (IGF-I) on tendon construct formation in 3D cell culture. DESIGN: Tendon constructs were grown in 0.5 or 10% FBS with or without IGF-I (250 mg/ml) supplementation. Collagen content (fluorometric), mRNA levels (PCR) and fibril diameter (transmission...... of fibril diameter (day 14), collagen content (at days 21 and 28) and mRNA expression for collagen, tenomodulin and scleraxis. CONCLUSION: IGF-I supplementation promotes early onset of tensile load induced collagen formation and tendon structural arrangement, whereas the FBS concentration routinely used......OBJECTIVE: Isolated human tendon cells form 3D tendon constructs that demonstrate collagen fibrillogenesis and feature structural similarities to tendon when cultured under tensile load. The exact role of circulating growth factors for collagen formation in tendon is sparsely examined. We...

  9. Ethinyl oestradiol administration in women suppresses synthesis of collagen in tendon in response to exercise

    DEFF Research Database (Denmark)

    Hansen, Mette; Koskinen, Satu O; Petersen, Susanne G

    2008-01-01

    -OC 24 h post-exercise is consistent with the hypothesis that oestradiol inhibits exercise-induced collagen synthesis in human tendon. The mechanism behind this is either a direct effect of oestradiol, or an indirect effect via a reduction in levels of free IGF-I. However, the data did not indicate any...... for 60 min at 67% of maximum power by healthy, young oral contraceptive (OC) users when circulating synthetic (ethinyl) oestradiol was high (n = 11, HE-OC) and compared to similar women who had never used OCs when circulating endogenous oestrogen was low (n = 12, LE-NOC). Interstitial fluid was collected...

  10. Achilles tendon rupture healing is enhanced by intermittent pneumatic compression upregulating collagen type I synthesis.

    Science.gov (United States)

    Abdul Alim, Md; Domeij-Arverud, Erica; Nilsson, Gunnar; Edman, Gunnar; Ackermann, Paul W

    2017-07-01

    Adjuvant intermittent pneumatic compression (IPC) during leg immobilization following Achilles tendon rupture (ATR) has been shown to reduce the risk of deep venous thrombosis. The purpose of this study was to investigate whether IPC can also promote tendon healing. One hundred and fifty patients with surgical repair of acute ATR were post-operatively leg immobilized and prospectively randomized. Patients were allocated for 2 weeks of either adjuvant IPC treatment (n = 74) or treatment-as-usual (n = 74) in a plaster cast without IPC. The IPC group received 6 h daily bilateral calf IPC applied under an orthosis on the injured side. At 2 weeks post-operatively, tendon healing was assessed using microdialysis followed by enzymatic quantification of tendon callus production, procollagen type I (PINP) and type III (PIIINP) N-terminal propeptide, and total protein content. 14 IPC and 19 cast patients (control group) consented to undergo microdialysis. During weeks 3-6, all subjects were leg-immobilized in an orthosis without IPC. At 3 and 12 months, patient-reported outcome was assessed using reliable questionnaires (ATRS and EQ-5D). At 12 months, functional outcome was measured using the validated heel-rise test. At 2 weeks post-rupture, the IPC-treated patients exhibited 69% higher levels of PINP in the ruptured Achilles tendon (AT) compared to the control group (p = 0.001). Interestingly, the IPC-treated contralateral, intact AT also demonstrated 49% higher concentrations of PINP compared to the non-treated intact AT of the plaster cast group (p = 0.002). There were no adverse events observed associated with IPC. At 3 and 12 months, no significant (n.s.) differences between the two treatments were observed using patient-reported and functional outcome measures. Adjuvant IPC during limb immobilization in patients with ATR seems to effectively enhance the early healing response by upregulation of collagen type I synthesis, without any adverse effects

  11. Radiofrequency preserves histoarchitecture and enhances collagen synthesis in experimental tendon injury.

    Science.gov (United States)

    Akamatsu, Flavia Emi; Saleh, Samir Omar; Hojaij, Flávio; Martinez, Carlos Augusto Real; Andrade, Mauro; Teodoro, Walcy Rosolia; Jacomo, Alfredo Luiz

    2016-05-01

    We investigated the action of radiofrequency (RF) on the healing process after inducing experimental lesions of the Achilles tendon in rats. Wistar rats were surgically subjected to bilateral partial transverse sectioning of the Achilles tendon. The right tendon was treated with radiofrequency (RFT), whereas the left tendon served as a control (CT). On the third postoperative day, the rats were divided into three experimental groups consisting of ten rats each, which were treated with monopolar radiofrequency (Tonederm™) until they were sacrificed on the 7th, 14th or 28th days. The histological specimens were studied for inflammatory cell content, collagen types I and III, immunostaining and morphometry. Total collagen were biochemically analyzed and to evalute fibroblast and myofibroblast proliferation by vimentin and α-actin smooth muscle immunohistochemistry methods. Statistical analysis was performed using the Student's t-test, the sign test and the Kruskal-Wallis test to compare tendons treated with radiofrequency with the non-treated tendons (α=5%; α=10%). Larger amounts of collagen I with hydroxyproline content and myofibroblast cells were clearly evident within 7 days (ptendon healing. Clinical studies may include RF among the therapeutic tools in tendinous lesion management.

  12. Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women

    DEFF Research Database (Denmark)

    Hansen, M; Miller, B F; Holm, Lars

    2009-01-01

    , body composition, and exercise-training status were included. The two groups were either habitual users of oral contraceptives exposed to a high concentration of synthetic estradiol and progestogens (OC, n = 11), or non-OC-users tested in the follicular phase of the menstrual cycle characterized by low...... concentrations of estradiol and progesterone (control, n = 12). Subjects performed 1 h of one-legged kicking exercise. The next day collagen fractional synthesis rates (FSR) in tendon and muscle connective tissue were measured after a flooding dose of [(13)C]proline followed by biopsies from the patellar tendon...

  13. Synthesis, development, characterization and effectiveness of bovine pure platelet gel-collagen-polydioxanone bioactive graft on tendon healing

    Science.gov (United States)

    Moshiri, Ali; Oryan, Ahmad; Meimandi-Parizi, Abdolhamid

    2015-01-01

    Bovine platelet gel (BPG) is an accessible and cost-effective source of growth factors which may have a value in tendon regenerative medicine. We produced a collagen implant (CI) as a tendon proper, covered it with polydioxanone (PDS) sheath to simulate paratenon and finally embedded the BPG as an active source of growth factor within the bioimplant to test whether BPG would be able to accelerate and enhance tendon regeneration and repair. After in vitro characterization of the bioactive grafts, the grafts were implanted in rabbit large tendon defect model. Untreated tendons and tendons treated with either CI or CI-PDS were served as controls for the CI-PDS-BPG. The animals were investigated clinically, ultrasonographically and haematologically for 120 days. After euthanasia, dry matter content, water uptake and delivery characteristics and also gross morphological, histopathological and scanning electron microscopic features of the healing tendons were assessed. In vitro, the activated platelets in the scaffold, released their growth factors significantly more than the controls. BPG also increased cell viability, and enhanced cellular differentiation, maturation and proliferation inside the CI-PDS compared with the controls. In vivo, the BPG modulated inflammation, increased quality and rate of fibroplasia and produced a remodelled tendon that had significantly higher collagen content and superior collagen fibril and fibre differentiation than controls. Treatment also significantly improved tendon water uptake and delivery characteristics, animals’ serum PDGF level, CI-PDS biocompatibility and biodegradability and reduced peritendinous adhesions, muscle fibrosis and atrophy. BPG was effective on tendon healing and CI-PDS-BPG may be a valuable bioscaffold in tendon reconstructive surgery. PMID:25702535

  14. Collagen Structure of Tendon Relates to Function

    Directory of Open Access Journals (Sweden)

    Marco Franchi

    2007-01-01

    Full Text Available A tendon is a tough band of fibrous connective tissue that connects muscle to bone, designed to transmit forces and withstand tension during muscle contraction. Tendon may be surrounded by different structures: 1 fibrous sheaths or retinaculae; 2 reflection pulleys; 3 synovial sheaths; 4 peritendon sheaths; 5 tendon bursae. Tendons contain a few cells, mostly represented by tenoblasts along with endothelial cells and some chondrocytes; b proteoglycans (PGs, mainly decorin and hyaluronan, and c collagen, mostly type I. Tendon is a good example of a high ordered extracellular matrix in which collagen molecules assemble into filamentous collagen fibrils (formed by microfibrils which aggregate to form collagen fibers, the main structural components. It represents a multihierarchical structure as it contains collagen molecules arranged in fibrils then grouped in fibril bundles, fascicles and fiber bundles that are almost parallel to the long axis of the tendon, named as primary, secondary and tertiary bundles. Collagen fibrils in tendons show prevalently large diameter, a D-period of about 67 nm and appear built of collagen molecules lying at a slight angle (< 5°. Under polarized light microscopy the collagen fiber bundles appear crimped with alternative dark and light transverse bands. In recent studies tendon crimps observed via SEM and TEM show that the single collagen fibrils suddenly changing their direction contain knots. These knots of collagen fibrils inside each tendon crimp have been termed “fibrillar crimps”, and even if they show different aspects they all may fulfil the same functional role. As integral component of musculoskeletal system, the tendon acts to transmit muscle forces to the skeletal system. There is no complete understanding of the mechanisms in transmitting/absorbing tensional forces within the tendon; however it seems likely that a flattening of tendon crimps may occur at a first stage of tendon stretching

  15. Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise

    DEFF Research Database (Denmark)

    Miller, Benjamin F; Olesen, Jens L; Hansen, Mette

    2005-01-01

    in target proteins by gas chromatography-mass spectrometry. Patellar tendon and quadriceps biopsies were taken in exercised and rested legs at 6, 24, 42 or 48 and 72 h after exercise. The fractional synthetic rates of all proteins were elevated at 6 h and rose rapidly to peak at 24 h post exercise (tendon...... in human tendon and muscle. The similar time course of changes of protein synthetic rates in different cell types supports the idea of coordinated musculotendinous adaptation....

  16. No donor age effect of human serum on collagen synthesis signaling and cell proliferation of human tendon fibroblasts

    DEFF Research Database (Denmark)

    Bayer, Monika L; Schjerling, Peter; Biskup, Edyta

    2012-01-01

    The aging process of tendon tissue is associated with decreased collagen content and increased risk for injuries. An essential factor in tendon physiology is transforming growth factor-ß1 (TGF-ß1), which is presumed to be reduced systemically with advanced age. The aim of this study was to invest......The aging process of tendon tissue is associated with decreased collagen content and increased risk for injuries. An essential factor in tendon physiology is transforming growth factor-ß1 (TGF-ß1), which is presumed to be reduced systemically with advanced age. The aim of this study...... and elderly donors, and we found no difference in collagen expression when cells were subjected to human serum from elderly versus young donors. In addition, tendon cell proliferation was similar when culture medium was supplemented with serum of different donor age. These findings suggest that factors...... such as the cell intrinsic capacity or the tissue-specific environment rather than systemic circulating factors are important for functional capacity throughout life in human tendon cells....

  17. Effect of anti-inflammatory medication on the running-induced rise in patella tendon collagen synthesis in humans

    DEFF Research Database (Denmark)

    Christensen, Britt; Dandanell, Sune; Kjaer, Michael

    2011-01-01

    NSAIDs are widely used in the treatment of inflammatory diseases as well as of tendon diseases associated with pain in sports and labor. However, the effect of NSAID intake, and thus blockade of PGE(2) production, on the tendon tissue adaptation is unknown. The purpose of the present study...... was to elucidate the possible effects of NSAID intake on healthy tendon collagen turnover in relation to a strenuous bout of endurance exercise. Fifteen healthy young men were randomly assigned into two experimental groups, with one group receiving indomethacin (oral 2 × 100 mg Confortid daily for 7 days; NSAID; n...

  18. The effect of acute exercise on collagen turnover in human tendons

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Pingel, Jessica; Boesen, Mikael

    2013-01-01

    Mechanical loading of human tendon stimulates collagen synthesis, but the relationship between acute loading responses and training status of the tendon is not clear. We tested the effect of prolonged load deprivation on the acute loading-induced collagen turnover in human tendons, by applying...... the same absolute load to a relative untrained Achilles tendon (2-week immobilization period prior to acute loading) and a habitually loaded contra-lateral Achilles tendon, respectively, within the same individuals. Eight untrained, healthy males had one lower limb totally immobilized for 2 weeks, whereas...... the contra-lateral leg was used habitually. Following the procedure both Achilles tendons and calf muscles were loaded with the same absolute load during a 1-h treadmill run. Tissue collagen turnover was measured by microdialysis performed post-immobilization but pre-exercise around both Achilles tendons...

  19. Metabolic activity and collagen turnover in human tendon in response to physical activity

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, H; Miller, B F

    2005-01-01

    Connective tissue of the human tendon plays an important role in force transmission. The extracellular matrix turnover of tendon is influenced by physical activity. Blood flow, oxygen demand, and the level of collagen synthesis and matrix metalloproteinases increase with mechanical loading. Gene ...

  20. Collagen synthesis in human musculoskeletal tissues and skin

    DEFF Research Database (Denmark)

    Babraj, J A; Cuthbertson, D J R; Smith, K

    2005-01-01

    We have developed a direct method for the measurement of human musculoskeletal collagen synthesis on the basis of the incorporation of stable isotope-labeled proline or leucine into protein and have used it to measure the rate of synthesis of collagen in tendon, ligament, muscle, and skin....... In postabsorptive, healthy young men (28 +/- 6 yr) synthetic rates for tendon, ligament, muscle, and skin collagen were 0.046 +/- 0.005, 0.040 +/- 0.006, 0.016 +/- 0.002, and 0.037 +/- 0.003%/h, respectively (means +/- SD). In postabsorptive, healthy elderly men (70 +/- 6 yr) the rate of skeletal muscle collagen...... synthesis is greater than in the young (0.023 +/- 0.002%/h, P collagen are similar to those of mixed skeletal muscle protein in the postabsorptive state, whereas the rate for muscle collagen synthesis is much lower in both young and elderly men...

  1. From Tendon Injury to Collagen-based Tendon Regeneration: Overview and Recent Advances.

    Science.gov (United States)

    Rieu, Clement; Picaut, Lise; Mosser, Gervaise; Trichet, Lea

    2017-01-01

    Tendon injury is a clinical, societal and economical issue. Moreover, tendon repair represents an important clinical challenge, partly due to the mechanical constraints that occur at the junctions with muscle and bone. Several strategies have been developed for tendon repair. In this review, we first assess the importance of tendon injuries from different sites and their causes. After a short overview of tendon three-dimensional organization, the complexity of the perfect repair quest is presented ranging from current clinical procedures to new engineering scaffolds. We then sum up tendon engineering requirements and focus on new collagen-based scaffolds, which raise promising prospects to mimic and repair tendon. In particular, we survey quantitatively a large panel of techniques to produce these scaffolds, detailing their principle and recent improvements. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Role of moderate exercising on Achilles tendon collagen crimping patterns and proteoglycans.

    Science.gov (United States)

    Franchi, Marco; Torricelli, Paola; Giavaresi, Gianluca; Fini, Milena

    2013-01-01

    In this study, the morphological and morphometric changes in the collagen crimping pattern of Achilles tendon and metabolism/expression of tenocytes explanted from tendons of running (RUN) and sedentary (SED) rats were investigated to assess the effects of 12 weeks moderate running exercise. The number, the top angle width and the base length of each crimp in three different regions (proximal, central and distal) of RUN and SED tendons were measured with a polarized light microscope. The most significant morphometric differences in the crimps were detectable in the central region of the RUN tendons. In this region, crimps were fewer, larger and more flattened than those of other regions as a consequence of a functional adaptation of extracellular matrix to running, in order to increase tendon stiffness and force transmission efficiency. Conversely, the top angle width of the crimps reduced in proximal and distal regions of the RUN tendons, suggesting that these crimps might act as more reactive mechanical springs, able to store and improve the release of the stored strain energy in most loaded regions. Tenocytes explanted from Achilles tendons of both RUN and SED groups were cultured. Running influenced tenocytes which showed a significant increase in collagen type-I synthesis and proteoglycans production, suggesting enhancement of the loading transmission efficiency and facilitate inter-fibril and inter-fiber sliding.

  3. Osmotic pressure induced tensile forces in tendon collagen

    Science.gov (United States)

    Masic, Admir; Bertinetti, Luca; Schuetz, Roman; Chang, Shu-Wei; Metzger, Till Hartmut; Buehler, Markus J.; Fratzl, Peter

    2015-01-01

    Water is an important component of collagen in tendons, but its role for the function of this load-carrying protein structure is poorly understood. Here we use a combination of multi-scale experimentation and computation to show that water is an integral part of the collagen molecule, which changes conformation upon water removal. The consequence is a shortening of the molecule that translates into tensile stresses in the range of several to almost 100 MPa, largely surpassing those of about 0.3 MPa generated by contractile muscles. Although a complete drying of collagen would be relevant for technical applications, such as the fabrication of leather or parchment, stresses comparable to muscle contraction already occur at small osmotic pressures common in biological environments. We suggest, therefore, that water-generated tensile stresses may play a role in living collagen-based materials such as tendon or bone.

  4. Evidence of structurally continuous collagen fibrils in tendon

    DEFF Research Database (Denmark)

    Svensson, Rene B; Herchenhan, Andreas; Starborg, Tobias

    2017-01-01

    in this structure-function relationship is the collagen fibril length. During embryogenesis short fibrils are produced but they grow rapidly with maturation. There is some controversy regarding fibril length in adult tendon, with mechanical data generally supporting discontinuity while structural investigations...... favor continuity. This study initially set out to trace the full length of individual fibrils in adult human tendons, using serial block face-scanning electron microscopy. But even with this advanced technique the required length could not be covered. Instead a statistical approach was used on a large...... fibrils was confirmed. In light of these results, possible mechanisms that could reconcile the opposing findings on fibril continuity are discussed. STATEMENT OF SIGNIFICANCE: Connective tissues hold all parts of the body together and are mostly constructed from thin threads of the protein collagen...

  5. Arrabidaea chica extract improves gait recovery and changes collagen content during healing of the Achilles tendon.

    Science.gov (United States)

    Aro, A A; Simões, G F; Esquisatto, M A M; Foglio, M A; Carvalho, J E; Oliveira, A L R; Gomes, L; Pimentel, E R

    2013-07-01

    treated with the plant extract 7 days after injury (type I: 103.9±15.9; type III: 206.3±8.1) compared to the saline-treated groups (type I: 165.2±31.1; type III: 338.6±48.8). The plant extract stimulated the synthesis of MMP-2 on the 21st day after the lesion and decreased the amount of latent and active isoforms of MMP-9 on the 14th day. Analysis by the catwalk system (max contact intensity) showed that the A. chica extract improved the gait of rats on the 7th day of the healing process when compared to the saline group. The use of A. chica extract during the healing process of the tendon leads to an increase in collagen content and improved gait recovery. Further studies will be performed to analyze the effect of this plant extract on the organization of the collagen bundles of tendons after lesions and to study its probable anti-inflammatory effect. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. New approaches and recent results concerning human-tissue collagen synthesis.

    Science.gov (United States)

    Smith, Ken; Rennie, Michael J

    2007-09-01

    Knowledge of the physiological regulation of human-tissue collagen metabolism in vivo is poor, due to the lack of appropriately robust methods. Recent application of stable isotope tracer techniques to measure human collagen synthesis has provided some insights into the role of nutrition and exercise on collagen turnover in the extracellular matrix of the musculoskeletal system. Collagen turnover in the musculoskeletal system is faster than previously thought. Bone collagen synthesis is increased by feeding, whereas both muscle collagen and tendon are unresponsive. Exercise stimulates collagen synthesis in both muscle and tendon in an apparently coordinated manner. There are also sex differences and normal aging is associated with increased muscle collagen synthesis and reductions in bone collagen synthesis, particularly in mature bone collagen. Collagen turnover appears to be faster than previously thought and is regulated by feeding and exercise, in a tissue-specific manner. Further application of these approaches, coupled with measures of gene and protein expression, to measure the acute regulation of collagen, will lead to a better understanding of the physiology and pathophysiology of human collagen turnover. This is particularly important for developing new therapies to improve bone health and minimize tissue fibrosis.

  7. Cross-linking in collagen by nonenzymatic glycation increases the matrix stiffness in rabbit achilles tendon.

    Science.gov (United States)

    Reddy, G Kesava

    2004-01-01

    Nonenzymatic glycation of connective tissue matrix proteins is a major contributor to the pathology of diabetes and aging. Previously the author and colleagues have shown that nonenzymatic glycation significantly enhances the matrix stability in the Achilles tendon (Reddy et al., 2002, Arch. Biochem. Biophys., 399, 174-180). The present study was designed to gain further insight into glycation-induced collagen cross-linking and its relationship to matrix stiffness in the rabbit Achilles tendon. The glycation process was initiated by incubating the Achilles tendons (n = 6) in phosphate-buffered saline containing ribose, whereas control tendons (n = 6) were incubated in phosphate-buffered saline without ribose. Eight weeks following glycation, the biomechanical attributes as well as the degree of collagen cross-linking were determined to examine the potential associations between matrix stiffness and molecular properties of collagen. Compared to nonglycated tendons, the glycated tendons showed increased maximum load, stress, strain, Young's modulus of elasticity, and toughness indicating that glycation increases the matrix stiffness in the tendons. Glycation of tendons resulted in a considerable decrease in soluble collagen content and a significant increase in insoluble collagen and pentosidine. Analysis of potential associations between the matrix stiffness and degree of collagen cross-linking showed that both insoluble collagen and pentosidine exhibited a significant positive correlation with the maximum load, stress, and strain, Young's modulus of elasticity, and toughness (r values ranging from.61 to.94) in the Achilles tendons. However, the soluble collagen content present in neutral salt buffer, acetate buffer, and acetate buffer containing pepsin showed an inverse relation with the various biomechanical attributes tested (r values ranging from.22 to.84) in the Achilles tendons. The results of the study demonstrate that glycation-induced collagen cross

  8. The role of the non-collagenous matrix in tendon function

    Science.gov (United States)

    Thorpe, Chavaunne T; Birch, Helen L; Clegg, Peter D; Screen, Hazel RC

    2013-01-01

    Tendon consists of highly ordered type I collagen molecules that are grouped together to form subunits of increasing diameter. At each hierarchical level, the type I collagen is interspersed with a predominantly non-collagenous matrix (NCM) (Connect. Tissue Res., 6, 1978, 11). Whilst many studies have investigated the structure, organization and function of the collagenous matrix within tendon, relatively few have studied the non-collagenous components. However, there is a growing body of research suggesting the NCM plays an important role within tendon; adaptations to this matrix may confer the specific properties required by tendons with different functions. Furthermore, age-related alterations to non-collagenous proteins have been identified, which may affect tendon resistance to injury. This review focuses on the NCM within the tensional region of developing and mature tendon, discussing the current knowledge and identifying areas that require further study to fully understand structure–function relationships within tendon. This information will aid in the development of appropriate techniques for tendon injury prevention and treatment. PMID:23718692

  9. Role of TGF-beta1 in relation to exercise-induced type I collagen synthesis in human tendinous tissue

    DEFF Research Database (Denmark)

    Heinemeier, Katja; Langberg, Henning; Olesen, Jens L

    2003-01-01

    Mechanical loading of tissue is known to influence local collagen synthesis, and microdialysis studies indicate that mechanical loading of human tendon during exercise elevates tendinous type I collagen production. Transforming growth factor-beta1 (TGF-beta1), a potent stimulator of type I collagen...

  10. Orientation analysis of collagen fibers in healing tendon by using second-harmonic-generation microscopy

    Science.gov (United States)

    Hase, E.; Minamikawa, T.; Sato, K.; Yonekura, D.; Takahashi, M.; Yasui, T.

    2017-02-01

    Tendon rupture is a trauma that is difficult to fully recover from. Therefore, non-destructive and non-invasive evaluation method for the tendon healing is strongly required. In this study, we performed the orientation analysis of collagen fiber in healing tendon by two-dimensional Fourier transform (2D-FT) of SHG image. The extracted 2D-FT power spectra imply the correlation with the degree of the tendon healing. These results indicate that SHG microscopy has a unique potential as a non-destructive and non-invasive indicator of tendon healing.

  11. Micromechanical properties and collagen composition of ruptured human achilles tendon

    DEFF Research Database (Denmark)

    Hansen, Philip; Kovanen, Vuokko; Hölmich, Per

    2013-01-01

    The Achilles tendon is one of the strongest tendons in the human body, and yet it frequently ruptures, which is a substantial clinical problem. However, the cause of ruptures remains elusive.......The Achilles tendon is one of the strongest tendons in the human body, and yet it frequently ruptures, which is a substantial clinical problem. However, the cause of ruptures remains elusive....

  12. Effects of long-term immobilization and recovery on human triceps surae and collagen turnover in the Achilles tendon in patients with healing ankle fracture

    DEFF Research Database (Denmark)

    Christensen, Britt; Dyrberg, Eva; Aagaard, Per

    2008-01-01

    The aim of the present study was to analyze how human tendon connective tissue responds to an approximately 7-wk period of immobilization and a remobilization period of a similar length, in patients with unilateral ankle fracture, which is currently unknown. Calf muscle cross-sectional area (CSA...... or remobilization. Local collagen turnover was measured as the peritendinous concentrations of NH2-terminal propeptide of type I collagen (PINP) and COOH-terminal telopeptide region of type I collagen (ICTP), markers thought to be indexes of type I collagen synthesis and degradation, respectively. Both markers were...

  13. Biomechanical evaluation of acellular collagen matrix augmented Achilles tendon repair in sheep.

    Science.gov (United States)

    Song, Lin; Olsen, Raymond E; Spalazzi, Jeffrey P; Davisson, Twana

    2010-01-01

    The rate of rerupture of repaired Achilles tendon in young and athletic populations remains high despite improvement in surgical techniques, suture design, and postsurgical management. Acellular biological matrices can be used to enhance the immediate strength of repaired tendons and to serve as scaffolds for cell in-growth and constructive tissue remodeling. A number of commercially available matrices have been used clinically, albeit with varying degrees of success and failure. The disparity is likely attributable to the different physical and biochemical properties of individual matrices. In this study, we investigated the biomechanical characteristics of 2 different acellular collagen matrices, namely TissueMend and GraftJacket, using a sheep Achilles tendon repair model. Static and cyclic creep, cyclic and linear construct stiffness, maximum load to failure, and displacement at maximum load were determined at time zero. We found that the maximum load to failure, displacement, and ultimate failure mode were similar between tendons augmented with either acellular collagen matrix; however, TissueMend augmentation yielded lower creep and smaller construct elongation than did GraftJacket. The results indicated that the strength of TissueMend-augmented tendons and GraftJacket-augmented tendons was not statistically significantly different, although tendons augmented with TissueMend displayed greater stiffness, which may be clinically advantageous in the restoration of ruptured tendons. Copyright 2010 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Genipin crosslinking elevates the strength of electrochemically aligned collagen to the level of tendons.

    Science.gov (United States)

    Alfredo Uquillas, Jorge; Kishore, Vipuil; Akkus, Ozan

    2012-11-01

    Collagen-based tissue mimics are important in clinical research because collagen is the main structural element in tendons. The current study aimed to improve the mechanical strength of Electronically Aligned Collagen (ELAC) threads by optimizing several crosslinking parameters. The results indicated that elevating the concentration of genipin to 2% and the solvent to 90% ethanol significantly enhanced the wet ultimate tensile stress of ELAC threads to 109 MPa with a crosslinking degree of 65%. Furthermore, significantly higher adhesion and proliferation of hMSCs was observed in ELAC threads crosslinked with 2% genipin in 90% ethanol compared to 0.625% genipin in 1X PBS. In conclusion, ELAC threads with mechanical strength on par with native tendon have significant potential to be used as scaffolds in tendon tissue engineering applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. The initiation of embryonic-like collagen fibrillogenesis by adult human tendon fibroblasts when cultured under tension

    DEFF Research Database (Denmark)

    Bayer, Monika L; Yeung, Chin-Yan C; Kadler, Karl E

    2010-01-01

    Tendon fibroblasts synthesize collagen and form fibrils during embryonic development, but to what extent mature fibroblasts are able to recapitulate embryonic development and develop normal tendon structure is unknown. The present study examined the capability of mature human tendon fibroblasts t...

  16. Corticosteroid administration alters the mechanical properties of isolated collagen fascicles in rat-tail tendon

    DEFF Research Database (Denmark)

    Haraldsson, B T; Aagaard, P; Crafoord-Larsen, D

    2009-01-01

    Overload tendon injuries are frequent in recreational and elite sports. The optimal treatment strategy remains unknown, but local administration of corticosteroids is one common treatment option. The direct effects of the corticosteroid administration on the tissue are not fully understood....... The present study examined the biomechanical effects of intratendinous corticosteroid injections on healthy rat-tail tendon collagen fascicles. A total of 24 Wistar male rats were divided into (A) a corticosteroid group where the animals were injected in the tail tendon with methylprednisolone acetate, 1.0 m...

  17. Development of a reinforced electrochemically aligned collagen bioscaffold for tendon tissue engineering applications

    Science.gov (United States)

    Uquillas Paredes, Jorge Alfredo

    Type-I collagen is a promising biomaterial that can be used to synthesize bioscaffolds as a strategy to regenerate and repair damaged tendons. The existing in vitro prepared collagen bioscaffolds are in the form of gels, foams, or extruded fibers. These bioscaffolds readily present sites for attachment of biological factors and cells; however, they have extremely poor biomechanical properties in comparison to the properties of native tendons. The biomechanical function of type-I collagen bioscaffolds needs to be elevated to the level of natural tissues for this biomaterial to replace mechanically challenged tendons in a functionally meaningful way. The overall goal of this dissertation is to develop a reinforced electrochemically aligned collagenous bioscaffold for applications in tendon tissue engineering. The bioscaffold is synthesized by a unique electrochemical process via isoelectric focusing (IEF) to attain a very high degree of molecular alignment and packing density. This dissertation presents progress made on four aims: A) development of simple and descriptive electrochemical theory via the mathematical model of IEF and the forces acting on collagen alignment under an electric field; B) optimization of the post-alignment PBS treatment step to achieve d- banding pattern in uncrosslinked electrochemically aligned collagen (ELAC) bioscaffolds; C) optimization of the best crosslinking protocol to produce the strongest possible ELAC biomaterial with excellent cellular compatibility; and D) in vivo evaluation of the biocompatibility and biodegradability properties of electronically aligned collagen bioscaffolds. The results of this dissertation provide strong evidence showing that reinforced ELAC bioscaffolds could be used clinically in the future to repair damaged tendons.

  18. Evolutionary origins of C-terminal (GPPn 3-hydroxyproline formation in vertebrate tendon collagen.

    Directory of Open Access Journals (Sweden)

    David M Hudson

    Full Text Available Approximately half the proline residues in fibrillar collagen are hydroxylated. The predominant form is 4-hydroxyproline, which helps fold and stabilize the triple helix. A minor form, 3-hydroxyproline, still has no clear function. Using peptide mass spectrometry, we recently revealed several previously unknown molecular sites of 3-hydroxyproline in fibrillar collagen chains. In fibril-forming A-clade collagen chains, four new partially occupied 3-hydroxyproline sites were found (A2, A3, A4 and (GPPn in addition to the fully occupied A1 site at Pro986. The C-terminal (GPPn motif has five consecutive GPP triplets in α1(I, four in α2(I and three in α1(II, all subject to 3-hydroxylation. The evolutionary origins of this substrate sequence were investigated by surveying the pattern of its 3-hydroxyproline occupancy from early chordates through amphibians, birds and mammals. Different tissue sources of type I collagen (tendon, bone and skin and type II collagen (cartilage and notochord were examined by mass spectrometry. The (GPPn domain was found to be a major substrate for 3-hydroxylation only in vertebrate fibrillar collagens. In higher vertebrates (mouse, bovine and human, up to five 3-hydroxyproline residues per (GPPn motif were found in α1(I and four in α2(I, with an average of two residues per chain. In vertebrate type I collagen the modification exhibited clear tissue specificity, with 3-hydroxyproline prominent only in tendon. The occupancy also showed developmental changes in Achilles tendon, with increasing 3-hydroxyproline levels with age. The biological significance is unclear but the level of 3-hydroxylation at the (GPPn site appears to have increased as tendons evolved and shows both tendon type and developmental variations within a species.

  19. Targeted Deletion of Collagen V in Tendons and Ligaments Results in a Classic Ehlers-Danlos Syndrome Joint Phenotype

    Science.gov (United States)

    Sun, Mei; Connizzo, Brianne K.; Adams, Sheila M.; Freedman, Benjamin R.; Wenstrup, Richard J.; Soslowsky, Louis J.; Birk, David E.

    2016-01-01

    Collagen V mutations underlie classic Ehlers-Danlos syndrome, and joint hypermobility is an important clinical manifestation. We define the function of collagen V in tendons and ligaments, as well as the role of alterations in collagen V expression in the pathobiology in classic Ehlers-Danlos syndrome. A conditional Col5a1flox/flox mouse model was bred with Scleraxis-Cre mice to create a targeted tendon and ligament Col5a1-null mouse model, Col5a1Δten/Δten. Targeting was specific, resulting in collagen V–null tendons and ligaments. Col5a1Δten/Δten mice demonstrated decreased body size, grip weakness, abnormal gait, joint laxity, and early-onset osteoarthritis. These gross changes were associated with abnormal fiber organization, as well as altered collagen fibril structure with increased fibril diameters and decreased fibril number that was more severe in a major joint stabilizing ligament, the anterior cruciate ligament (ACL), than in the flexor digitorum longus tendon. The ACL also had a higher collagen V content than did the flexor digitorum longus tendon. The collagen V–null ACL and flexor digitorum longus tendon both had significant alterations in mechanical properties, with ACL exhibiting more severe changes. The data demonstrate critical differential regulatory roles for collagen V in tendon and ligament structure and function and suggest that collagen V regulatory dysfunction is associated with an abnormal joint phenotype, similar to the hypermobility phenotype in classic Ehlers-Danlos syndrome. PMID:25797646

  20. Uniform spatial distribution of collagen fibril radii within tendon implies local activation of pC-collagen at individual fibrils

    CERN Document Server

    Rutenberg, Andrew D; Kreplak, Laurent

    2016-01-01

    Collagen fibril cross-sectional radii show no systematic variation between the interior and the periphery of fibril bundles, indicating an effectively constant rate of collagen incorporation into fibrils throughout the bundle. Such spatially homogeneous incorporation constrains the extracellular diffusion of collagen precursors from sources at the bundle boundary to sinks at the growing fibrils. With a coarse-grained diffusion equation we determine stringent bounds, using parameters extracted from published experimental measurements of tendon development. From the lack of new fibril formation after birth, we further require that the concentration of diffusing precursors stays below the critical concentration for fibril nucleation. We find that the combination of the diffusive bound, which requires larger concentrations to ensure homogeneous fibril radii, and lack of nucleation, which requires lower concentrations, is only marginally consistent with fully-processed collagen using conservative bounds. More real...

  1. Tenomodulin is Required for Tendon Endurance Running and Collagen I Fibril Adaptation to Mechanical Load

    Directory of Open Access Journals (Sweden)

    Sarah Dex

    2017-06-01

    Full Text Available Tendons are dense connective tissues that attach muscles to bone with an indispensable role in locomotion because of their intrinsic properties of storing and releasing muscle- generated elastic energy. Tenomodulin (Tnmd is a well-accepted gene marker for the mature tendon/ligament lineage and its loss-of -function in mice leads to a phenotype with distinct signs of premature aging on tissue and stem/progenitor cell levels. Based on these findings, we hypothesized that Tnmd might be an important factor in the functional performance of tendons. Firstly, we revealed that Tnmd is a mechanosensitive gene and that the C-terminus of the protein co-localize with collagen I-type fibers in the extracellular matrix. Secondly, using an endurance training protocol, we compared Tnmd knockout mice with wild types and showed that Tnmd deficiency leads to significantly inferior running performance that further worsens with training. In these mice, endurance running was hindered due to abnormal response of collagen I cross-linking and proteoglycan genes leading to an inadequate collagen I fiber thickness and elasticity. In sum, our study demonstrates that Tnmd is required for proper tendon tissue adaptation to endurance running and aids in better understanding of the structural-functional relationships of tendon tissues.

  2. 3-D ultrastructure and collagen composition of healthy and overloaded human tendon

    DEFF Research Database (Denmark)

    Pingel, Jessica; Lu, Yinhui; Starborg, Tobias

    2014-01-01

    tendons of six individuals with clinically diagnosed tendinopathy who had no evidence of cholesterol, uric acid and amyloid accumulation. Biochemical analyses of collagen III/I ratio were performed on all six individuals, and electron microscope analysis using transmission electron microscopy and serial...

  3. Ovine tendon collagen: Extraction, characterisation and fabrication of thin films for tissue engineering applications.

    Science.gov (United States)

    Fauzi, M B; Lokanathan, Y; Aminuddin, B S; Ruszymah, B H I; Chowdhury, S R

    2016-11-01

    Collagen is the most abundant extracellular matrix (ECM) protein in the human body, thus widely used in tissue engineering and subsequent clinical applications. This study aimed to extract collagen from ovine (Ovis aries) Achilles tendon (OTC), and to evaluate its physicochemical properties and its potential to fabricate thin film with collagen fibrils in a random or aligned orientation. Acid-solubilized protein was extracted from ovine Achilles tendon using 0.35M acetic acid, and 80% of extracted protein was measured as collagen. SDS-PAGE and mass spectrometry analysis revealed the presence of alpha 1 and alpha 2 chain of collagen type I (col I). Further analysis with Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS) confirms the presence of triple helix structure of col I, similar to commercially available rat tail col I. Drying the OTC solution at 37°C resulted in formation of a thin film with randomly orientated collagen fibrils (random collagen film; RCF). Introduction of unidirectional mechanical intervention using a platform rocker prior to drying facilitated the fabrication of a film with aligned orientation of collagen fibril (aligned collagen film; ACF). It was shown that both RCF and ACF significantly enhanced human dermal fibroblast (HDF) attachment and proliferation than that on plastic surface. Moreover, cells were distributed randomly on RCF, but aligned with the direction of mechanical intervention on ACF. In conclusion, ovine tendon could be an alternative source of col I to fabricate scaffold for tissue engineering applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Changes in histoanatomical distribution of types I, III and V collagen promote adaptative remodeling in posterior tibial tendon rupture

    Directory of Open Access Journals (Sweden)

    Érika Satomi

    2008-01-01

    Full Text Available INTRODUCTION: Posterior tibial tendon dysfunction is a common cause of adult flat foot deformity, and its etiology is unknown. PURPOSE: In this study, we characterized the morphologic pattern and distribution of types I, III and V collagen in posterior tibial tendon dysfunction. METHOD: Tendon samples from patients with and without posterior tibial tendon dysfunction were stained by immunofluorescence using antibodies against types I, III and V collagen. RESULTS: Control samples showed that type V deposited near the vessels only, while surgically obtained specimens displayed type V collagen surrounding other types of collagen fibers in thicker adventitial layers. Type III collagen levels were also increased in pathological specimens. On the other hand, amounts of collagen type I, which represents 95% of the total collagen amount in normal tendon, were decreased in pathological specimens. CONCLUSION: Fibrillogenesis in posterior tibial tendon dysfunction is altered due to higher expression of types III and V collagen and a decreased amount of collagen type I, which renders the originating fibrils structurally less resistant to mechanical forces.

  5. Collagen fibril size and crimp morphology in ruptured and intact Achilles tendons

    DEFF Research Database (Denmark)

    Magnusson, S P; Qvortrup, K; Larsen, Jytte Overgaard

    2002-01-01

    The present study examined the hypothesis that collagen fibril diameter and crimp angle in ruptured human Achilles tendons differed from that of intact ones. Tissue samples were obtained from the central core (distal core) and the posterior periphery (distal superficial) at the rupture site...... reported that the injury did not occur during exceedingly large forces, and none experienced any symptoms in the days or months prior to the injury. Fibril diameter distribution showed no region-specific differences in either the ruptured or intact tendons for either group. However, in the distal core...... tendons. Crimp angle did not display any region-specific differences, or any difference between the rupture and intact tendons. In conclusion, these data suggest that although crimp morphology is unchanged there appears to be a site-specific loss of larger fibrils in the core and periphery of the Achilles...

  6. Pseudo-hyperelastic model of tendon hysteresis from adaptive recruitment of collagen type I fibrils.

    Science.gov (United States)

    Ciarletta, Pasquale; Dario, Paolo; Micera, Silvestro

    2008-02-01

    Understanding the functional relationship between the viscoelasticity and the morphology of soft collagenous tissues is fundamental for many applications in bioengineering science. This work presents a pseudo-hyperelastic constitutive theory aiming at describing the time-dependant hysteretic response of tendons subjected to uniaxial tensile loads. A macroscopic tendon is modeled as a composite homogeneous tissue with the anisotropic reinforcement of collagen type I fibrils. The tissue microstructure is considered as an adaptive network of fibrillar units connected in temporary junctions. The processes of breakage and reformation of active fibrils are thermally activated, and are occurring at random times. An internal softening variable and a dissipation energy function account for the adaptive arrangement of the fibrillar network in the pseudo-hyperelastic model. Cyclic uniaxial tensile tests have been performed in vitro on porcine flexor digital tendons. The theoretical predictions fit accurately the experimental stress-strain data both for the loading and the unloading processes. The hysteresis behavior reflects the improvement in the efficiency and performance of the motion of the muscle-tendon unit at high strain rates. The results of the model demonstrate the microstructural importance of proteoglycans in determining the functional viscoelastic adaptability of the macroscopic tendon.

  7. Treatment time of ultrasound therapy interferes with the organization of collagen fibers in rat tendons

    Directory of Open Access Journals (Sweden)

    Thiago S. Farcic

    2013-06-01

    Full Text Available BACKGROUND: The application time of therapeutic ultrasound is an infrequently studied dosimetric variable that affects tissue repair. OBJECTIVES: The aim of this study was to evaluate the effects of different treatment times of therapeutic ultrasound (US on the organization of collagen fibers in the tendons of rats. METHOD: Forty Wistar rats were selected (300±45 g, and the rats were divided into five groups (n=8 for each group: Control, without tenotomy or any treatment; tenotomy group, with tenotomy and without treatment; US groups (US1, US2, and US3, subjected to tenotomy and treated with US for one, two, or three minutes per area of the transducer, respectively. 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 analysis. RESULTS: The collagen fibers exhibited better aggregation and organization in the US3 group compared with the tenotomy group (p<0.05. CONCLUSIONS: The findings suggest that US applied for three minutes per treated area improves the organization of collagen fibers during rat tendon repair.

  8. Polarized Raman anisotropic response of collagen in tendon: towards 3D orientation mapping of collagen in tissues.

    Directory of Open Access Journals (Sweden)

    Leonardo Galvis

    Full Text Available In this study, polarized Raman spectroscopy (PRS was used to characterize the anisotropic response of the amide I band of collagen as a basis for evaluating three-dimensional collagen fibril orientation in tissues. Firstly, the response was investigated theoretically by applying classical Raman theory to collagen-like peptide crystal structures. The theoretical methodology was then tested experimentally, by measuring amide I intensity anisotropy in rat tail as a function of the orientation of the incident laser polarization. For the theoretical study, several collagen-like triple-helical peptide crystal structures obtained from the Protein Data Bank were rotated "in plane" and "out of plane" to evaluate the role of molecular orientation on the intensity of the amide I band. Collagen-like peptides exhibit a sinusoidal anisotropic response when rotated "in plane" with respect to the polarized incident laser. Maximal intensity was obtained when the polarization of the incident light is perpendicular to the molecule and minimal when parallel. In the case of "out of plane" rotation of the molecular structure a decreased anisotropic response was observed, becoming completely isotropic when the structure was perpendicular to the plane of observation. The theoretical Raman response of collagen was compared to that of alpha helical protein fragments. In contrast to collagen, alpha helices have a maximal signal when incident light is parallel to the molecule and minimal when perpendicular. For out-of-plane molecular orientations alpha-helix structures display a decreased average intensity. Results obtained from experiments on rat tail tendon are in excellent agreement with the theoretical predictions, thus demonstrating the high potential of PRS for experimental evaluation of the three-dimensional orientation of collagen fibers in biological tissues.

  9. Lower strength of the human posterior patellar tendon seems unrelated to mature collagen cross-linking and fibril morphology

    DEFF Research Database (Denmark)

    Hansen, Philip; Haraldsson, Bjarki Thor; Aagaard, Per

    2010-01-01

    -linking would parallel differences in material strength between the anterior and posterior tendon. Tendon fascicles were obtained from elective ACL surgery patients and tested micromechanically. Transmission electron microscopy was used to assess fibril morphology, and collagen cross-linking was determined...

  10. Increased proteolysis of collagen in an in vitro tensile overload tendon model.

    Science.gov (United States)

    Willett, Thomas L; Labow, Rosalind S; Avery, Nicholas C; Lee, J Michael

    2007-11-01

    Presently, there is a lack of fundamental understanding regarding changes in collagen's molecular state due to mechanical damage. The bovine tail tendon (BTT; steers approximately 30 months) was characterized and used as an in vitro model for investigating the effect of tensile mechanical overload on collagen susceptibility to proteolysis by acetyltrypsin and alpha-chymotrypsin. Two strain rates with a 1000-fold difference (0.01 and 10 s(-1)) were used, since molecular mechanisms that determine mechanical behavior were presumed to be strain rate dependent. First, it was determined that the BTTs were normal but immature tendons. Water content and collagen content (approx. 60% of wet weight and 80% of dry weight, respectively) and mechanical properties were all within the expected range. The collagen crosslinking was dominated by the intermediate crosslink hydroxylysinonorleucine. Second, tensile overload damage significantly enhanced proteolysis by acetyltrypsin and, to a lesser degree, by alpha-chymotrypsin. Interestingly, proteolysis by acetyltrypsin was greatest for specimens ruptured at 0.01 s(-1) and seemed to occur throughout the specimen. Understanding damage is important for insight into injuries (as in sports and trauma) and for better understanding of collagen fiber stability, durability, and damage mechanisms, aiding in the development of durable tissue-based products for mechanically demanding surgical applications.

  11. Type I collagen synthesis and degradation in peritendinous tissue after exercise determined by microdialysis in humans

    DEFF Research Database (Denmark)

    Langberg, Henning; Skovgaard, D; Petersen, L J

    1999-01-01

    1. Physical activity is known to increase type I collagen synthesis measured as the concentration of biomarkers in plasma. By the use of microdialysis catheters with a very high molecular mass cut-off value (3000 kDa) we aimed to determine local type I collagen synthesis and degradation...... catheters were placed in the peritendinous space ventral to the Achilles' tendon under ultrasound guidance and perfused with a Ringer-acetate solution containing 3H-labelled human type IV collagen and [15-3H(N)]PGE2 for in vivo recovery determination. Relative recovery was 37-59 % (range of the s...... increased in blood during running, and returned to baseline in the recovery period, whereas interstitial PGE2 concentration was elevated in the early recovery phase. 4. The findings of the present study indicate that acute exercise induces increased formation of type I collagen in peritendinous tissue...

  12. Cross-Linking in Collagen by Nonenzymatic Glycation Increases the Matrix Stiffness in Rabbit Achilles Tendon

    OpenAIRE

    Reddy, G. Kesava

    2004-01-01

    Nonenzymatic glycation of connective tissue matrix proteins is a major contributor to the pathology of diabetes and aging. Previously the author and colleagues have shown that nonenzymatic glycation significantly enhances the matrix stability in the Achilles tendon (Reddy et al., 2002, Arch. Biochem. Biophys., 399, 174–180). The present study was designed to gain further insight into glycation-induced collagen cross-linking and its relationship to matrix stiffness in the rabbit Achilles tendo...

  13. [Study on the acid hydrolysis, fiber remodeling and bionics mineralization of rat tail tendon collagen type Ⅰ].

    Science.gov (United States)

    Zhang, Zhan; Zhang, Chun; Guo, Qiaofeng

    2016-05-25

    Objective: To produce bionic bone material that is consistent with human bone in chemical composition and molecular structure using rat tail tendon collagen type Ⅰ. Methods: The type Ⅰcollagen derived from rat tail was extracted by acetic acid to form collagen fibers. The reconstructed collagen fibers were placed in the mineralized solution to mimic bone mineralization for 2-6 days. Bone mineralization was observed by transmission electron microscopy and electron diffraction.Results: Collagen fibers with characteristic D-Band structure were reconstructed by using rat tail tendon collagen type Ⅰ extracted with acid hydrolysis method. Transmission electron microscopy and electron diffraction showed that calcium hydroxyapatite precursor infiltrated into the collagen fibers, and the collagen fibers were partially mineralized after 2 days of mineralization; the collagen fibers were completely mineralized and bionic bone material of typeⅠ collagen/calcium hydroxyapatite was formed after 6 days of mineralization.Conclusion: The collagen type Ⅰ can be extracted from rat tail tendon by acid hydrolysis method, and can be reformed and mineralized to form the bionic bone material which mimics human bone in chemical composition and the molecular structure.

  14. Lysyl Oxidase Activity Is Required for Ordered Collagen Fibrillogenesis by Tendon Cells.

    Science.gov (United States)

    Herchenhan, Andreas; Uhlenbrock, Franziska; Eliasson, Pernilla; Weis, MaryAnn; Eyre, David; Kadler, Karl E; Magnusson, S Peter; Kjaer, Michael

    2015-06-26

    Lysyl oxidases (LOXs) are a family of copper-dependent oxido-deaminases that can modify the side chain of lysyl residues in collagen and elastin, thereby leading to the spontaneous formation of non-reducible aldehyde-derived interpolypeptide chain cross-links. The consequences of LOX inhibition in producing lathyrism are well documented, but the consequences on collagen fibril formation are less clear. Here we used β-aminoproprionitrile (BAPN) to inhibit LOX in tendon-like constructs (prepared from human tenocytes), which are an experimental model of cell-mediated collagen fibril formation. The improvement in structure and strength seen with time in control constructs was absent in constructs treated with BAPN. As expected, BAPN inhibited the formation of aldimine-derived cross-links in collagen, and the constructs were mechanically weak. However, an unexpected finding was that BAPN treatment led to structurally abnormal collagen fibrils with irregular profiles and widely dispersed diameters. Of special interest, the abnormal fibril profiles resembled those seen in some Ehlers-Danlos Syndrome phenotypes. Importantly, the total collagen content developed normally, and there was no difference in COL1A1 gene expression. Collagen type V, decorin, fibromodulin, and tenascin-X proteins were unaffected by the cross-link inhibition, suggesting that LOX regulates fibrillogenesis independently of these molecules. Collectively, the data show the importance of LOX for the mechanical development of early collagenous tissues and that LOX is essential for correct collagen fibril shape formation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Metrenperone enhances collagen turnover and remodeling in the early stages of healing of tendon injury in rabbit.

    Science.gov (United States)

    Oryan, Ahmad; Silver, Ian A; Goodship, Allen E

    2010-12-01

    This study evaluated the effects of metrenperone on healing of unilateral, collagenase-induced lesions in the Superficial Digital Flexor Tendons (SDFT) of rabbits. After controlled injury of the left SDFT, nine rabbits received daily treatment with metrenperone for 28 days. Another nine were untreated controls; in both groups the contra-lateral tendons served as uninjured controls. Histological and ultrastructural changes, mechanical properties, dry weight, collagen content, and amount of DNA in healing and control tendons were assessed 28 days after injury. Restoration of structural hierarchy was more organized in treated than in untreated tendons while cellularity was greater in the latter. At the ultrastructural level, collagen in treated lesions was predominantly in the form of small-diameter, new fibrils, with few large, old fibrils; in untreated lesions there was a high proportion of large, old fibrils but relatively few small, new ones. The amount of DNA in untreated injuries was much greater than in normal tendons, while in treated lesions it was not significantly different from that of uninjured controls. There were no significant differences in total collagen, stiffness and ultimate strength of injured, treated, and untreated tendons 28 days after injury. Both were significantly weaker than their corresponding contralaterals. The findings suggest that metrenperone had positive effects on collagen turnover, remodelling, and organization during acute inflammation and fibroplasia. Provided that the new fibrils subsequently matured in a normal manner, mechanical characteristics of the organized scar should be better than those of an untreated lesion.

  16. Lysylhydroxylation and non-reducible crosslinking of human supraspinatus tendon collagen: changes with age and in chronic rotator cuff tendinitis.

    Science.gov (United States)

    Bank, R A; TeKoppele, J M; Oostingh, G; Hazleman, B L; Riley, G P

    1999-01-01

    To investigate age related and site specific variations in turnover and chemistry of the collagen network in healthy tendons as well as the role of collagen remodelling in the degeneration of the supraspinatus tendon (ST-D) in rotator cuff tendinitis. Collagen content and the amount of hydroxylysine (Hyl), hydroxy-lysylpyridinoline (HP), lysylpyridinoline (LP), and the degree of non-enzymatic glycation (pentosidine) were investigated in ST-D and in normal human supraspinatus (ST-N) and biceps brachii tendons (BT-N) by high-performance liquid chromatography. In BT-N, tendons that served as control tissue as it shows rarely matrix abnormalities, pentosidine levels rise linearly with age (20-90 years), indicating little tissue remodelling (resulting in an undisturbed accumulation of pentosidine). A similar accumulation was observed in ST-N up to 50 years. At older ages, little pentosidine accumulation was observed and pentosidine levels showed large interindividual variability. This was interpreted as remodelling of collagen in normal ST after age 50 years because of microruptures (thus diluting old collagen with newly synthesised collagen). All degenerate ST samples showed decreased pentosidine levels compared with age matched controls, indicating extensive remodelling in an attempt to repair the tendon defect. Collagen content and the amount of Hyl, HP, and LP of ST-N and BT-N did not change with age. With the exception of collagen content, which did not differ, all parameters were significantly (p collagen content and had higher Hyl, HP, and LP levels than ST-N (p collagen. On the other hand, the clearly different profile of post-translational modifications in ST-D indicates that the newly deposited collagen network in degenerated tendons is qualitatively different. It is concluded that in ST-D the previously functional and carefully constructed matrix is replaced by aberrant collagen. This may result in a mechanically less stable tendon; as the supraspinatus is

  17. Mechanical properties of the equine superficial digital flexor tendon relate to specific collagen cross-link levels.

    Science.gov (United States)

    Thorpe, C T; Stark, R J F; Goodship, A E; Birch, H L

    2010-11-01

    Damage to the flexor tendons, particularly the superficial digital flexor tendon (SDFT), is one of the most common musculoskeletal injuries sustained by horses competing in all disciplines. Our previous work has shown that SDFTs from different individuals show a wide variation in mechanical strengths; this is important clinically as it may relate to predisposition to injury. The high mechanical strength of tendon relies on the correct orientation of collagen molecules within fibrils and stabilisation by the formation of chemical cross-links between collagen molecules. It is not known whether the variation in SDFT mechanical properties between individuals relates to differences in collagen cross-link levels. Enzyme-derived, intermolecular cross-linking of tendon collagen correlates with mechanical properties of the SDFT. SDFTs were collected from 38 horses and mechanically tested to failure. Structural and material properties were calculated from the load/deformation plot and cross-sectional area for each tendon. Following mechanical testing, pyrrolic cross-link levels were measured using a spectrophotometric assay for Ehrlich's reactivity and pyridinoline levels were quantified by HPLC. Cross-link levels were correlated with mechanical properties and statistical significance tested using a Pearson's correlation test. Pyrrole cross-link levels showed a significant positive correlation with ultimate stress (P = 0.004), yield stress (P = 0.003) and elastic modulus (P = 0.018) of the tendons, despite being a minor cross-link in these tendons. There was no significant correlation of mechanical properties with either hydroxylysyl- or lysyl-pyridinoline levels. Given the low absolute levels of pyrrole, we suggest that the correlation with high mechanical strength is through an indirect mechanism. Understanding the nature of the relationships between pyrrole cross-links, other matrix characteristics and tendon material properties may allow development of strategies to

  18. Mechanical properties and collagen cross-linking of the patellar tendon in old and young men

    DEFF Research Database (Denmark)

    Couppé, C; Hansen, P; Kongsgaard, M

    2009-01-01

    in animals but has never been examined in humans in vivo. In this study, we examined the mechanical properties and pyridinoline and pentosidine cross-link and collagen concentrations of the patellar tendon in vivo in old (OM) and young men (YM). Seven OM (67 +/- 3 years, 86 +/- 10 kg) and 10 YM (27 +/- 2...... lower in OM than in YM (0.49 +/- 0.27 vs. 0.73 +/- 0.14 mg/mg dry wt; P P P ... were higher in OM than in YM (73 +/- 13 vs. 11 +/- 2 mmol/mol; P

  19. Increased collagen synthesis rate during wound healing in muscle.

    Directory of Open Access Journals (Sweden)

    Shaobo Zhou

    Full Text Available Wound healing in muscle involves the deposition of collagen, but it is not known whether this is achieved by changes in the synthesis or the degradation of collagen. We have used a reliable flooding dose method to measure collagen synthesis rate in vivo in rat abdominal muscle following a surgical incision. Collagen synthesis rate was increased by 480% and 860% on days 2 and 7 respectively after surgery in the wounded muscle compared with an undamaged area of the same muscle. Collagen content was increased by approximately 100% at both day 2 and day 7. These results demonstrate that collagen deposition during wound healing in muscle is achieved entirely by an increase in the rate of collagen synthesis.

  20. The development of collagen-GAG scaffold-membrane composites for tendon tissue engineering.

    Science.gov (United States)

    Caliari, Steven R; Ramirez, Manuel A; Harley, Brendan A C

    2011-12-01

    Current tissue engineering approaches for tendon defects require improved biomaterials to balance microstructural and mechanical design criteria. Collagen-glycosaminoglycan (CG) scaffolds have shown considerable success as in vivo regenerative templates and in vitro constructs to study cell behavior. While these scaffolds possess many advantageous qualities, their mechanical properties are typically orders of magnitude lower than orthopedic tissues such as tendon. Taking inspiration from mechanically efficient core-shell composites in nature such as plant stems and porcupine quills, we have created core-shell CG composites that display high bioactivity and improved mechanical integrity. These composites feature integration of a low density, anisotropic CG scaffold core with a high density, CG membrane shell. CG membranes were fabricated via an evaporative process that allowed separate tuning of membrane thickness and elastic moduli and were found to be isotropic in-plane. The membranes were then integrated with an anisotropic CG scaffold core via freeze-drying and subsequent crosslinking. Increasing the relative thickness of the CG membrane shell was shown to increase composite tensile elastic modulus by as much as a factor of 36 in a manner consistent with predictions from layered composites theory. CG scaffold-membrane composites were found to support tendon cell viability, proliferation, and metabolic activity in vitro, suggesting they maintain sufficient permeability while demonstrating improved mechanical strength. This work suggests an effective, biomimetic approach for balancing strength and bioactivity requirements of porous scaffolds for tissue engineering. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Green Tea and Glycine Modulate the Activity of Metalloproteinases and Collagen in the Tendinitis of the Myotendinous Junction of the Achilles Tendon.

    Science.gov (United States)

    Vieira, Cristiano Pedrozo; De Oliveira, LetÍCia Prado; Da Ré Guerra, Flávia; Marcondes, Maria Cristina Cintra; Pimentel, Edson Rosa

    2016-07-01

    The myotendinous junction (MTJ) is the weakest element in the muscle-tendon unit of the heel, and thus the most susceptible to injuries. The scarcity of adequate treatments means that tendinitis is a major concern to athletes and other groups who depend on their physical fitness, although green tea and glycine have both been shown to have beneficial effects on the inflammation. The present study investigated the remodeling effects of green tea and glycine in the MTJ of rats with tendinitis. For this, male Wistar rats were divided into five groups: animals without tendinitis and animals with tendinitis; animals with tendinitis supplied with green tea; animals with tendinitis supplied with a glycine diet; animals with tendinitis supplied with a green tea and glycine diet. Tendinitis was induced and the treatment with green tea (700 mg/kg/day) and a 5% glycine diet lasted 7 days. The treatments regulated the activity of metalloproteinases (MMP)-2, -8, and -9, and induced the synthesis of type I collagen, glycosaminoglycans, and non-collagenous proteins. Changes were also noted in the compaction of the collagen molecules and the amount of tenocytes. When combined, green tea and glycine modulated the inflammatory process and induced the synthesis of the elements involved in the post-lesion recovery of the tissue. The data from the MTJ were different when compared with results already published using the whole Achilles tendon. These data indicate that each region of the inflamed tendon can exhibit different responses during the treatment and therefore, modify its extracellular matrix components to facilitate recovery and repair. Anat Rec, 299:918-928, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Effects of PDGF-BB delivery from heparinized collagen sutures on the healing of lacerated chicken flexor tendon in vivo.

    Science.gov (United States)

    Younesi, Mousa; Knapik, Derrick M; Cumsky, Jameson; Donmez, Baris Ozgur; He, Ping; Islam, Anowarul; Learn, Greg; McClellan, Philip; Bohl, Michael; Gillespie, Robert J; Akkus, Ozan

    2017-11-01

    Flexor tendon lacerations are traditionally repaired by using non-absorbable monofilament sutures. Recent investigations have explored to improve the healing process by growth factor delivery from the sutures. However, it is difficult to conjugate growth factors to nylon or other synthetic sutures. This study explores the performance of a novel electrochemically aligned collagen suture in a flexor tendon repair model with and without platelet derived growth factor following complete tendon laceration in vivo. Collagen suture was fabricated via electrochemical alignment process. Heparin was covalently bound to electrochemically aligned collagen sutures (ELAS) to facilitate affinity bound delivery of platelet-derived growth factor-BB (PDGF-BB). Complete laceration of the flexor digitorum profundus in the third digit of the foot was performed in 36 skeletally mature White Leghorn chickens. The left foot was used as the positive control. Animals were randomly divided into three groups: control specimens treated with standard nylon suture (n=12), specimens repaired with heparinated ELAS suture without PDGF-BB (n=12) and specimens repaired with heparinated ELAS suture with affinity bound PDGF-BB (n=12). Specimens were harvested at either 4weeks or 12weeks following tendon repair. Differences between groups were evaluated by the degree of gross tendon excursion, failure load/stress, stiffness/modulus, absorbed energy at failure, elongation/strain at failure. Quantitative histological scoring was performed to assess cellularity and vascularity. Closed flexion angle measurements demonstrated no significant differences in tendon excursion between the study groups at 4 or 12weeks. Biomechanical testing showed that the group treated with PDGF-BB bound heparinated ELAS suture had significantly higher stiffness and failure load (pBB bound suture had significantly higher ultimate tensile strength and Young's modulus (pBB improved biomechanics and vascularity during tendon healing

  3. Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types

    DEFF Research Database (Denmark)

    Heinemeier, K M; Olesen, J L; Haddad, F

    2007-01-01

    -9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve. RNA was extracted from medial gastrocnemius and Achilles tendon tissue 24 h after the last training bout, and mRNA levels for collagens I and III, TGF-beta-1, connective tissue growth factor (CTGF), lysyl oxidase (LOX...

  4. Effect of unloading followed by reloading on expression of collagen and related growth factors in rat tendon and muscle

    DEFF Research Database (Denmark)

    Heinemeier, K M; Olesen, J L; Haddad, F

    2009-01-01

    were subjected to hindlimb suspension (HS) for 7 or 14 days, followed by 2, 4, 8, or 16 days of reload (RL) (n = 8 in each group). Age-matched controls were included for day 0, day 14 HS, and day 16 RL (n = 8). mRNA expression levels for collagen I (COL1A1), collagen III (COL3A1), TGF-beta1, connective...... mRNA levels were unaltered by HS, although collagen III tended to decrease in muscle at day 7 HS. IGF-I isoforms were significantly induced in tendon after 7 days of HS (P day 14 HS (P

  5. Eccentric rehabilitation exercise increases peritendinous type I collagen synthesis in humans with Achilles tendinosis

    DEFF Research Database (Denmark)

    Langberg, Henning; Ellingsgaard, H; Madsen, T

    2007-01-01

    in the initially injured tendon (n=6; carboxyterminal propeptide of type I collagen (PICP): pre 3.9+/-2.5 microg/L to post 19.7+/-5.4 microg/L, P0.05). Collagen degradation, measured as carboxyterminal telopeptide region of type I collagen (ICTP), was not affected by training neither in the injured nor...... in the healthy tendons. The clinical effect of the 12 weeks of eccentric training was determined by using a standardized loading procedure of the Achilles tendons showing a decrease in pain in all the chronic injured tendons (VAS before 44+/-9, after 13+/-9; P...

  6. Collagen V-heterozygous and -null supraspinatus tendons exhibit altered dynamic mechanical behaviour at multiple hierarchical scales.

    Science.gov (United States)

    Connizzo, Brianne K; Han, Lin; Birk, David E; Soslowsky, Louis J

    2016-02-06

    Tendons function using a unique set of mechanical properties governed by the extracellular matrix and its ability to respond to varied multi-axial loads. Reduction of collagen V expression, such as in classic Ehlers-Danlos syndrome, results in altered fibril morphology and altered macroscale mechanical function in both clinical and animal studies, yet the mechanism by which changes at the fibril level lead to macroscale functional changes has not yet been investigated. This study addresses this by defining the multiscale mechanical response of wild-type, collagen V-heterozygous and -null supraspinatus tendons. Tendons were subjected to mechanical testing and analysed for macroscale properties, as well as microscale (fibre re-alignment) and nanoscale (fibril deformation and sliding) responses. In many macroscale parameters, results showed a dose-dependent response with severely decreased properties in the null group. In addition, both heterozygous and null groups responded to load faster than in wild-type tendons via earlier fibre re-alignment and fibril stretch. However, the heterozygous group exhibited increased fibril sliding, while the null group exhibited no fibril sliding. These studies demonstrate that dynamic responses play an important role in determining overall function and that collagen V is a critical regulator in the development of these relationships.

  7. Physical exercise can influence local levels of matrix metalloproteinases and their inhibitors in tendon-related connective tissue

    DEFF Research Database (Denmark)

    Koskinen, S O A; Heinemeier, K M; Olesen, J L

    2004-01-01

    Microdialysis studies indicate that mechanical loading of human tendon tissue during exercise or training can affect local synthesis and degradation of type I collagen. Degradation of collagen and other extracellular matrix proteins is controlled by an interplay between matrix metalloproteinases ...

  8. The effect of anisotropic collagen-GAG scaffolds and growth factor supplementation on tendon cell recruitment, alignment, and metabolic activity.

    Science.gov (United States)

    Caliari, Steven R; Harley, Brendan A C

    2011-08-01

    Current surgical and tissue engineering approaches for treating tendon injuries have shown limited success, suggesting the need for new biomaterial strategies. Here we describe the development of an anisotropic collagen-glycosaminoglycan (CG) scaffold and use of growth factor supplementation strategies to create a 3D platform for tendon tissue engineering. We fabricated cylindrical CG scaffolds with aligned tracks of ellipsoidal pores that mimic the native physiology of tendon by incorporating a directional solidification step into a conventional lyophilization strategy. By modifying the freezing temperature, we created a homologous series of aligned CG scaffolds with constant relative density and degree of anisotropy but a range of pore sizes (55-243 μm). Equine tendon cells showed greater levels of attachment, metabolic activity, and alignment as well as less cell-mediated scaffold contraction, when cultured in anisotropic scaffolds compared to an isotropic CG scaffold control. The anisotropic CG scaffolds also provided critical contact guidance cues for cell alignment. While tendon cells were randomly oriented in the isotropic control scaffold and the transverse (unaligned) plane of the anisotropic scaffolds, significant cell alignment was observed in the direction of the contact guidance cues in the longitudinal plane of the anisotropic scaffolds. Scaffold pore size was found to significantly influence tendon cell viability, proliferation, penetration into the scaffold, and metabolic activity in a manner predicted by cellular solids arguments. Finally, the addition of the growth factors PDGF-BB and IGF-1 to aligned CG scaffolds was found to enhance tendon cell motility, viability, and metabolic activity in dose-dependent manners. This work suggests a composite strategy for developing bioactive, 3D material systems for tendon tissue engineering. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Enhancement of tendon-bone healing via the combination of biodegradable collagen-loaded nanofibrous membranes and a three-dimensional printed bone-anchoring bolt.

    Science.gov (United States)

    Chou, Ying-Chao; Yeh, Wen-Lin; Chao, Chien-Lin; Hsu, Yung-Heng; Yu, Yi-Hsun; Chen, Jan-Kan; Liu, Shih-Jung

    A composite biodegradable polymeric model was developed to enhance tendon graft healing. This model included a biodegradable polylactide (PLA) bolt as the bone anchor and a poly(D,L-lactide-co-glycolide) (PLGA) nanofibrous membrane embedded with collagen as a biomimic patch to promote tendon-bone interface integration. Degradation rate and compressive strength of the PLA bolt were measured after immersion in a buffer solution for 3 months. In vitro biochemical characteristics and the nanofibrous matrix were assessed using a water contact angle analyzer, pH meter, and tetrazolium reduction assay. In vivo efficacies of PLGA/collagen nanofibers and PLA bolts for tendon-bone healing were investigated on a rabbit bone tunnel model with histological and tendon pullout tests. The PLGA/collagen-blended nanofibrous membrane was a hydrophilic, stable, and biocompatible scaffold. The PLA bolt was durable for tendon-bone anchoring. Histology showed adequate biocompatibility of the PLA bolt on a medial cortex with progressive bone ingrowth and without tissue overreaction. PLGA nanofibers within the bone tunnel also decreased the tunnel enlargement phenomenon and enhanced tendon-bone integration. Composite polymers of the PLA bolt and PLGA/collagen nanofibrous membrane can effectively promote outcomes of tendon reconstruction in a rabbit model. The composite biodegradable polymeric system may be useful in humans for tendon reconstruction.

  10. Collagenous hydrolysates from untraditional sources of proteins. Reaction condition and the yield of enzymatic hydrolysis of short cattle tendons.

    Science.gov (United States)

    Langmaier, F; Mladek, M; Kolomaznik, K; Sukop, S

    2001-08-01

    The effect of reaction conditions on the yield of enzymatic hydrolysis of short cattle tendons was examined using statistical scheme of factorial experiments 2(4). The duration of enzymatic purification of the starting material and of purified material denaturation processes, the protease concentration in reaction mixture and hydrolysis time were considered to be the main sources of reaction yield variation. An attempt was made to find the conditions leading to maximal yield of collagen hydrolysate.

  11. What is the impact of inflammation on the critical interplay between mechanical signaling and biochemical changes in tendon matrix?

    DEFF Research Database (Denmark)

    Kjaer, Michael; Bayer, Monika L; Eliasson, Pernilla

    2013-01-01

    Mechanical loading can influence tendon collagen homeostasis in animal models, while the dynamics of the human adult tendon core tissue are more debatable. Currently available data indicate that human tendon adaptation to loading may happen primarily in the outer tendon region. A role of inflamma......Mechanical loading can influence tendon collagen homeostasis in animal models, while the dynamics of the human adult tendon core tissue are more debatable. Currently available data indicate that human tendon adaptation to loading may happen primarily in the outer tendon region. A role...... of inflammation in this peritendinous adaptation is supported by a rise in inflammatory mediators in the peritendinous area after physiological mechanical loading in humans. This plays a role in the exercise-induced rise in tendon blood flow and peritendinous collagen synthesis. Although inflammatory activity can...... at rest nor after acute exercise display any enhanced inflammatory activity, and thus the basis for using anti-inflammatory medication to treat tendon overuse seems limited....

  12. The effect of mechanical stimulation on the maturation of TDSCs-poly(L-lactide-co-e-caprolactone)/collagen scaffold constructs for tendon tissue engineering.

    Science.gov (United States)

    Xu, Yuan; Dong, Shiwu; Zhou, Qiang; Mo, Xiumei; Song, Lei; Hou, Tianyong; Wu, Jinglei; Li, Songtao; Li, Yudong; Li, Pei; Gan, Yibo; Xu, Jianzhong

    2014-03-01

    Mechanical stimulation plays an important role in the development and remodeling of tendons. Tendon-derived stem cells (TDSCs) are an attractive cell source for tendon injury and tendon tissue engineering. However, these cells have not yet been fully explored for tendon tissue engineering application, and there is also lack of understanding to the effect of mechanical stimulation on the maturation of TDSCs-scaffold construct for tendon tissue engineering. In this study, we assessed the efficacy of TDSCs in a poly(L-lactide-co-ε-caprolactone)/collagen (P(LLA-CL)/Col) scaffold under mechanical stimulation for tendon tissue engineering both in vitro and in vivo, and evaluated the utility of the transplanted TDSCs-scaffold construct to promote rabbit patellar tendon defect regeneration. TDSCs displayed good proliferation and positive expressed tendon-related extracellular matrix (ECM) genes and proteins under mechanical stimulation in vitro. After implanting into the nude mice, the fluorescence imaging indicated that TDSCs had long-term survival, and the macroscopic evaluation, histology and immunohistochemistry examinations showed high-quality neo-tendon formation under mechanical stimulation in vivo. Furthermore, the histology, immunohistochemistry, collagen content assay and biomechanical testing data indicated that dynamically cultured TDSCs-scaffold construct could significantly contributed to tendon regeneration in a rabbit patellar tendon window defect model. TDSCs have significant potential to be used as seeded cells in the development of tissue-engineered tendons, which can be successfully fabricated through seeding of TDSCs in a P(LLA-CL)/Col scaffold followed by mechanical stimulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. A biochemical study of the distribution of collagen and its crosslinks in knee ligaments and the patellar tendon.

    Science.gov (United States)

    Hanada, Mitsuru; Takahashi, Masaaki; Suzuki, Daisuke; Abe, Masashi; Matsuyama, Yukihiro

    2014-01-01

    The purpose of this study was to investigate biochemical differences in collagen crosslinks from different locations within the ligaments and a tendon of the human knee. The anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), lateral collateral ligament (LCL), and patellar tendon (PT) were obtained from 24 cadavers (13 men and 11 women) whose average age at the time of death was 84.8 years. Ligaments and PT samples were obtained from the femoral and tibial insertions and the midsubstance. Hydroxyproline (Hyp) and collagen crosslinks, including pyridinoline (Pyr) and pentosidine (Pen), were compared among the different sites. The midsubstance Hyp concentration was greater than at the femoral and tibial insertions in the ACL (p = 0.00124 and 0.000255, respectively) and PCL (p = 0.00036 and 0.042, respectively). The Pyr:collagen ratio did not differ among sites in any of the ligaments or PT. The Pen:collagen ratio at the midsubstance was greater than at the femoral and tibial insertions in the ACL (p = 0.00022 and 0.00025, respectively) and LCL (p = 0.000081 and 0.000021, respectively) and was greater at the femoral insertion in the MCL (p = 0.00010). The mature collagen crosslink Pyr was not different in distribution in knee ligaments and the PT. Pen increased at the midsubstance ligaments and the PT. As increased Pen may represent ligament degeneration, this may indicate that degeneration may progress more rapidly at the midsubstance than at the insertion sites of a ligament.

  14. Heparinized collagen sutures for sustained delivery of PDGF-BB: Delivery profile and effects on tendon-derived cells In-Vitro.

    Science.gov (United States)

    Younesi, Mousa; Donmez, Baris Ozgur; Islam, Anowarul; Akkus, Ozan

    2016-09-01

    Suturing is the standard of repair for lacerated flexor tendons. Past studies focused on delivering growth factors to the repair site by incorporating growth factors to nylon sutures which are commonly used in the repair procedure. However, conjugation of growth factors to nylon or other synthetic sutures is not straightforward. Collagen holds promise as a suture material by way of providing chemical sites for conjugation of growth factors. On the other hand, collagen also needs to be reconstituted as a mechanically robust thread that can be sutured. In this study, we reconstituted collagen solutions as suturable collagen threads by using linear electrochemical compaction. Prolonged release of PDGF-BB (Platelet derived growth factor-BB) was achieved by covalent bonding of heparin to the collagen sutures. Tensile mechanical tests of collagen sutures before and after chemical modification indicated that the strength of sutures following chemical conjugation stages was not compromised. Strength of lacerated tendons sutured with epitendinous collagen sutures (11.2±0.7N) converged to that of the standard nylon suture (14.9±2.9N). Heparin conjugation of collagen sutures didn't affect viability and proliferation of tendon-derived cells and prolonged the PDGF-BB release up to 15days. Proliferation of cells seeded on PDGF-BB incorporated collagen sutures was about 50% greater than those seeded on plain collagen sutures. Collagen that is released to the media by the cells increased by 120% under the effects of PDGF-BB and collagen production by cells was detectable by histology as of day 21. Addition of PDGF-BB to collagen sutures resulted in a moderate decline in the expression of the tendon-associated markers scleraxis, collagen I, tenomodulin, and COMP; however, expression levels were still greater than the cells seeded on collagen gel. The data indicate that the effects of PDGF-BB on tendon-derived cells mainly occur through increased cell proliferation and that longer

  15. Lyophilized non-denatured type-I collagen (Condress) extracted from bovine Achilles' tendon and suitable for clinical use.

    Science.gov (United States)

    Beghé, F; Menicagli, C; Neggiani, P; Zampieri, A; Trallori, L; Teta, E; Rosini, S

    1992-01-01

    On account of the biological role of collagen in wound healing, and because of its biocompatibility, the use of heterologous collagen-based devices is becoming more widespread. Here we describe the extractive procedure and properties of a lyophilized type-I collagen (Condress) suitable for clinical use. Condress is extracted from bovine Achilles' tendon through a non-denaturing procedure in the absence of proteolytic enzymes. It has not been submitted to a chemical cross-linking process before lyophilization. Chemical identification of Condress as type-I acid-insoluble collagen has been carried out by evaluation of total nitrogen and hydroxyproline contents and by chromatographic examination. Electrophoretic analysis and morphological examination by electron microscopy confirm that the procedure employed to extract collagen does not alter the polypeptidic composition of the molecule and its structure. A gamma-ray dose between 0.5 and 1.5 Mrad is quite adequate to sterilize the final product and certainly devoid of degradative effect. The finished product has a special (peculiar) absorbing capacity, immersion time, strain resistance, wrinkling temperature and enzymatic digestion time. It is a nonallergenic product suitable for clinical use. When it has been applied in chronic leg ulcers, pressure sores, or reconstructive surgery, Condress seems to substantially improve wound repair.

  16. The adaptability of tendon to loading differs in men and women

    DEFF Research Database (Denmark)

    Magnusson, S Peter; Hansen, Mette; Langberg, Henning

    2007-01-01

    The reason why women sustain more soft tissue injury than men during physical activity is unknown. Connective tissue properties and extracellular matrix adaptability in human tendon were investigated in models that addressed biochemical, physiological and biomechanical aspects of tendon connective...... tissue in response to mechanical loading. Habitual training resulted in a larger patellar tendon in men but not in women. Following an acute bout of exercise, men had an elevated tendon collagen synthesis rate and this effect was less pronounced or absent in women. Moreover, levels of circulating...... oestrogen affected the acute exercise-related increase in collagen synthesis. Finally, the mechanical strength of isolated tendon collagen fascicles in men surpassed that of women. Thus, compared to men, women have (i) an attenuated tendon hypertrophy response to habitual training; (ii) a lower tendon...

  17. Asiaticoside induces cell proliferation and collagen synthesis in human dermal fibroblasts

    Directory of Open Access Journals (Sweden)

    Linda Yuliati

    2015-12-01

    Asiaticoside induces HDF proliferation and type I and III collagen synthesis in a time- and dose-dependent pattern. Asiaticoside has a similar effect as retinoic acid on type I and type III collagen synthesis.

  18. Endoplasmic reticulum stress inhibits collagen synthesis independent of collagen-modifying enzymes in different chondrocyte populations and dermal fibroblasts

    NARCIS (Netherlands)

    Vonk, Lucienne A.; Doulabi, Behrouz Zandieh; Huang, Chun-Ling; Helder, Marco N.; Everts, Vincent; Bank, Ruud A.

    Chondrocytes respond to glucose deprivation with a decreased collagen synthesis due to disruption of a proper functioning of the endoplasmic reticulum (ER): ER stress. Since the mechanisms involved in the decreased synthesis are unknown, we have investigated whether chaperones and collagen-modifying

  19. Endoplasmic reticulum stress inhibits collagen synthesis independent of collagen-modifying enzymes in different chondrocyte populations and dermal fibroblasts

    NARCIS (Netherlands)

    Vonk, L.A.; Doulabi, B.Z.; Huang, C.L.; Helder, M.N.; Everts, V.; Bank, R.A.

    2010-01-01

    Chondrocytes respond to glucose deprivation with a decreased collagen synthesis due to disruption of a proper functioning of the endoplasmic reticulum (ER): ER stress. Since the mechanisms involved in the decreased synthesis are unknown, we have investigated whether chaperones and collagen-modifying

  20. Sex Hormones and Tendon

    DEFF Research Database (Denmark)

    Hansen, Mette; Kjaer, Michael

    2016-01-01

    The risk of overuse and traumatic tendon and ligament injuries differ between women and men. Part of this gender difference in injury risk is probably explained by sex hormonal differences which are specifically distinct during the sexual maturation in the teenage years and during young adulthood....... The effects of the separate sex hormones are not fully elucidated. However, in women, the presence of estrogen in contrast to very low estrogen levels may be beneficial during regular loading of the tissue or during recovering after an injury, as estrogen can enhance tendon collagen synthesis rate. Yet...

  1. Order parameters of the orientation distribution of collagen fibers in Achilles tendon by 1H NMR of multipolar spin states.

    Science.gov (United States)

    Fechete, R; Demco, D E; Blümich, B

    2003-12-01

    The angular distribution function of collagen fibrils in a sheep Achilles tendon was investigated by (1)H NMR of multipolar spin states represented by dipolar-encoded longitudinal magnetization and double-quantum filtered signals. For the first time the angular distribution function based on the Legendre moment expansion is used. Order parameters were obtained from the anisotropy of (1)H residual dipolar couplings of bond water, which were determined model-free from the excitation efficiency of the multipolar spin states and from double-quantum filtered line splitting. The orientation distribution function of collagen fibrils in Achilles tendon measured from the anisotropy of the residual dipolar couplings is characterized by the average values of beta0 = 1.8+/-0.2 degrees and order parameters [P2] = 0.93+/-0.04, [P4] = 0.78+/-0.04 and [P6] = 0.58+/-0.04. The order of many biological tissues in the presence of ageing, injuries or regeneration can be quantified by the order parameters of the angular distribution function. Copyright 2003 John Wiley & Sons, Ltd.

  2. Effect of an aqueous extract of Phaseolus vulgaris on the properties of tail tendon collagen of rats with streptozotocin-induced diabetes

    OpenAIRE

    L. Pari; S. Venkateswaran

    2003-01-01

    Changes in the structural and functional properties of collagen caused by advanced glycation might be of importance for the etiology of late complications in diabetes. The present study was undertaken to investigate the influence of oral administration of aqueous pod extract (200 mg/kg body weight) of Phaseolus vulgaris, an indigenous plant used in Ayurvedic Medicine in India, on collagen content and characteristics in the tail tendon of streptozotocin-diabetic rats. In diabetic rats, collage...

  3. Lysyl oxidase activity is required for ordered collagen fibrillogenesis by tendon cells

    DEFF Research Database (Denmark)

    Herchenhan, Andreas; Uhlenbrock, Franziska Katharina; Eliasson, Pernilla

    2015-01-01

    to structurally abnormal collagen fibrils with irregular profiles and widely dispersed diameters. Of special interest, the abnormal fibril profiles resembled those seen in some Ehlers-Danlos Syndrome phenotypes. Importantly, the total collagen content developed normally, and there was no difference in COL1A1 gene...

  4. Increase in tendon protein synthesis in response to insulin-like growth factor-I is preserved in elderly men

    DEFF Research Database (Denmark)

    Nielsen, Rie Harboe; Holm, Lars; Malmgaard-Clausen, Nikolaj Mølkjær

    2014-01-01

    Insulin-like growth factor-I (IGF-I) is known to be an anabolic factor in tendon, and the systemic levels are reduced with aging. However, it is uncertain how tendon fibroblasts are involved in tendon aging and how aging cells respond to IGF-I. The purpose of this study was to investigate...... the in vivo IGF-I stimulation of tendon protein synthesis in elderly compared with young men. We injected IGF-I in the patellar tendons of young (n = 11, 20-30 yr of age) and old (n = 11, 66-75 yr of age) men, and the acute fractional synthesis rate (FSR) of tendon protein was measured with the stable isotope......, despite lower systemic IGF-I levels in the old group. This could indicate that the changed phenotype in aging tendon is not caused by decreased fibroblast function....

  5. p38 MAPK signaling in postnatal tendon growth and remodeling.

    Directory of Open Access Journals (Sweden)

    Andrew J Schwartz

    Full Text Available Tendon is a dynamic tissue whose structure and function is influenced by mechanical loading, but little is known about the fundamental mechanisms that regulate tendon growth and remodeling in vivo. Data from cultured tendon fibroblasts indicated that the p38 MAPK pathway plays an important role in tendon fibroblast proliferation and collagen synthesis in vitro. To gain greater insight into the mechanisms of tendon growth, and explore the role of p38 MAPK signaling in this process, we tested the hypotheses that inducing plantaris tendon growth through the ablation of the synergist Achilles tendon would result in rapid expansion of a neotendon matrix surrounding the original tendon, and that treatment with the p38 MAPK inhibitor SB203580 would prevent this growth. Rats were treated with vehicle or SB203580, and subjected to synergist ablation by bilateral tenectomy of the Achilles tendon. Changes in histological and biochemical properties of plantaris tendons were analyzed 3, 7, or 28 days after overload, and comparisons were made to non-overloaded animals. By 28 days after overload, tendon mass had increased by 30% compared to non-overloaded samples, and cross-sectional area (CSA increased by around 50%, with most of the change occurring in the neotendon. The expansion in CSA initially occurred through the synthesis of a hyaluronic acid rich matrix that was progressively replaced with mature collagen. Pericytes were present in areas of active tendon growth, but never in the original tendon ECM. Inhibition of p38 MAPK resulted in a profound decrease in IL6 expression, and had a modest effect on the expression of other ECM and cell proliferation genes, but had a negligible impact on overall tendon growth. The combined results from this study provided novel insights into tendon mechanobiology, and suggest that p38 MAPK signaling does not appear to be necessary for tendon growth in vivo.

  6. Tendon healing in vivo. An experimental model.

    Science.gov (United States)

    Abrahamsson, S O; Lundborg, G; Lohmander, L S

    1989-01-01

    Flexor tendon segments were incubated in a diffusion chamber in the subcutis of rabbits. Tendons incubated up to 6 weeks in the diffusion chamber showed proliferating and migrating cells from the epitenon cell layer as well as viable endotenon cells. Explants frozen in liquid nitrogen prior to incubation showed no signs of extrinsic cell contamination and remained non-viable indicating that no cell penetration occurred through the Millipore filter and that cell division seen in non-frozen and incubated tendons was an expression of intrinsic cellular proliferative capacity of the tendon. In tendon segments incubated in chambers for three weeks, collagen synthesis was reduced by 50% and the rate of cell proliferation measured as 3H-thymidine incorporation, was 15 times that of native tendons. Frozen and incubated tendons showed only traces of remaining matrix synthesis or cell proliferation. With this experimental model we have histologically and biochemically shown that tendons may survive and heal while the nutrition exclusively could be based on diffusion and the tendons have an intrinsic capacity of healing. The described model enables further studies on tendon healing and its regulation.

  7. The use of serologic markers for collagen synthesis and degradation in systemic sclerosis

    DEFF Research Database (Denmark)

    Heickendorff, Lene; Zachariae, Hugh; Bjerring, Peter

    1995-01-01

    BACKGROUND: Systemic sclerosis is characterized by excessive accumulation of collagen in all involved organs. Serum markers of collagen synthesis and degradation, the aminoterminal propeptide of type III procollagen (PIIINP), the carboxyterminal propeptide of type I procollagen (PICP), and the cr...

  8. Expression of insulin-like growth factor I, insulin-like growth factor binding proteins, and collagen mRNA in mechanically loaded plantaris tendon

    DEFF Research Database (Denmark)

    Olesen, Jens L; Heinemeier, Katja M; Haddad, Fadia

    2006-01-01

    . However, it is not known whether MGF is expressed and upregulated in mechanically loaded tendon. This study examined the effect of mechanical load on tendon collagen mRNA in relation to changes in the IGF-I systems mRNA expression. Data were collected at 2, 4, 8 and 16 days after surgical removal...... of synergistic muscle to the plantaris muscle of the rat, thus increasing the load to plantaris muscle and tendon. Nearly a doubling of the tendon mass was observed after 16 days of loading. A rapid rise in tendon procollagen III mRNA was seen after 2 days whereas the increase in procollagen I m......RNA was significant from day 8. MGF was expressed and upregulated in loaded tendon tissue with a faster response than IGF-I, which was increased from day 8. Finally, IGFBP-4 mRNA was increased with a time pattern similar to procollagen III, whereas IGFBP-5 decreased at day 8. In conclusion, loading of tendon tissue...

  9. Effect of aging and exercise on the tendon

    DEFF Research Database (Denmark)

    Svensson, Rene B; Heinemeier, Katja Maria; Couppé, Christian

    2016-01-01

    in humans, which likely reflects synthesis at the very periphery of the tendon rather than the core. Average collagen fibril diameter is largely unaffected by exercise, while there can be some hypertrophy of the whole tendon. In addition, it seems that resistance training can yield increased stiffness......Here, we review the literature on how tendons respond and adapt to ageing and exercise. With respect to aging, there are considerable changes early in life, but this seems to be maturation rather than aging per se. In vitro data indicate that aging is associated with a decreased potential for cell...... proliferation and a reduction in the number of stem/progenitor-like cells. Further, there is persuasive evidence that turnover in the core of the tendon after maturity is very slow or absent. Tendon fibril diameter, collagen content, and whole tendon size appear to be largely unchanged with aging, while...

  10. Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue

    OpenAIRE

    Papachroni, Katerina K.; Piperi, Christina; Levidou, Georgia; Korkolopoulou, Penelope; Pawelczyk, Leszek; Diamanti-Kandarakis, Evanthia; Papavassiliou, Athanasios G.

    2009-01-01

    Abstract Connective tissue components ? collagen types I, III and IV ? surrounding the ovarian follicles undergo drastic changes during ovulation. Abnormal collagen synthesis and increased volume and density of ovarian stroma characterize the polycystic ovary syndrome (PCOS). During the ovulatory process, collagen synthesis is regulated by prolyl hydroxylase and lysyl oxidase (LOX) activity in ovarian follicles. LOX catalyzes collagen and elastin cross-linking and plays essential role in coor...

  11. Electrophoretic analysis of type I collagen from bovine Achilles tendon: comparison between the extracted raw material and the freeze-dried product.

    Science.gov (United States)

    Menicagli, C; Giorgi, F

    1990-01-01

    The present study was aimed at verifying if the freeze-drying process has any effect on the polypeptide composition of the collagen extracted from bovine Achilles tendon in an acetic acid gelified form. Data from our laboratories showed that the freeze-drying process renders the collagen gel essentially insoluble; under these conditions the collagen sample can no longer be analyzed by gel electrphoresis. We found that treatment of the sample with pepsin in acid environment, followed by precipitation with ammonium sulphate yields an insoluble fraction that is susceptible of being analyzed by polyacrylamide gel electrophoresis. The The electrophoresis, run under standard conditions, shows that six major subunits, corresponding to alpha, beta and gamma polypeptides, can be revealed in the sample treated in this way. So the freeze-dried collagen exhibits a polypeptidic composition that is basically identical to that shown by the collagen gel, with regard to the fraction precipitated with ammonium sulphate. Otherwise the pattern of the enzymatic hydrolysis was investigated by measuring the hydroxyproline content, and so the collagen content using the 7.46 conversion factor from hydroxyproline to the scleroprotein collagen, in the various steps of the hydrolysis itself: the analytical results showed no differences between the freeze-dried collagen and the gelified form; this confirms that the lyophilization process does not alter the polypeptidic composition of the collagen in any way.

  12. COL6A3 protein deficiency in mice leads to muscle and tendon defects similar to human collagen VI congenital muscular dystrophy.

    Science.gov (United States)

    Pan, Te-Cheng; Zhang, Rui-Zhu; Markova, Dessislava; Arita, Machiko; Zhang, Yejia; Bogdanovich, Sasha; Khurana, Tejvir S; Bönnemann, Carsten G; Birk, David E; Chu, Mon-Li

    2013-05-17

    Collagen VI is a ubiquitously expressed extracellular microfibrillar protein. Its most common molecular form is composed of the α1(VI), α2(VI), and α3(VI) collagen α chains encoded by the COL6A1, COL6A2, and COL6A3 genes, respectively. Mutations in any of the three collagen VI genes cause congenital muscular dystrophy types Bethlem and Ullrich as well as intermediate phenotypes characterized by muscle weakness and connective tissue abnormalities. The α3(VI) collagen α chain has much larger N- and C-globular domains than the other two chains. Its most C-terminal domain can be cleaved off after assembly into microfibrils, and the cleavage product has been implicated in tumor angiogenesis and progression. Here we characterize a Col6a3 mutant mouse that expresses a very low level of a non-functional α3(VI) collagen chain. The mutant mice are deficient in extracellular collagen VI microfibrils and exhibit myopathic features, including decreased muscle mass and contractile force. Ultrastructurally abnormal collagen fibrils were observed in tendon, but not cornea, of the mutant mice, indicating a distinct tissue-specific effect of collagen VI on collagen I fibrillogenesis. Overall, the mice lacking normal α3(VI) collagen chains displayed mild musculoskeletal phenotypes similar to mice deficient in the α1(VI) collagen α chain, suggesting that the cleavage product of the α3(VI) collagen does not elicit essential functions in normal growth and development. The Col6a3 mouse mutant lacking functional α3(VI) collagen chains thus serves as an animal model for COL6A3-related muscular dystrophy.

  13. Observing Effects of Calcium/Magnesium Ions and pH Value on the Self-Assembly of Extracted Swine Tendon Collagen by Atomic Force Microscopy

    Directory of Open Access Journals (Sweden)

    Xuan Song

    2017-01-01

    Full Text Available Self-assembly of extracted collagen from swine trotter tendon under different conditions was firstly observed using atomic force microscopy; then the effects of collagen concentration, pH value, and metal ions to the topography of the collagen assembly were analyzed with the height images and section analysis data. Collagen assembly under 0.1 M, 0.2 M, 0.3 M CaCl2, and MgCl2 solutions in different pH values showed significant differences (P < 0.05 in the topographical properties including height, width, and roughness. With the concentration being increased, the width of collagen decreased significantly (P < 0.05. The width of collagen fibers was first increased significantly (P < 0.05 and then decreased with the increasing of pH. The collagen was assembled with network structure on the mica in solution with Ca2+ ions. However, it had shown uniformed fibrous structure with Mg2+ ions on the new cleaved mica sheet. In addition, the width of collagen fibrous was 31~58 nm in solution with Mg2+ but 21~50 nm in Ca2+ solution. The self-assembly collagen displayed various potential abilities to construct fibers or membrane on mica surfaces with Ca2+ ions and Mg2+ irons. Besides, the result of collagen self-assembly had shown more relations among solution pH value, metal ions, and collagen molecular concentration, which will provide useful information on the control of collagen self-assembly in tissue engineering and food packaging engineering.

  14. GH and IGF-I levels are positively associated with musculotendinous collagen expression: Experiments in acromegalic and GHD patients

    DEFF Research Database (Denmark)

    Doessing, Simon; Holm, Lars; Heinemeier, Katja

    2010-01-01

    OBJECTIVE: Disproportionate growth of musculoskeletal tissue is a major cause of morbidity in both acromegalic (ACRO) and GH-deficient (GHD) patients. GH/IGF1 is likely to play an important role in the regulation of tendon and muscle collagen. We hypothesized that the local production of collagen...... is associated with the level of GH/IGF1.DESIGN AND METHODS: As primary outcomes, collagen mRNA expression and collagen protein fractional synthesis rate (FSR) were determined locally in skeletal muscle and tendon in nine ACRO and nine GHD patients. Moreover, muscle myofibrillar protein synthesis and tendon...... collagen morphology were determined.RESULTS AND CONCLUSIONS: Muscle collagen I and III mRNA expression was higher in ACRO patients versus GHD patients (Pcollagen protein FSR did not differ significantly between ACRO and GHD patients in muscle (P=0.21) and tendon (P=0.15). IGF1Ea and IGF1Ec...

  15. Synthesis of type III collagen by fibroblasts from the embryonic chick cornea

    OpenAIRE

    1980-01-01

    Synthesis of collagen types I, II, III, and IV in cells from the embryonic chick cornea was studied using specific antibodies and immunofluorescence. Synthesis of radioactively labeled collagen types I and III was followed by fluorographic detection of cyanogen bromide peptides on polyacrylamide slab gels and by carboxymethylcellulose chromatography followed by disc gel electrophoresis. Type III collagen had been detected previously by indirect immunofluorescence in the corneal epithelial cel...

  16. Effect of an aqueous extract of Phaseolus vulgaris on the properties of tail tendon collagen of rats with streptozotocin-induced diabetes

    Directory of Open Access Journals (Sweden)

    L. Pari

    2003-07-01

    Full Text Available Changes in the structural and functional properties of collagen caused by advanced glycation might be of importance for the etiology of late complications in diabetes. The present study was undertaken to investigate the influence of oral administration of aqueous pod extract (200 mg/kg body weight of Phaseolus vulgaris, an indigenous plant used in Ayurvedic Medicine in India, on collagen content and characteristics in the tail tendon of streptozotocin-diabetic rats. In diabetic rats, collagen content (117.01 ± 6.84 mg/100 mg tissue as well as its degree of cross-linking was increased, as shown by increased extent of glycation (21.70 ± 0.90 µg glucose/mg collagen, collagen-linked fluorescence (52.8 ± 3.0 AU/µmol hydroxyproline, shrinkage temperature (71.50 ± 2.50ºC and decreased acid (1.878 ± 0.062 mg hydroxyproline/100 mg tissue and pepsin solubility (1.77 ± 0.080 mg hydroxyproline/100 mg tissue. The alpha/ß ratio of acid- (1.69 and pepsin-soluble (2.00 collagen was significantly decreased in streptozotocin-diabetic rats. Administration of P. vulgaris for 45 days to streptozotocin-diabetic rats significantly reduced the accumulation and cross-linking of collagen. The effect of P. vulgaris was compared with that of glibenclamide, a reference drug administered to streptozotocin-diabetic rats at the dose of 600 µg/kg body weight for 45 days by gavage. The effects of P. vulgaris (collagen content, 64.18 ± 1.97; extent of glycation, 12.00 ± 0.53; collagen-linked fluorescence, 33.6 ± 1.9; shrinkage temperature, 57.0 ± 1.0; extent of cross-linking - acid-soluble collagen, 2.572 ± 0.080, and pepsin-soluble collagen, 2.28 ± 0.112 were comparable with those of glibenclamide (collagen content, 71.5 ± 2.04; extent of glycation, 13.00 ± 0.60; collagen-linked fluorescence, 38.9 ± 2.0; shrinkage temperature, 59.0 ± 1.5; extent of cross-linking - acid-soluble collagen, 2.463 ± 0.078, and pepsin-soluble collagen, 2.17 ± 0.104. In

  17. Effect of an aqueous extract of Phaseolus vulgaris on the properties of tail tendon collagen of rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Pari, L; Venkateswaran, S

    2003-07-01

    Changes in the structural and functional properties of collagen caused by advanced glycation might be of importance for the etiology of late complications in diabetes. The present study was undertaken to investigate the influence of oral administration of aqueous pod extract (200 mg/kg body weight) of Phaseolus vulgaris, an indigenous plant used in Ayurvedic Medicine in India, on collagen content and characteristics in the tail tendon of streptozotocin-diabetic rats. In diabetic rats, collagen content (117.01 6.84 mg/100 mg tissue) as well as its degree of cross-linking was increased, as shown by increased extent of glycation (21.70 0.90 g glucose/mg collagen), collagen-linked fluorescence (52.8 3.0 AU/ mol hydroxyproline), shrinkage temperature (71.50 2.50 C) and decreased acid (1.878 0.062 mg hydroxyproline/100 mg tissue) and pepsin solubility (1.77 0.080 mg hydroxyproline/100 mg tissue). The alpha/ ratio of acid- (1.69) and pepsin-soluble (2.00) collagen was significantly decreased in streptozotocin-diabetic rats. Administration of P. vulgaris for 45 days to streptozotocin-diabetic rats significantly reduced the accumulation and cross-linking of collagen. The effect of P. vulgaris was compared with that of glibenclamide, a reference drug administered to streptozotocin-diabetic rats at the dose of 600 g/kg body weight for 45 days by gavage. The effects of P. vulgaris (collagen content, 64.18 1.97; extent of glycation, 12.00 0.53; collagen-linked fluorescence, 33.6 1.9; shrinkage temperature, 57.0 1.0; extent of cross-linking - acid-soluble collagen, 2.572 0.080, and pepsin-soluble collagen, 2.28 0.112) were comparable with those of glibenclamide (collagen content, 71.5 2.04; extent of glycation, 13.00 0.60; collagen-linked fluorescence, 38.9 2.0; shrinkage temperature, 59.0 1.5; extent of cross-linking - acid-soluble collagen, 2.463 0.078, and pepsin-soluble collagen, 2.17 0.104). In conclusion, administration of P. vulgaris pods had a positive influence on the

  18. Extracellular matrix adaptation of tendon and skeletal muscle to exercise

    DEFF Research Database (Denmark)

    Kjaer, Michael; Magnusson, Peter; Krogsgaard, Michael

    2006-01-01

    The extracellular matrix (ECM) of connective tissues enables linking to other tissues, and plays a key role in force transmission and tissue structure maintenance in tendons, ligaments, bone and muscle. ECM turnover is influenced by physical activity, and both collagen synthesis and metalloprotea...... is supported by findings of gender-related differences in the activation of collagen synthesis with exercise. These findings may provide the basis for understanding tissue overloading and injury in both tendons and skeletal muscle.......The extracellular matrix (ECM) of connective tissues enables linking to other tissues, and plays a key role in force transmission and tissue structure maintenance in tendons, ligaments, bone and muscle. ECM turnover is influenced by physical activity, and both collagen synthesis and metalloprotease...... is regulated by cyclooxygenase-2 (COX-2)-mediated pathways, and glucose uptake is regulated by specific pathways in tendons that differ from those in skeletal muscle. Chronic loading in the form of physical training leads both to increased collagen turnover as well as to some degree of net collagen synthesis...

  19. Impact of oral contraceptive use and menstrual phases on patellar tendon morphology, biochemical composition and biomechanical properties in female athletes

    DEFF Research Database (Denmark)

    Hansen, Mette; Couppe, Christian; Hansen, Christina S

    2013-01-01

    Introduction: Gender differences exist with regards to ligament and tendon injuries. Lower collagen synthesis has been observed in exercising females vs. males, and in users of oral contraceptives (OC) vs non-users, but it is unknown if OC will influence tendon biomechanics of females undergoing ...

  20. Hyperuricemic PRP in Tendon Cells

    Directory of Open Access Journals (Sweden)

    I. Andia

    2014-01-01

    Full Text Available Platelet-rich plasma (PRP is injected within tendons to stimulate healing. Metabolic alterations such as the metabolic syndrome, diabetes, or hyperuricemia could hinder the therapeutic effect of PRP. We hypothesise that tendon cells sense high levels of uric acid and this could modify their response to PRP. Tendon cells were treated with allogeneic PRPs for 96 hours. Hyperuricemic PRP did not hinder the proliferative actions of PRP. The gene expression pattern of inflammatory molecules in response to PRP showed absence of IL-1b and COX1 and modest expression of IL6, IL8, COX2, and TGF-b1. IL8 and IL6 proteins were secreted by tendon cells treated with PRP. The synthesis of IL6 and IL8 proteins induced by PRP is decreased significantly in the presence of hyperuricemia (P = 0.017 and P = 0.012, resp.. Concerning extracellular matrix, PRP-treated tendon cells displayed high type-1 collagen, moderate type-3 collagen, decorin, and hyaluronan synthase-2 expression and modest expression of scleraxis. Hyperuricemia modified the expression pattern of extracellular matrix proteins, upregulating COL1 (P = 0.036 and COMP (P = 0.012 and downregulating HAS2 (P = 0.012. Positive correlations between TGF-b1 and type-1 collagen (R = 0.905, P = 0.002 and aggrecan (R = 0.833, P = 0.010 and negative correlations between TGF-b1 and IL6 synthesis (R = −0.857, P = 0.007 and COX2 (R = −0.810, P = 0.015 were found.

  1. Effectiveness of xenogenous-based bovine-derived platelet gel embedded within a three-dimensional collagen implant on the healing and regeneration of the Achilles tendon defect in rabbits

    Science.gov (United States)

    Moshiri, Ali; Oryan, Ahmad; Meimandi-Parizi, Abdolhamid; Koohi-Hosseinabadi, Omid

    2014-01-01

    Background and objective: Tissue engineering is an option in reconstructing large tendon defects and managing their healing and regeneration. We designed and produced a novel xenogeneic-based bovine platelet, embedded it within a tissue-engineered collagen implant (CI) and applied it in an experimentally induced large tendon defect model in rabbits to test whether bovine platelets could stimulate tendon healing and regeneration in vivo. Methods: One hundred twenty rabbits were randomly divided into two experimental and pilot groups. In all the animals, the left Achilles tendon was surgically excised and the tendon edges were aligned by Kessler suture. Each group was then divided into three groups of control (no implant), treated with CI and treated with collagen-platelet implant. The pilot groups were euthanized at 10, 15, 30 and 40 days post-injury (DPI), and their gross and histologic characteristics were evaluated to study host–graft interaction mechanism. To study the tendon healing and its outcome, the experimental animals were tested during the experiment using hematologic, ultrasonographic and various methods of clinical examinations and then euthanized at 60 DPI and their tendons were evaluated by gross pathologic, histopathologic, scanning electron microscopic, biophysical and biochemical methods. Results: Bovine platelets embedded within a CI increased inflammation at short term while it increased the rate of implant absorption and matrix replacement compared with the controls and CI alone. Treatment also significantly increased diameter, density, amount, alignment and differentiation of the collagen fibrils and fibers and approximated the water uptake and delivery behavior of the healing tendons to normal contralaterals (p tendons and reduced peritendinous adhesion, muscle fibrosis and atrophy, and therefore, it improved the clinical scores and physical activity related to the injured limb when compared with the controls (p Achilles tendon in rabbit

  2. The effect of glucocorticoids on tendon cell viability in human tendon explants

    Science.gov (United States)

    Lui, Wai Ting; Chuen Fu, Sai; Man Lee, Kwong

    2009-01-01

    Background and purpose Previous studies on the culture of human tenocytes have shown that dexamethasone and triamcino-lone reduce cell viability, suppress cell proliferation, and reduce collagen synthesis. However, such cell cultures lack the extracellular matrix and three-dimensional structure of normal tendons, which affects their response to stimuli. We established a human tendon explant culture system and tested the effects of dexamethasone and triamcinolone on cell viability. Methods Primary human tendon explant cultures were prepared from healthy hamstring tendons. Tendon strips were harvested from hamstring tendons and cultured in 24-well plates in Dulbecco’s modification of Eagle’s Medium (DMEM) supplemented with 2% fetal calf serum. The tendon explants were treated with 0 μM (control), 10 μM, or 100 μM dexamethasone sodium phosphate or 0 μM (control), 10 μM, or 100 μM triamcinolone acetonide in DMEM for 96 h. Cell viability was measured by Alamar blue assay before and after glucocorticoid treatment. Results Incubation with 10 μM and 100 μM dexamethasone reduced cell viability in human tendon explants by 35% and 45%, respectively, as compared to a 6% increase in the controls (p = 0.01, mixed-effects ANOVA). Triamcinolone at 10 μM and 100 μM reduced cell viability by 33% and 36%, respectively, as compared to a 9% increase in the controls (p = 0.07, mixed-effects ANOVA). Interpretation Human tendon explant cultures can be used to study the effects of glucocorticoids on human tendon. Dexamethasone and triamcinolone suppress the cell viability of human tendon in its natural 3-dimensional environment with matrix anchorage. Human tendon explant cultures provide a species-specific model for further investigation of the effects of glucocorticoids on the metabolism of the extracellular matrix of human tendon, and on its mechanical properties. PMID:19421908

  3. Estradiol inhibits hepatic stellate cell area and collagen synthesis in the chicken liver.

    Science.gov (United States)

    Nishimura, Shotaro; Teshima, Akifumi; Kawabata, Fuminori; Tabata, Shoji

    2017-11-01

    Hepatic stellate cells (HSCs) are the main collagen-producing cells in the liver. The HSC area and amount of collagen fibers are different between male and female chickens. This study was performed to confirm the effect of estradiol on collagen synthesis in the growing chicken liver. Blood estradiol levels in chicks were compared at 4 and 8 weeks of age, and the collagen fibril network in liver tissue was observed at 8 weeks by scanning electron microscopy. Intraperitoneal administrations of estradiol and tamoxifen to male and female chicks, respectively, were performed daily from 5 to 8 weeks of age. The areas of HSCs and collagen contents were measured in the liver tissue. The blood estradiol level was higher in females than in males, and the collagen fibril network was denser in males than in females at 8 weeks of age. Estradiol administration in males induced decreases in the HSC area and collagen content of the liver. Conversely, tamoxifen administration in females induced an increase in the HSC area but did not facilitate collagen synthesis. Based on these results, estradiol inhibits the area and collagen synthesis of HSCs in the growing chicken liver under normal physiological conditions. © 2017 Japanese Society of Animal Science.

  4. Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.

    Science.gov (United States)

    Ackerman, Jessica E; Geary, Michael B; Orner, Caitlin A; Bawany, Fatima; Loiselle, Alayna E

    2017-01-01

    Type II Diabetes (T2DM) dramatically impairs the tendon healing response, resulting in decreased collagen organization and mechanics relative to non-diabetic tendons. Despite this burden, there remains a paucity of information regarding the mechanisms that govern impaired healing of diabetic tendons. Mice were placed on either a high fat diet (T2DM) or low fat diet (lean) and underwent flexor tendon transection and repair surgery. Healing was assessed via mechanical testing, histology and changes in gene expression associated with collagen synthesis, matrix remodeling, and macrophage polarization. Obese/diabetic tendons healed with increased scar formation and impaired mechanical properties. Consistent with this, prolonged and excess expression of extracellular matrix (ECM) components were observed in obese/T2DM tendons. Macrophages are involved in both inflammatory and matrix deposition processes during healing. Obese/T2DM tendons healed with increased expression of markers of pro-inflammatory M1 macrophages, and elevated and prolonged expression of M2 macrophages markers that are involved in ECM deposition. Here we demonstrate that tendons from obese/diabetic mice heal with increased scar formation and increased M2 polarization, identifying excess M2 macrophage activity and matrix synthesis as a potential mechanism of the fibrotic healing phenotype observed in T2DM tendons, and as such a potential target to improve tendon healing in T2DM.

  5. Hydrocortisone regulates types I and III collagen gene expression and collagen synthesis in human marrow stromal cells.

    Science.gov (United States)

    Fernández, M; Minguell, J J

    1997-01-01

    Hematopoiesis is the resultant of the orderly molecular and cellular interactions between progenitor cells and stroma. In vitro studies (Dexter-type cultures) have shown that initiation of hematopoiesis only occurs after establishment of a hydrocortisone-dependent layer of stromal cells. Although the molecular basis for the requirement of hydrocortisone are not well understood, data have shown that synthesis/assembly of extracellular matrix molecules (proteoglycans and fibronectin) is regulated by hydrocortisone. Since interstitial collagens are abundantly expressed in the marrow stroma, we investigated whether hydrocortisone may also modulate the expression of collagen types I and III. For these studies, human bone marrow fibroblast cultures were grown in standard culture medium either in the absence or presence of 10(-7) M hydrocortisone. Under both conditions, bone marrow fibroblasts synthesized collagen types I and III, and expressed the respective genes. However, hydrocortisone produced a decrease in the synthesis of interstitial collagens and also in the relative abundance of pro-alpha 1(I) and pro-alpha 1(III) mRNAs. The results of this study are consistent with the assumption that glucocorticoids regulate the expression of several extracellular matrix molecules in the marrow stroma and thus permit in vitro hematopoiesis to occur.

  6. Progress towards discovery of antifibrotic drugs targeting synthesis of type I collagen

    KAUST Repository

    Fritz, Dillon Jeffery

    2011-08-01

    Type I collagen is the most abundant protein in human body. Fibrosis is characterized by excessive synthesis of type I collagen in parenchymal organs. It is a leading cause of morbidity and mortality worldwide, about 45% of all natural deaths are attributable to some fibroproliferative disease. There is no cure for fibrosis. To find specific antifibrotic therapy targeting type I collagen, critical molecular interactions regulating its synthesis must be elucidated. Type I and type III collagen mRNAs have a unique sequence element at the 5\\' end, the 5\\' stem-loop. This stem-loop is not found in any other mRNA. We cloned LARP6 as the protein which binds collagen 5\\' stem-loop with high affinity and specificity. Mutation of the 5\\' stem-loop or knock down of LARP6 greatly diminishes collagen expression. Mice with mutation of the 5\\' stem-loop are resistant to development of liver fibrosis. LARP6 associates collagen mRNAs with filaments composed of nonmuscle myosin; disruption of these filaments abolishes synthesis of type I collagen. Thus, LARP6 dependent collagen synthesis is the specific mechanism of high collagen expression seen in fibrosis. We developed fluorescence polarization (FP) method to screen for drugs that can inhibit binding of LARP6 to 5\\' stem-loop RNA. FP is high when LARP6 is bound, but decreases to low levels when the binding is competed out. Thus, by measuring decrease in FP it is possible to identify chemical compounds that can dissociate LARP6 from the 5\\' stem-loop. The method is simple, fast and suitable for high throughput screening. © 2011 Bentham Science Publishers Ltd.

  7. Asiaticoside induces cell proliferation and collagen synthesis in human dermal fibroblasts

    Directory of Open Access Journals (Sweden)

    Linda Yulianti

    2015-08-01

    Full Text Available Asiatiocoside, a saponin component isolated from Centella asiatica can improve wound healing by promoting the proliferation of human dermal fibroblasts (HDF and synthesis of collagen. The skin-renewing cells and type I and III collagen synthesis decrease with aging, resulting in the reduction of skin elasticity and delayed wound healing. Usage of natural active compounds from plants in wound healing should be evaluated and compared to retinoic acid as an active agent that regulates wound healing. The aim of this study was to compare and evaluate the effect of asiaticoside and retinoic acid to induce greater cell proliferation and type I and III collagen synthesis in human dermal fibroblast. Methods Laboratory experiments were conducted using human dermal fibroblasts (HDF isolated from human foreskin explants. Seven passages of HDF were treated with asiaticoside and retinoic acid at several doses and incubated for 24 and 48 hours. Cell viability in all groups was tested with the MTT assay to assess HDF proliferation. Type I and III collagen synthesis was examined using the respective ELISA kits. Analysis of variance was performed to compare the treatment groups. Results Asiaticoside had significantly stronger effects on HDF proliferation than retinoic acid (p<0.05. The type III collagen production was significantly greater induction with asiaticoside compared to retinoic acid (p<0.05. Conclusion Asiaticoside induces HDF proliferation and type I and III collagen synthesis in a time- and dose-dependent pattern. Asiaticoside has a similar effect as retinoic acid on type I and type III collagen synthesis.

  8. A novel fabrication method to create a thick collagen bundle composed of uniaxially aligned fibrils: an essential technology for the development of artificial tendon/ligament matrices.

    Science.gov (United States)

    Yunoki, Shunji; Hatayama, Hirosuke; Ebisawa, Mizue; Kondo, Eiji; Yasuda, Kazunori

    2015-09-01

    In this study, we developed a fabrication method for thick collagen gel bundles comprising uniaxially aligned fibrils of sufficient size for filling defects in ligament tissues. The fabrication involved rotary shearing to dense collagen sols using a rheometer and then warming them from 23°C to 37°C to trigger gelation upon rotation. Gelation due to collagen fibril formation was accelerated by increased concentrations of neutral phosphate buffer, and fibril alignment occurred within 20 s during the early stage of rapid gelation. Fabrication of gels was completed with slippage between gels and the movable upper plate, and well-aligned fibrils along the rotation direction were observed in the marginal regions of disc-shaped gels. Gel thickness could be increased from 1 to 3 mm with homogeneous alignment of fibrils in the entire sample. The alignment of fibrils improved mechanical properties against tensile loads that were placed parallel to the alignment axis. Elongation of cultured fibroblast along the alignment was observed on the gels. The present method will enable the bottom-up fabrication of an artificial tendon for ligament reconstruction and repair. © 2015 Wiley Periodicals, Inc.

  9. Intrinsic flexor-tendon repair. A morphological study in vitro.

    Science.gov (United States)

    Manske, P R; Gelberman, R H; Vande Berg, J S; Lesker, P A

    1984-03-01

    Rabbit flexor tendons with a 90 per cent mid-section transverse laceration demonstrated the intrinsic capacity to participate in the repair process in the absence of extrinsic cell sources and without the benefit of nutrition from a circulating blood supply or the influence of synovial fluid. Two cellular processes were involved in the in vitro repair process: (1) phagocytosis occurred by differentiation of fibroblasts from the epitenon--the cells migrated into the repair site and removed cellular debris and collagen fragments, and (2) collagen synthesis occurred primarily within the endotenon cells. The results of this experimental study support the concept that flexor tendons have the intrinsic capacity to phagocytize old collagen and synthesize new collagen fibrils. Consequently, clinical attempts to prevent or control the peripheral adhesions appear valid, since these adhesions do not appear to be an essential component of the repair process.

  10. FISH SKIN ISOLATED COLLAGEN CRYOGELS FOR TISSUE ENGINEERING APPLICATIONS: PURIFICATION, SYNTHESIS AND CHARACTERIZATION

    Directory of Open Access Journals (Sweden)

    Nimet Bölgen

    2016-09-01

    Full Text Available Tissue engineering aims regenerating damaged tissues by using porous scaffolds, cells and bioactive agents. The scaffolds are produced from a variety of natural and synthetic polymers. Collagen is a natural polymer widely used for scaffold production in the late years because of its being the most important component of the connective tissue and biocompatibility. Cryogelation is a relatively simple technique compared to other scaffold production methods, which enables to produce interconnected porous matrices from the frozen reaction mixtures of polymers or monomeric precursors. Considering these, collagen was isolated in this study from fish skin which is a non-commercial waste material, and scaffolds were produced from this collagen by cryogelation method. By SEM analysis, porous structure of collagen, and by UV-Vis analysis protein structure was proven, and by Zeta potential iso-electrical point of the protein was determined, and,  Amit A, Amit B, Amit I, Amit II and Amit III characteristical peaks were demonstrated by FTIR analysis. The collagen isolation yield was, 14.53% for acid soluble collagen and 2.42% for pepcin soluble collagen. Scaffolds were produced by crosslinking isolated acid soluble collagen with glutaraldehyde at cryogenic conditions. With FTIR analysis, C=N bond belonging to gluteraldehyde reaction with collagen was found to be at 1655 cm-1. It was demonstrated by SEM analysis that collagen and glutaraldeyhde concentration had significant effects on the pore morphology, diameter and wall thickness of the cryogels, which in turned changed the swelling ratio and degradation profiles of the matrices. In this study, synthesis and characterization results of a fish skin isolated collagen cryogel scaffold that may be potentially used in the regeneration of damaged tissues are presented.

  11. Leucine-Enriched Essential Amino Acids Augment Mixed Protein Synthesis, But Not Collagen Protein Synthesis, in Rat Skeletal Muscle after Downhill Running

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kato

    2016-06-01

    Full Text Available Mixed and collagen protein synthesis is elevated for as many as 3 days following exercise. Immediately after exercise, enhanced amino acid availability increases synthesis of mixed muscle protein, but not muscle collagen protein. However, the potential for synergic effects of amino acid ingestion with exercise on both mixed and collagen protein synthesis remains unclear. We investigated muscle collagen protein synthesis in rats following post-exercise ingestion of leucine-enriched essential amino acids. We determined fractional protein synthesis rates (FSR at different time points following exercise. Mixed protein and collagen protein FSRs in skeletal muscle were determined by measuring protein-bound enrichments of hydroxyproline and proline, and by measuring the intracellular enrichment of proline, using injections of flooding d3-proline doses. A leucine-enriched mixture of essential amino acids (or distilled water as a control was administrated 30 min or 1 day post-exercise. The collagen protein synthesis in the vastus lateralis was elevated for 2 days after exercise. Although amino acid administration did not increase muscle collagen protein synthesis, it did lead to augmented mixed muscle protein synthesis 1 day following exercise. Thus, contrary to the regulation of mixed muscle protein synthesis, muscle collagen protein synthesis is not affected by amino acid availability after damage-inducing exercise.

  12. Evaluating the utility of circulating biomarkers of collagen synthesis in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ellims, Andris H; Taylor, Andrew J; Mariani, Justin A; Ling, Liang-Han; Iles, Leah M; Maeder, Micha T; Kaye, David M

    2014-03-01

    In hypertrophic cardiomyopathy (HCM), accumulation of myocardial collagen may play a central role in the pathogenesis of diastolic dysfunction and arrhythmia. Previous studies have suggested that peripheral levels of byproducts of collagen synthesis are reflective of myocardial extracellular matrix metabolism, although this has not been validated in detail. Given the potential clinical utility of such biomarkers, we sought to validate the assumed relationship between peripheral markers and myocardial fibrosis in HCM. Fifty patients with HCM and 25 healthy controls underwent peripheral venous sampling to determine plasma concentrations of key collagen precursors (procollagen I and III N-terminal propeptides [PINP, PIIINP]). Contrast-enhanced cardiac magnetic resonance imaging was performed to quantify regional (by late-gadolinium enhancement) and diffuse (by T1 mapping) myocardial fibrosis. Nineteen subjects also underwent simultaneous arterial and coronary sinus blood sampling (to derive transcardiac concentration gradients of PINP, PIIINP, and C-terminal telopeptide of type I collagen) and right heart catheterization. Despite cardiac magnetic resonance evidence of regional (late-gadolinium enhancement quantity, 6.4±8.0%) and diffuse (T1 time, 478±79 ms) myocardial fibrosis in patients with HCM, peripheral levels of collagen precursors were similar compared with control subjects (PINP, 45.9±22.9 versus 53.4±25.9 μg/L; P=0.21; PIIINP, 4.8±1.7 versus 4.4±1.1 μg/L; P=0.26). No significant net positive transcardiac concentration gradient was detected for either biomarker of collagen synthesis. The cardiac contribution to peripheral levels of byproducts of collagen synthesis in patients with HCM is insignificant. Furthermore, peripheral levels of these biomarkers do not accurately reflect myocardial collagen content in these patients.

  13. FIBRILLINS IN TENDON

    Directory of Open Access Journals (Sweden)

    Betti Giusti

    2016-10-01

    Full Text Available Tendons among connective tissue, mainly collagen, contain also elastic fibres made of fibrillin 1, fibrillin 2 and elastin that are broadly distributed in tendons and represent 1-2% of the dried mass of the tendon. Only in the last years, studies on structure and function of elastic fibres in tendons have been performed. Aim of this review is to revise data on the organization of elastic fibres in tendons, in particular fibrillin structure and function, and on the clinical manifestations associated to alterations of elastic fibres in tendons. Indeed, microfibrils may contribute to tendon mechanics; therefore, their alterations may cause joint hypermobility and contractures which have been found to be clinical features in patients with Marfan syndrome and Beals syndrome. The two diseases are caused by mutations in genes FBN1 and FBN2 encoding fibrillin 1 and fibrillin 2, respectively.

  14. Tendinosis-like histologic and molecular changes of the Achilles tendon to repetitive stress: a pilot study in rats.

    Science.gov (United States)

    Cho, Nam Soon; Hwang, Ji Hye; Lee, Yong Taek; Chae, Seoung Wan

    2011-11-01

    Tendinopathy (pain and tendon degeneration) is associated with repetitive use and mechanical overload. However, the etiology of tendinopathy remains unclear. Clarification of histologic and molecular changes of tendon to repetitive stress could provide better understanding of Achilles tendon disorders related to repetitive stress. We asked whether repetitive stress simulating overuse of the Achilles tendon induced (1) histologic changes in rats similar to tendinosis (increased cellularity of fibrocytes, increased disorganization of collagen fiber, and increased roundness of the nucleus of the fibrocyte), (2) increased collagen Type III occurrence, and (3) increased inducible nitric oxide synthase (iNOS) expression. We used an exercise protocol simulating repetitive, jerky, eccentric contraction of the triceps surae in 15 rats. We conducted the exercise for 2 hours per day, three times per week using the right rear legs only and the left legs as internal controls. We harvested Achilles tendons after either 2, 4, or 6 weeks of exercise, and evaluated changes in tendon thickness, fibrocyte count, collagen fiber arrangement, collagen fiber type, and occurrence of iNOS. Exercised Achilles tendons showed increased cellularity of fibrocytes at 4 and 6 weeks of exercise, and disorganized collagen fiber arrangement at 6 weeks of exercise. There was a trend for Type III collagen occurrence being greater in experimental groups. Expression of iNOS increased after 2 and 4 weeks of exercise when compared with that of the controls, but decreased after 6 weeks. These observations suggest repetitive, synchronized, passive, and jerky exercise induced by electrical stimulation can lead to the tendinosis-like changes in the Achilles tendons in rats with imbalance between synthesis and degeneration after 4 weeks of exercise. This newly designed exercise protocol may be used to design an animal model of Achilles tendon overuse. With this model, therapeutic interventions of tendinopathy

  15. Type I collagen synthesis parallels the conversion of keratinocytic intraepidermal neoplasia to cutaneous squamous cell carcinoma.

    Science.gov (United States)

    van Kempen, Léon C L T; Rijntjes, Jos; Claes, An; Blokx, Willeke A M; Gerritsen, Marie-Jeanne P; Ruiter, Dirk J; van Muijen, Goos N P

    2004-11-01

    Neoplastic progression of solid tumours is often characterized by a simultaneous increase in matrix protein (eg collagen) synthesis and degradation, and results in the formation of a tumour stroma. At the tumour periphery, this process is believed to facilitate angiogenesis and invasive growth of tumour cells. In various types of carcinoma, differentiation of fibroblasts towards myofibroblasts is thought to play an important role in extracellular matrix remodelling as their emergence coincides with architectural changes in the tumour stroma. Here, distinct architectural changes in collagen fibres are reported in cutaneous squamous cell carcinomas (cSCC) with respect to normal skin and precursor lesions, ie keratinocytic intraepidermal neoplasia (KIN). Simultaneously, type I collagen mRNA was observed in fibroblasts in close proximity to cSCC lesions (19/19) but only in 2 of 10 KIN lesions tested. Interestingly, whereas emerging of myofibroblasts correlated with reduced differentiation of cSCCs, it was not a prerequisite for type I collagen synthesis. These data indicate that type I collagen synthesis by fibroblasts parallels the malignant transformation of human KIN to cSCC. Copyright (c) 2004 Pathological Society of Great Britain and Ireland.

  16. Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

    Directory of Open Access Journals (Sweden)

    Fanglong Song

    2017-02-01

    Full Text Available Background/Aims: This study investigated the effect of mechanical stress on tendon-bone healing in a rabbit anterior cruciate ligament (ACL reconstruction model as well as cell proliferation and matrix formation in co-culture of bone-marrow mesenchymal stem cells (BMSCs and tendon cells (TCs. Methods: The effect of continuous passive motion (CPM therapy on tendon-bone healing in a rabbit ACL reconstruction model was evaluated by histological analysis, biomechanical testing and gene expressions at the tendon-bone interface. Furthermore, the effect of mechanical stretch on cell proliferation and matrix synthesis in BMSC/TC co-culture was also examined. Results: Postoperative CPM therapy significantly enhanced tendon-bone healing, as evidenced by increased amount of fibrocartilage, elevated ultimate load to failure levels, and up-regulated gene expressions of Collagen I, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin at the tendon-bone junction. In addition, BMSC/TC co-culture treated with mechanical stretch showed a higher rate of cell proliferation and enhanced expressions of Collagen I, Collagen III, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin than that of controls. Conclusion: These results demonstrated that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation, which results in enhanced regenerative potential of BMSCs and TCs in tendon-bone healing.

  17. Characterization of type I collagen synthesis and maturation in uterine carcinosarcomas.

    Science.gov (United States)

    Kauppila, S; Stenbäck, F; Kacinski, B M; Carcangiu, M L; Risteli, J; Risteli, L

    1999-10-01

    Epithelial malignancies often induce an enhanced expression of interstitial collagens in the fibroblasts within the tumor tissue and the surrounding non-neoplastic stroma. In uterine carcinosarcomas (malignant mixed müllerian tumors [MMMTs]) both the stroma and the epithelium are malignant. In this investigation, both in situ hybridization and immunohistochemical staining were applied with two different antibodies that were capable of distinguishing between newly synthesized and mature, trivalently cross-linked Type I collagen to define Type I procollagen mRNA expression and the synthesis and maturation of the corresponding protein in MMMTs. In the better differentiated parts of these tumors, in which anticytokeratins stained only clearly carcinomatous cells, Type I procollagen mRNA expression was limited to stromal fibroblasts; mature Type I collagen bundles were abundant and regular. In poorly differentiated areas, in which anticytokeratins stained only a few individual cells, Type I procollagen mRNA was expressed peculiarly by three morphologically different cell types. In addition to benign mesenchymal cells, Type I procollagen mRNA was present in atypical epithelial and mesenchymal cells. In these tumors, the collagen bundles close to the malignant cells were comprised of newly synthesized Type I collagen, with only little evidence of the presence of mature, fully cross-linked collagen. These results strongly suggest that the undifferentiated cells of MMMTs are capable of producing their own stroma with irregularly arranged collagen bundles. Copyright 1999 American Cancer Society.

  18. Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue.

    Science.gov (United States)

    Papachroni, Katerina K; Piperi, Christina; Levidou, Georgia; Korkolopoulou, Penelope; Pawelczyk, Leszek; Diamanti-Kandarakis, Evanthia; Papavassiliou, Athanasios G

    2010-10-01

    Connective tissue components--collagen types I, III and IV--surrounding the ovarian follicles undergo drastic changes during ovulation. Abnormal collagen synthesis and increased volume and density of ovarian stroma characterize the polycystic ovary syndrome (PCOS). During the ovulatory process, collagen synthesis is regulated by prolyl hydroxylase and lysyl oxidase (LOX) activity in ovarian follicles. LOX catalyzes collagen and elastin cross-linking and plays essential role in coordinating the control of ovarian extracellular matrix (ECM) during follicular development. We have recently shown accumulation of advanced glycation end products (AGEs), molecules that stimulate ECM production and abnormal collagen cross-linking, in ovarian tissue. However, the possible link between LOX and AGEs-induced signalling in collagen production and stroma formation in ovarian tissue from PCOS remains elusive. The present study investigates the hypothesis of AGE signalling pathway interaction with LOX gene activity in polycystic ovarian (PCO) tissue. We show an increased distribution and co-localization of LOX, collagen type IV and AGE molecules in the PCO tissue compared to control, as well as augmented expression of AGE signalling mediators/effectors, phospho(p)-ERK, phospho(p)-c-Jun and nuclear factor κB (NF-κB) in pathological tissue. Moreover, we demonstrate binding of AGE-induced transcription factors, NF-κB and activator protein-1 (AP-1) on LOX promoter, indicating a possible involvement of AGEs in LOX gene regulation, which may account for the documented increase in LOX mRNA and protein levels compared to control. These findings suggest that deposition of excess collagen in PCO tissue that induces cystogenesis may, in part, be due to AGE-mediated stimulation of LOX activity. © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  19. Tendon and ligament imaging

    Science.gov (United States)

    Hodgson, R J; O'Connor, P J; Grainger, A J

    2012-01-01

    MRI and ultrasound are now widely used for the assessment of tendon and ligament abnormalities. Healthy tendons and ligaments contain high levels of collagen with a structured orientation, which gives rise to their characteristic normal imaging appearances as well as causing particular imaging artefacts. Changes to ligaments and tendons as a result of disease and injury can be demonstrated using both ultrasound and MRI. These have been validated against surgical and histological findings. Novel imaging techniques are being developed that may improve the ability of MRI and ultrasound to assess tendon and ligament disease. PMID:22553301

  20. Type I collagen synthesis parallels the conversion of keratinocytic intraepidermal neoplasia to cutaneous squamous cell carcinoma.

    NARCIS (Netherlands)

    Kempen, L.C.L.T. van; Rijntjes, J.; Claes, A.; Blokx, W.A.M.; Gerritsen, M.J.P.; Ruiter, D.J.; Muijen, G.N.P. van

    2004-01-01

    Neoplastic progression of solid tumours is often characterized by a simultaneous increase in matrix protein (eg collagen) synthesis and degradation, and results in the formation of a tumour stroma. At the tumour periphery, this process is believed to facilitate angiogenesis and invasive growth of

  1. Photobiomodulation on the proliferation and collagen synthesis of normal human skin fibroblast cells

    Science.gov (United States)

    Cheng, Lei; Liu, Timon Cheng-Yi; Chi, Jin-Quan; Li, Yan; Jin, Hua

    2006-01-01

    Background and Objective: Cultured normal human skin fibroblast cells (HSFs) were once used to study the mechanism of the effects of low intensity He-Ne laser irradiation (LHNL) on wound healing. The proliferation and collagen synthesis of HFSs were modulated by LHNL in different papers, respectively, and both of them are studied in this paper. Study Design/Materials and Methods: The dosage was studied for the same radiation time 300s. The proliferation and collagen synthesis were measured by 3-[4,5-Dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay and the spectrophotometric method for the determination of hydroxyproline, respectively. Results: The dose zones were called dose 1, dose 2 and dose 3 from low dose on so that HSF proliferation was inhibited in dose 1 (16, 24 mJ/cm2), and promoted in dose 2 (298, 503, 597mJ/cm2), and the collagen synthesis was inhibited in dose 2 (401, 526 mJ/cm2), and promoted in dose 3 (714, 926, 1539, 1727mJ/cm2), which supports our biological model of photobiomodulation. It was found there is the linear relationship of the effect with dose with dose in each dose zone. Conclusions: The photobiomodulation on the proliferation and collagen synthesis of HSFs might be linearly dose-dependent in limited dosage with radiation time kept constant, which provides a foundation to discuss photobiomodulation on wound healing.

  2. Adrenomedullin and adrenotensin regulate collagen synthesis and proliferation in pulmonary arterial smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, W. [School of Control Science and Engineering, Biomedical Engineering Institute, Shandong University, Jinan, Shandong (China); Kong, Q.Y.; Zhao, C.F. [Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong (China); Zhao, F. [Department of Medicine, Weill Medical College of Cornell University, New York, NY (United States); Li, F.H.; Xia, W. [Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong (China); Wang, R. [Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong (China); Hu, Y.M. [School of Control Science and Engineering, Biomedical Engineering Institute, Shandong University, Jinan, Shandong (China); Hua, M. [Shandong Institute of Scientific and Technical Information, Jinan, Shandong (China)

    2013-12-10

    To understand the pathophysiological mechanisms of pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular-matrix accumulation in the development of pulmonary hypertension and remodeling, this study determined the effects of different doses of adrenomedullin (ADM) and adrenotensin (ADT) on PASMC proliferation and collagen synthesis. The objective was to investigate whether extracellular signal-regulated kinase (ERK1/2) signaling was involved in ADM- and ADT-stimulated proliferation of PASMCs in 4-week-old male Wistar rats (body weight: 100-150 g, n=10). The proliferation of PASMCs was examined by 5-bromo-2-deoxyuridine incorporation. A cell growth curve was generated by the Cell Counting Kit-8 method. Expression of collagen I, collagen III, and phosphorylated ERK1/2 (p-ERK1/2) was evaluated by immunofluorescence. The effects of different concentrations of ADM and ADT on collagen I, collagen III, and p-ERK1/2 protein expression were determined by immunoblotting. We also investigated the effect of PD98059 inhibition on the expression of p-ERK1/2 protein by immunoblotting. ADM dose-dependently decreased cell proliferation, whereas ADT dose-dependently increased it; and ADM and ADT inhibited each other with respect to their effects on the proliferation of PASMCs. Consistent with these results, the expression of collagen I, collagen III, and p-ERK1/2 in rat PASMCs decreased after exposure to ADM but was upregulated after exposure to ADT. PD98059 significantly inhibited the downregulation by ADM and the upregulation by ADT of p-ERK1/2 expression. We conclude that ADM inhibited, and ADT stimulated, ERK1/2 signaling in rat PASMCs to regulate cell proliferation and collagen expression.

  3. Role of tissue engineered collagen based tridimensional implant on the healing response of the experimentally induced large Achilles tendon defect model in rabbits: a long term study with high clinical relevance

    Science.gov (United States)

    2013-01-01

    Background Tendon injury is one of the orthopedic conditions poses with a significant clinical challenge to both the surgeons and patients. The major limitations to manage these injuries are poor healing response and development of peritendinous adhesions in the injured area. This study investigated the effectiveness of a novel collagen implant on tendon healing in rabbits. Results Seventy five mature White New-Zealand rabbits were divided into treated (n = 55) and control (n = 20) groups. The left Achilles tendon was completely transected and 2 cm excised. The defects of the treated animals were filled with collagen implants and repaired with sutures, but in control rabbits the defects were sutured similarly but the gap was left untreated. Changes in the injured and normal contralateral tendons were assessed weekly by measuring the diameter, temperature and bioelectrical characteristics of the injured area. Clinical examination was done and scored. Among the treated animals, small pilot groups were euthanized at 5, 10, 15, 20, 30, 40 and 60 (n = 5 at each time interval) and the remainder (n = 20) and the control animals at 120 days post injury (DPI). The lesions of all animals were examined at macroscopic and microscopic levels and the dry matter content, water delivery and water uptake characteristics of the lesions and normal contralateral tendons of both groups were analyzed at 120 DPI. No sign of rejection was seen in the treated lesions. The collagen implant was invaded by the inflammatory cells at the inflammatory phase, followed by fibroplasia phase in which remnant of the collagen implant were still present while no inflammatory reaction could be seen in the lesions. However, the collagen implant was completely absorbed in the remodeling phase and the newly regenerated tendinous tissue filled the gap. Compared to the controls, the treated lesions showed improved tissue alignment and less peritendinous adhesion, muscle atrophy and fibrosis

  4. Structural and biochemical alterations during the healing process of tendons treated with Aloe vera.

    Science.gov (United States)

    Aro, A A; Nishan, U; Perez, M O; Rodrigues, R A; Foglio, M A; Carvalho, J E; Gomes, L; Vidal, B C; Pimentel, E R

    2012-10-29

    The tendon is composed of highly organized collagen fibers that form a complex supramolecular structure. After lesions, the organization and composition of the tendon are not completely restored. Our purpose was to evaluate if the application of Aloe vera improves tendon healing, considering the effectiveness in the stimulus of collagen synthesis. The calcaneal tendon of male Wistar rats was partially transected with subsequent topical application of A. vera ointment at the injury. The animals were separated into groups with tendons treated with the A. vera extract for 7days and excised on the 7th, 14th and 21st days after surgery; control rats received only ointment base without plant extract. Morphological analysis using polarization microscopy showed that the entire tendon undergoes a remodeling process, with disorganized collagen fibers by days 7 and 14 in plant-treated and non-treated groups and with a higher birefringence in tendons of the plant-treated group on the 21st day. A higher concentration of hydroxyproline was found in plant-treated tendons on days 7 and 14 compared with their controls. Western blots showed lower amounts of type I collagen in the plant-treated group on day 14 compared with the control. MMP-9 diminished 14days after lesion and the active isoform of MMP-2 increased on day 21 in plant-treated groups. The present study indicates a beneficial effect of A. vera in the tissue reorganization in the transected region of the tendon 21days after injury and is supported by an increase of active MMP-2. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Immobilization of Lipases on Magnetic Collagen Fibers and Its Applications for Short-Chain Ester Synthesis

    Directory of Open Access Journals (Sweden)

    Shengsheng He

    2017-06-01

    Full Text Available Magnetic nanoparticles (MNp Fe3O4 were prepared by chemical coprecipitation, and introduced onto collagen fibers to form magnetic collagen support (MNp-Col for enzyme immobilization. Candida rugosa lipase has been successfully immobilized on MNp-Col supports by a covalent bond cross-linking agent, glutaraldehyde. The characteristics of MNp-Col and the immobilized lipase were investigated. The immobilized lipase displayed sound magnetic separation abilities in both aqueous and organic media. The activity of the immobilized lipase reached 2390 U/g under optimal conditions. The MNp-Col immobilized lipase shows broadened temperature and pH ranges for hydrolysis of olive oil emulsion. For synthesis of butyrate esters in an n-hexane medium, the yield changes through use of different alcohols, among which, butyric butyrate showed the highest yield. The prepared magnetic collagen fiber provides separation support for enzyme immobilization and has the potential to be used in other biotechnology fields.

  6. Silver nanoparticles alter proteoglycan expression in the promotion of tendon repair.

    Science.gov (United States)

    Kwan, Karen H L; Yeung, Kelvin W K; Liu, Xuelai; Wong, Kenneth K Y; Shum, Ho Cheung; Lam, Yun Wah; Cheng, Shuk Han; Cheung, Kenneth M C; To, Michael K T

    2014-10-01

    This study demonstrates a novel method of using silver nanoparticles for Achilles tendon injury healing. In vitro results indicated a stimulatory effect on cell proliferation and collagen synthesis with silver nanoparticles. Biomechanical test on the 42-day post operation Achilles tendon sample exhibited a significant improvement in tensile modulus when compared to the untreated group. Histology suggested that silver nanoparticles promoted cell alignment and proteoglycan synthesis. The collagen deposition was also improved. An alleviation of tumor necrosis factor α, and an increase in fibromodulin and proliferating cell nuclear antigen expression were seen in silver nanoparticles group by immunohistochemistry. This study further corroborates the finding of our previous study that silver nanoparticles help to restore the functionality of injured connective tissues. We believe that the anti-inflammatory nature of silver nanoparticles has an important role in accelerating the healing process and reducing scarring, leading to better functional outcome. From the clinical editor: Tendon healing after surgeries remains a slow and tedious process, typically requiring several weeks of recovery time and gradual introduction of physical therapy. There are no currently utilized methods that could promote tendon healing. In this study, silver nanoparticles are reported to facilitate Achilles tendon repair in a model system, through increased proteoglycan and collagen synthesis, paving the way to potential clinical applications in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Collagen type I, III and V differently modulate synthesis and activation of matrix metalloproteinases by cultured rabbit periosteal fibroblasts

    NARCIS (Netherlands)

    Kerkvliet, Erica H. M.; Jansen, Ineke C.; Schoenmaker, Ton; Beertsen, Wouter; Everts, Vincent

    2003-01-01

    In the present study we investigated whether the collagen types I, III and V affect the activity of fibroblasts obtained from rabbit periosteum. The cells were cultured on plates either or not coated with different amounts of collagen type I, III or V and analyzed for their attachment, DNA synthesis

  8. Sumoylation of the Tumor Suppressor Promyelocytic Leukemia Protein Regulates Arsenic Trioxide-Induced Collagen Synthesis in Osteoblasts

    Directory of Open Access Journals (Sweden)

    Wen-Xiao Xu

    2015-11-01

    Full Text Available Background/Aims: Promyelocytic leukemia (PML protein is a tumor suppressor that fuses with retinoic acid receptor-α (PML-RARα to contribute to the initiation of acute promyelocytic leukemia (APL. Arsenic trioxide (ATO upregulates expression of TGF-β1, promoting collagen synthesis in osteoblasts, and ATO binds directly to PML to induce oligomerization, sumoylation, and ubiquitination. However, how ATO upregulates TGF-β1 expression is uncertain. Thus, we suggested that PML sumoylation is responsible for regulation of TGF-β1 protein expression. Methods: Kunming mice were treated with ATO, and osteoblasts were counted under scanning electron microscopy. Masson's staining was used to quantify collagen content. hFOB1.19 cells were transfected with siRNA against UBC9 or RNF4, and then treated with ATO or FBS. TGF-β1, PML expression, and sumoylation were quantified with Western blot, and collagen quantified via immunocytochemistry. Results: ATO enhanced osteoblast accumulation, collagen synthesis, and PML-NB formation in vivo. Knocking down UBC9 in hFOB1.19 cells inhibited ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conversely, knocking down RNF4 enhanced ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conclusion: These data suggest that PML sumoylation is required for ATO-induced collagen synthesis in osteoblasts.

  9. Collagen synthesis in postmenopausal women during therapy with anabolic steroid or female sex hormones

    DEFF Research Database (Denmark)

    Hassager, C; Jensen, L T; Pødenphant, J

    1990-01-01

    The effect of anabolic steroid therapy and estrogen-progestogen substitution therapy on serum concentration of procollagen type III aminoterminal peptide (PIIINP), a measure of collagen synthesis, in postmenopausal women was studied in two double-blind studies: (1) 39 women allocated to treatment...... the study. Anabolic steroid therapy resulted in a more than 50% increase (P less than .001) in serum PIIINP at 3 months, which thereafter decayed but remained significantly increased throughout the study period. Serum PIIINP showed the same pattern during estrogen-progestogen therapy, but to a lesser degree....... We conclude that anabolic steroids stimulate type III collagen synthesis in postmenopausal women, while estrogen-progestogen therapy may have such an effect, but only to a lesser degree....

  10. Ascorbyl coumarates as multifunctional cosmeceutical agents that inhibit melanogenesis and enhance collagen synthesis.

    Science.gov (United States)

    Kwak, Jun Yup; Park, Soojin; Seok, Jin Kyung; Liu, Kwang-Hyeon; Boo, Yong Chool

    2015-09-01

    L-Ascorbic acid (AA) and p-coumaric acid (p-CA) are naturally occurring antioxidants that are known to enhance collagen synthesis and inhibit melanin synthesis, respectively. The purpose of this study was to examine hybrid compounds between AA and p-CA as multifunctional cosmeceutical agents. Ascorbyl 3-p-coumarate (A-3-p-C), ascorbyl 2-p-coumarate (A-2-p-C), and their parent compounds were tested for their effects on cellular melanin synthesis and collagen synthesis. At 100 μM, A-3-p-C and A-2-p-C decreased melanin content of human dermal melanocytes stimulated by L-tyrosine, by 65 and 59%, respectively, compared to 11% inhibition of AA and 70% inhibition of p-CA. A-3-p-C and A-2-p-C were less effective than p-CA but more effective than AA at inhibiting tyrosinase activity. A-3-p-C and A-2-p-C were more effective than p-CA at inhibiting the autoxidation of L-3,4-dihydroxyphenylalanine. At 100-300 μM, A-3-p-C and A-2-p-C augmented collagen release from human dermal fibroblasts by 120-144% and 125-191%, respectively, compared to 126-133% increase of AA and 120-146% increase of p-CA. They increased procollagen type I C-peptide release (A-3-p-C, and A-2-p-C) like AA, and decreased matrix metalloproteinase 1 level (A-2-p-C) like p-CA, implicating that they might regulate collagen metabolism by multiple mechanisms. This study suggests that A-3-p-C and A-2-p-C could be used as multifunctional cosmeceutical agents for the attenuation of certain aspects of skin aging.

  11. Collagen-chitosan scaffold modified with Au and Ag nanoparticles: Synthesis and structure

    Energy Technology Data Exchange (ETDEWEB)

    Rubina, M.S.; Kamitov, E.E. [A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, 119991 Russian Federation (Russian Federation); Zubavichus, Ya. V.; Peters, G.S. [National Research center «Kurchatov Institute», Moscow, 123182 Russian Federation (Russian Federation); Naumkin, A.V. [A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, 119991 Russian Federation (Russian Federation); Suzer, S. [Department of Chemistry, Bilkent University, Ankara, 06800 Turkey (Turkey); Vasil’kov, A.Yu., E-mail: alexandervasilkov@yandex.ru [A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, 119991 Russian Federation (Russian Federation)

    2016-03-15

    Graphical abstract: - Highlights: • Biocompatible collagen-chitosan scaffolds were modified by Au and Ag nanoparticles via the metal-vapor synthesis. • Structural and morphological parameters of the nanocomposites were assessed using a set of modern instrumental techniques, including electron microscopy, X-ray diffraction, small-angle X-ray scattering, EXAFS, XPS. • Potential application of the nanocomposites are envisaged. - Abstract: Nowadays, the dermal biomimetic scaffolds are widely used in regenerative medicine. Collagen-chitosan scaffold one of these materials possesses antibacterial activity, good compatibility with living tissues and has been already used as a wound-healing material. In this article, collagen-chitosan scaffolds modified with Ag and Au nanoparticles have been synthesized using novel method - the metal-vapor synthesis. The nanocomposite materials are characterized by XPS, TEM, SEM and synchrotron radiation-based X-ray techniques. According to XRD data, the mean size of the nanoparticles (NPs) is 10.5 nm and 20.2 nm in Au-Collagen-Chitosan (Au-CollCh) and Ag-Collagen-Chitosan (Ag-CollCh) scaffolds, respectively in fair agreement with the TEM data. SAXS analysis of the composites reveals an asymmetric size distribution peaked at 10 nm for Au-CollCh and 25 nm for Ag-CollCh indicative of particle's aggregation. According to SEM data, the metal-carrying scaffolds have layered structure and the nanoparticles are rather uniformly distributed on the surface material. XPS data indicate that the metallic nanoparticles are in their unoxidized/neutral states and dominantly stabilized within the chitosan-rich domains.

  12. Transcription factor EGR1 directs tendon differentiation and promotes tendon repair

    National Research Council Canada - National Science Library

    Guerquin, Marie-Justine; Charvet, Benjamin; Nourissat, Geoffroy; Havis, Emmanuelle; Ronsin, Olivier; Bonnin, Marie-Ange; Ruggiu, Mathilde; Olivera-Martinez, Isabel; Robert, Nicolas; Lu, Yinhui; Kadler, Karl E; Baumberger, Tristan; Doursounian, Levon; Berenbaum, Francis; Duprez, Delphine

    2013-01-01

    Tendon formation and repair rely on specific combinations of transcription factors, growth factors, and mechanical parameters that regulate the production and spatial organization of type I collagen...

  13. Plasma platelet-rich autogenous healing tendon of the gastrocnemius muscle in rabbits

    Directory of Open Access Journals (Sweden)

    Duvaldo Eurides

    2015-04-01

    Full Text Available Tendon lesions may involve the partial or total section of the common calcaneal tendon and cause postural changes of the member. This study evaluated, after 45 and 90 postoperative days (PO, the repair of the tendon of gastrocnemius muscle of rabbits with topical application of autologous platelet concentrate. Twelve adult rabbits were divided into two groups (n = 6 undergoing cardiac puncture and collection of 10 ml of blood to obtain platelet rich-plasma (PRP. Animals of both groups had a transverse tenotomy in the middle third of the lateral belly of the gastrocnemius tendon and muscle that was approximated with modified Kessler suture and nylon thread. In the animals of the treated group it was applied the average of 490.644 platelets / uL of PRP, per animal over the tendon synthesis. The treated group showed a higher amount of collagen fibers than the control one, and at 90 PO days the intensity of collagen was higher than at 45 days with more fibroblasts in the control than in treated one. The administration of plasma autogenous platelet concentrate in the repair of the gastrocnemius tendon of rabbits stimulates and organizes the repair process and causes early production of collagen fibers.

  14. Chronic alterations in growth hormone/insulin-like growth factor-I signaling lead to changes in mouse tendon structure

    DEFF Research Database (Denmark)

    Nielsen, R H; Clausen, N M; Schjerling, P

    2014-01-01

    The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis is an important stimulator of collagen synthesis in connective tissue, but the effect of chronically altered GH/IGF-I levels on connective tissue of the muscle-tendon unit is not known. We studied three groups of mice; 1) giant...

  15. How do glucocorticoids compare to oligo decoys as inhibitors of collagen synthesis and potential toxicity of these therapeutics?

    Science.gov (United States)

    Cutroneo, Kenneth R; Sterling, Kenneth M

    2004-05-01

    This article demonstrates how glucocorticoids decrease collagen synthesis. The parameters used to assess procollagen synthesis in our laboratory will be compared to those used by others. This article will note all the pertinent literature on the molecular mechanisms of this down regulation of procollagen synthesis. For example, what are the effects of glucocorticoids at the levels of transcription and translation of collagen mRNAs? Finally, we will define a molecular mechanism to inhibit Type I collagen synthesis by decreasing the binding of the TGF-beta activator protein complex to the TGF-beta element in the distal promoter of the proalpha1 Type I collagen gene, preventing the 2:1 ratio of alpha1 to alpha2 chains in the processed Type I collagen molecule. We will next ask "How do sense oligo decoys decrease Type I collagen synthesis at the in vivo and at the cell levels?" In primary fibrotic cell culture, the double-stranded phosphorothioate oligodeoxynucleotide decoys were more effective than their sense single-stranded counterparts. The molecular mechanism for the decrease in Type I collagen synthesis is the same as glucocorticoids, that is by decreasing the binding of the TGF-beta activator protein complex to the TGF-beta element in the distal promoter of the proalpha1 Type I collagen gene for the transcription of the proalpha1 mRNAs. The reason for using sense oligo decoys as anti-fibrotic agents as compared to the anti-fibrotic glucocorticoids, is that presently marketed and FDA approved glucocorticoids have many untoward side effects which the sense oligo decoys do not have. Copyright 2004 Wiley-Liss, Inc.

  16. Cadherin-11 modulates cell morphology and collagen synthesis in periodontal ligament cells under mechanical stress.

    Science.gov (United States)

    Feng, Lishu; Zhang, Yimei; Kou, Xiaoxing; Yang, Ruili; Liu, Dawei; Wang, Xuedong; Song, Yang; Cao, Haifeng; He, Danqing; Gan, Yehua; Zhou, Yanheng

    2017-03-01

    To examine the role of cadherin-11, an integral membrane adhesion molecule, in periodontal ligament cells (PDLCs) under mechanical stimulation. Human PDLCs were cultured and subjected to mechanical stress. Cadherin-11 expression and cell morphology of PDLCs were investigated via immunofluorescence staining. The mRNA and protein expressions of cadherin-11 and type I collagen (Col-I) of PDLCs were evaluated by quantitative real-time polymerase chain reaction and Western blot, respectively. Small interfering RNA was used to knock down cadherin-11 expression in PDLCs. The collagen matrix of PDLCs was examined using toluidine blue staining. Cadherin-11 was expressed in PDLCs. Mechanical stress suppressed cadherin-11 expression in PDLCs with prolonged force treatment time and increased force intensity, accompanied by suppressed β-catenin expression. Simultaneously, mechanical stress altered cell morphology and repressed Col-I expression in a time- and dose-dependent manner in PDLCs. Moreover, knockdown of cadherin-11 with suppressed β-catenin expression resulted in altered PDLC morphology and repressed collagen expression, which were consistent with the changes observed under mechanical stress. Results of this study suggest that cadherin-11 is expressed in PDLCs and modulates PDLC morphology and collagen synthesis in response to mechanical stress, which may play an important role in the homeostasis and remodeling of the PDL under mechanical stimulation.

  17. Collagen-chitosan scaffold modified with Au and Ag nanoparticles: Synthesis and structure

    Science.gov (United States)

    Rubina, M. S.; Kamitov, E. E.; Zubavichus, Ya. V.; Peters, G. S.; Naumkin, A. V.; Suzer, S.; Vasil'kov, A. Yu.

    2016-03-01

    Nowadays, the dermal biomimetic scaffolds are widely used in regenerative medicine. Collagen-chitosan scaffold one of these materials possesses antibacterial activity, good compatibility with living tissues and has been already used as a wound-healing material. In this article, collagen-chitosan scaffolds modified with Ag and Au nanoparticles have been synthesized using novel method - the metal-vapor synthesis. The nanocomposite materials are characterized by XPS, TEM, SEM and synchrotron radiation-based X-ray techniques. According to XRD data, the mean size of the nanoparticles (NPs) is 10.5 nm and 20.2 nm in Au-Collagen-Chitosan (Au-CollCh) and Ag-Collagen-Chitosan (Ag-CollCh) scaffolds, respectively in fair agreement with the TEM data. SAXS analysis of the composites reveals an asymmetric size distribution peaked at 10 nm for Au-CollCh and 25 nm for Ag-CollCh indicative of particle's aggregation. According to SEM data, the metal-carrying scaffolds have layered structure and the nanoparticles are rather uniformly distributed on the surface material. XPS data indicate that the metallic nanoparticles are in their unoxidized/neutral states and dominantly stabilized within the chitosan-rich domains.

  18. Collagen Homeostasis and Metabolism

    DEFF Research Database (Denmark)

    Magnusson, S Peter; Heinemeier, Katja M; Kjaer, Michael

    2016-01-01

    The musculoskeletal system and its collagen rich tissue is important for ensuring architecture of skeletal muscle, energy storage in tendon and ligaments, joint surface protection, and for ensuring the transfer of muscular forces into resulting limb movement. Structure of tendon is stable and the...

  19. Polysulfated glycosaminoglycan accelerates net synthesis of collagen and glycosaminoglycans by arthritic equine cartilage tissues and chondrocytes.

    Science.gov (United States)

    Glade, M J

    1990-05-01

    Low molecular weight polysulfated glycosaminoglycan (PSGAG) stimulated net collagen and glycosaminoglycan synthesis by normal and arthritic equine fetlock cartilage tissues in organ culture. Arthritic tissues were more sensitive to PSGAG stimulation. The rates of cartilage-specific type-II collagen and chondroitin sulfate-rich glycosaminoglycan synthesis by confluent chondrocyte cell cultures obtained from normal and arthritic equine cartilage tissues were increased by 25 and 50 mg of PSGAG/ml. Cells from arthritic cartilage were also more sensitive to the presence of PSGAG. In addition, concentrations of PSGAG (25 and 50 mg/ml) approximate to those in synovial fluid after intra-articular injection of 250 mg of PSGAG inhibited the rate of collagen and glycosaminoglycan degradation in cell culture. These findings suggest that PSGAG may have a role in the healing of mild cartilage degeneration by encouraging the production of replacement hyaline matrix materials, while delaying their subsequent degradation. In contrast, growth of cell cultures was inhibited by PSGAG, suggesting that these compounds may fail to stimulate chondrocyte replication, a prerequisite for tissue regeneration. Nonetheless, these observations provide direct evidence of a truly chondroprotective role for low molecular weight PSGAG in the treatment of equine degenerative joint disease.

  20. Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short-Term Cyclic Stretching

    Directory of Open Access Journals (Sweden)

    Janina Burk

    2016-01-01

    Full Text Available Tendon and ligament pathologies are still a therapeutic challenge, due to the difficulty in restoring the complex extracellular matrix architecture and biomechanical strength. While progress is being made in cell-based therapies and tissue engineering approaches, comprehensive understanding of the fate of progenitor cells in tendon healing is still lacking. The aim of this study was to investigate the effect of decellularized tendon matrix and moderate cyclic stretching as natural stimuli which could potentially direct tenogenic fate. Equine adipose-derived mesenchymal stromal cells (MSC were seeded on decellularized tendon matrix scaffolds. Mechanical stimulation was applied in a custom-made cyclic strain bioreactor. Assessment was performed 4 h, 8 h, and 24 h following mechanical stimulation. Scaffold culture induced cell alignment and changes in expression of tendon-related genes, although cell viability was decreased compared to monolayer culture. Short mechanical stimulation periods enhanced most of the scaffold-induced effects. Collagen 1A2 expression levels were decreased, while collagen 3A1 and decorin levels were increased. Tenascin-C and scleraxis expression showed an initial decrease but had increased 24 h after stimulation. The results obtained suggest that decellularized tendon matrix, supported by cyclic stretching, can induce tenogenic differentiation and the synthesis of tendon components important for matrix remodeling.

  1. Use of cis-[18F] fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Kjaer, Andreas; Heinemeier, Katja Maria

    2011-01-01

    Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18)F]fluoro-proline (cis-Fpro), for non-invasive assess......Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18)F]fluoro-proline (cis-Fpro), for non......-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days) treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60...

  2. Functionally Distinct Tendons From Elastin Haploinsufficient Mice Exhibit Mild Stiffening and Tendon-Specific Structural Alteration.

    Science.gov (United States)

    Eekhoff, Jeremy D; Fang, Fei; Kahan, Lindsey G; Espinosa, Gabriela; Cocciolone, Austin J; Wagenseil, Jessica E; Mecham, Robert P; Lake, Spencer P

    2017-11-01

    Elastic fibers are present in low quantities in tendon, where they are located both within fascicles near tenocytes and more broadly in the interfascicular matrix (IFM). While elastic fibers have long been known to be significant in the mechanics of elastin-rich tissue (i.e., vasculature, skin, lungs), recent studies have suggested a mechanical role for elastic fibers in tendons that is dependent on specific tendon function. However, the exact contribution of elastin to properties of different types of tendons (e.g., positional, energy-storing) remains unknown. Therefore, this study purposed to evaluate the role of elastin in the mechanical properties and collagen alignment of functionally distinct supraspinatus tendons (SSTs) and Achilles tendons (ATs) from elastin haploinsufficient (HET) and wild type (WT) mice. Despite the significant decrease in elastin in HET tendons, a slight increase in linear stiffness of both tendons was the only significant mechanical effect of elastin haploinsufficiency. Additionally, there were significant changes in collagen nanostructure and subtle alteration to collagen alignment in the AT but not the SST. Hence, elastin may play only a minor role in tendon mechanical properties. Alternatively, larger changes to tendon mechanics may have been mitigated by developmental compensation of HET tendons and/or the role of elastic fibers may be less prominent in smaller mouse tendons compared to the larger bovine and human tendons evaluated in previous studies. Further research will be necessary to fully elucidate the influence of various elastic fiber components on structure-function relationships in functionally distinct tendons.

  3. Fabrication of nanocomposites by collagen templated synthesis of layered double hydroxides assisted by an acrylic silane coupling agent

    Science.gov (United States)

    Sun, Yanqing; Zhou, Yuming; Wang, Zhiqiang; Ye, Xiaoyun

    2009-02-01

    The purpose of this study was to control the fabrication of nanocomposites at the nanoscale interface by collagen templated synthesis of Zn-Al layered double hydroxides (LDHs) assisted by γ-methacryloxypropyl trimethoxy silane (KH570) with further treatment of graft polymerization. The results show that collagen directs the growth of LDHs into curved nanorods by length of 300 nm in perfect consistency with collagen chain in both the size and flexility under the essential hydrophobic environment on the solid surface provided by KH570. The nanorods are aggregated into thin curved platelets due to strong interaction between collagen molecules themselves and strong interaction between collagen and LDH sheets. By further treatment of graft polymerization, the adjacent curved platelets encircle into numerous hollows via chemical linkage, achieving polyporous nanocomposites. Nanohybrid materials with this structure are especially interesting for applications as biosensors or supported catalysis.

  4. Design and synthesis of collagen mimetic peptide derivatives for studying triple helix assembly and collagen mimetic peptide-collagen binding interaction

    Science.gov (United States)

    Mo, Xiao

    2008-10-01

    Collagen is the principal tensile clement of the extra-cellular matrix in mammals and is the basic scaffold for cells and tissues. Collagen molecules are comprised of homo-trimeric helices (e.g. collagen type II and type III), ABB type hetero-trimeric helices (e.g. collagen type I, type IV, and type V), or ABC type hetero-trimeric helices (e.g. type V). Mimicry of collagen structures can help elucidate collagen triple helical conformation and provide insights into making novel collagen-like biomaterials. Our group previously reported a new physical collagen modification method, which was based on non-covalent interaction between collagen mimetic peptide (CMP: -(Pro-Hyp-Gly) x-) and natural collagen. We hypothesized that CMP binds to collagen through a process involving both strand invasion and triple helix assembly. The aim of this dissertation is to study structural formation and stability of collagen triple helix, and to investigate CMP-collagen binding interactions using two types of CMP derivatives: covalently templated CMP trimer and CMP-nanoparticle conjugates. We demonstrated that covalently templated ABB type CMP hetero-trimers could be prepared by a versatile synthetic strategy involving both solid phase and solution peptide coupling. Our thermal melting studies showed that the templated CMP hetero-trimers formed collagen-like triple helices and their folding kinetics correlated with the amino acid compositions of the individual CMP strands. We also studied the thermal melting behavior and folding kinetics of a templated hetero-trimer complex comprised of CMP and a peptide derived from collagen. This synthetic strategy can be readily extended to synthesize other ABB type hetero-trimers to investigate their local melting behavior and biological activity. We also prepared colloidally stable CMP functionalized gold nanoparticles (Au-CMPs) as a TEM marker for investigating the CMP-collagen interaction. Au-CMP showed preferential binding to collagen fiber's gap

  5. Corneal collagens.

    Science.gov (United States)

    Robert, L; Legeais, J M; Robert, A M; Renard, G

    2001-05-01

    Cornea is a highly differentiated tissue rich in extracellular matrix (ECM) specifically distributed in space in order to insure its dual role--transparency and protection of inner eye-tissues. Corneal ECM is especially rich in collagens. Since the characterisation of a number of distinct collagen types it appeared that most of them are present in the cornea. Their synthesis follows a specific program of sequential expression of the different collagen types to be synthesised during the development and maturation of the cornea. The precise regulation of the diameter and orientation of fibers, and of the interfibrillar spaces is partially at least attributed to interactions between glycosaminoglycans and collagens. The 'program' of vectorial collagen synthesis and GAG-collagen interactions changes also with age and in several pathological conditions as corneal dystrophies and wound healing. The Maillard reaction, especially in diabetes, is one of these important factors involved in age-dependent modifications of corneal structure and function. Far from being inert, corneal collagens were shown to have relatively short half-lives. The biosynthesis of corneal collagens was studied also during wound healing. The refibrillation of wounded corneas does not follow the original 'program' of ECM-synthesis as shown by the comparative study of wound healing using biochemical and morphometric methods. This review recapitulates briefly previous and recent studies on corneal collagens in order to present to clinicians and scientists an overview of the state of the art of this important field at the intersection of eye research and matrix biology.

  6. Achilles Tendonitis

    Science.gov (United States)

    ... You Treat Achilles Tendonitis? en español Tendinitis de Aquiles Kim didn't do much over the summer ... Achilles Tendonitis and Who Gets It? Your Achilles tendon is located at the back of your foot, ...

  7. Two-dimensional collagen-graphene as colloidal templates for biocompatible inorganic nanomaterial synthesis.

    Science.gov (United States)

    Kumari, Divya; Sheikh, Lubna; Bhattacharya, Soumya; Webster, Thomas J; Nayar, Suprabha

    2017-01-01

    In this study, natural graphite was first converted to collagen-graphene composites and then used as templates for the synthesis of nanoparticles of silver, iron oxide, and hydroxyapatite. X-ray diffraction did not show any diffraction peaks of graphene in the composites after inorganic nucleation, compared to the naked composite which showed (002) and (004) peaks. Scanning electron micrographs showed lateral gluing/docking of these composites, possibly driven by an electrostatic attraction between the positive layers of one stack and negative layers of another, which became distorted after inorganic nucleation. Docking resulted in single layer-like characteristics in certain places, as seen under transmission electron microscopy, but sp 2 /sp 3 ratios from Raman analysis inferred three-layer composite formation. Strain-induced folding of these layers into uniform clusters at the point of critical nucleation, revealed beautiful microstructures under scanning electron microscopy. Lastly, cell viability studies using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed the highest cell viability for the collagen-graphene-hydroxyapatite composites. In this manner, this study provided - to the field of nanomedicine - a new process for the synthesis of several nanoparticles (with low toxicity) of high interest for numerous medical applications.

  8. STAT6-Dependent Collagen Synthesis in Human Fibroblasts Is Induced by Bovine Milk.

    Directory of Open Access Journals (Sweden)

    Stefan Kippenberger

    Full Text Available Since the domestication of the urus, 10.000 years ago, mankind utilizes bovine milk for different purposes. Besides usage as a nutrient also the external application of milk on skin has a long tradition going back to at least the ancient Aegypt with Cleopatra VII as a great exponent. In order to test whether milk has impact on skin physiology, cultures of human skin fibroblasts were exposed to commercial bovine milk. Our data show significant induction of proliferation by milk (max. 2,3-fold, EC50: 2,5% milk without toxic effects. Surprisingly, bovine milk was identified as strong inducer of collagen 1A1 synthesis at both, the protein (4-fold, EC50: 0,09% milk and promoter level. Regarding the underlying molecular pathways, we show functional activation of STAT6 in a p44/42 and p38-dependent manner. More upstream, we identified IGF-1 and insulin as key factors responsible for milk-induced collagen synthesis. These findings show that bovine milk contains bioactive molecules that act on human skin cells. Therefore, it is tempting to test the herein introduced concept in treatment of atrophic skin conditions induced e.g. by UV light or corticosteroids.

  9. STAT6-Dependent Collagen Synthesis in Human Fibroblasts Is Induced by Bovine Milk.

    Science.gov (United States)

    Kippenberger, Stefan; Zöller, Nadja; Kleemann, Johannes; Müller, Jutta; Kaufmann, Roland; Hofmann, Matthias; Bernd, August; Meissner, Markus; Valesky, Eva

    2015-01-01

    Since the domestication of the urus, 10.000 years ago, mankind utilizes bovine milk for different purposes. Besides usage as a nutrient also the external application of milk on skin has a long tradition going back to at least the ancient Aegypt with Cleopatra VII as a great exponent. In order to test whether milk has impact on skin physiology, cultures of human skin fibroblasts were exposed to commercial bovine milk. Our data show significant induction of proliferation by milk (max. 2,3-fold, EC50: 2,5% milk) without toxic effects. Surprisingly, bovine milk was identified as strong inducer of collagen 1A1 synthesis at both, the protein (4-fold, EC50: 0,09% milk) and promoter level. Regarding the underlying molecular pathways, we show functional activation of STAT6 in a p44/42 and p38-dependent manner. More upstream, we identified IGF-1 and insulin as key factors responsible for milk-induced collagen synthesis. These findings show that bovine milk contains bioactive molecules that act on human skin cells. Therefore, it is tempting to test the herein introduced concept in treatment of atrophic skin conditions induced e.g. by UV light or corticosteroids.

  10. Development of biomimetic tilapia collagen nanofibers for skin regeneration through inducing keratinocytes differentiation and collagen synthesis of dermal fibroblasts.

    Science.gov (United States)

    Zhou, Tian; Wang, Nanping; Xue, Yang; Ding, Tingting; Liu, Xin; Mo, Xiumei; Sun, Jiao

    2015-02-11

    In this study, tilapia skin collagen sponge and electrospun nanofibers were developed for wound dressing. The collagen sponge was composed of at least two α-peptides, and its denaturation temperature was 44.99 °C. It did not change the number of spleen-derived lymphocytes in BALB/c mice, the ratio of CD4+/CD8+ lymphocytes, and the level of IgG or IgM in Sprague-Dawley rat. The contact angle, tensile strength, and weight loss temperature of collagen nanofibers were 21.2°, 6.72±0.44 MPa, and 300 °C, respectively. The nanofibers could promote the viabilities of human keratinocytes (HaCaTs) and human dermal fibroblasts (HDFs), inducing epidermal differentiation through the gene expression of involucrin, filaggrin, and type I transglutaminase of HaCaTs, and they could also accelerate migration of HaCaTs with the expression of matrix metalloproteinase-9 and transforming growth factor-β1 (TGF-β1). Besides, the nanofibers could upregulate the protien level of Col-I in HDFs both via a direct effect and TGF-β1 secreted from HaCaTs, thus facilitating the formation of collagen fibers. Furthermore, the collagen nanofibers stimulated the skin regeneration rapidly and effectively in vivo. These biological effects could be explained as the contributions from the biomimic extracellular cell matrix structure, hydrophilicity, and the multiple amino acids of the collagen nanofibers.

  11. How Obesity Affects Tendons?

    Science.gov (United States)

    Abate, Michele; Salini, Vincenzo; Andia, Isabel

    Several epidemiological and clinical observations have definitely demonstrated that obesity has harmful effects on tendons. The pathogenesis of tendon damage is multi-factorial. In addition to overload, attributable to the increased body weight, which significantly affects load-bearing tendons, systemic factors play a relevant role. Several bioactive peptides (chemerin, leptin, adiponectin and others) are released by adipocytes, and influence tendon structure by means of negative activities on mesenchymal cells. The ensuing systemic state of chronic, sub-clinic, low-grade inflammation can damage tendon structure. Metabolic disorders (diabetes, impaired glucose tolerance, and dislipidemia), frequently associated with visceral adiposity, are concurrent pathogenetic factors. Indeed, high glucose levels increase the formation of Advanced Glycation End-products, which in turn form stable covalent cross-links within collagen fibers, modifying their structure and functionality.Sport activities, so useful for preventing important cardiovascular complications, may be detrimental for tendons if they are submitted to intense acute or chronic overload. Therefore, two caution rules are mandatory: first, to engage in personalized soft training program, and secondly to follow regular check-up for tendon pathology.

  12. Human Achilles tendon glycation and function in diabetes

    DEFF Research Database (Denmark)

    Couppé, Christian; Svensson, Rene Brüggebusch; Madsen, Mads Kongsgaard

    2016-01-01

    Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between...... collagen glycation, Achilles tendon stiffness parameters and plantar pressure in poorly (n = 22) and well (n = 22) controlled diabetic patients, including healthy age matched (45-70 yrs) controls (n = 11). There were no differences in any of outcome parameters (collagen cross-linking or tendon stiffness...... concentrations (55%, P Achilles tendon material stiffness was higher in DB (54%, P Achilles tendon material stiffness and skin connective...

  13. Histopathological findings in chronic tendon disorders.

    Science.gov (United States)

    Järvinen, M; Józsa, L; Kannus, P; Järvinen, T L; Kvist, M; Leadbetter, W

    1997-04-01

    Tendon injuries and other tendon disorders represent a common diagnostic and therapeutic challenge in sports medicine, resulting in chronic and long-lasting problems. Tissue degeneration is a common finding in many sports-related tendon complaints. In the great majority of spontaneous tendon ruptures, chronic degenerative changes are seen at the rupture site of the tendon (1). Systemic diseases and diseases specifically deteriorating the normal structure of the tendon (i.e. foreign bodies, and metabolic, inherited and infectious tendon diseases) are only rarely the cause of tendon pathology. Inherited diseases, such as various hereditary diseases with disturbed collagen metabolism and characteristic pathological structural alterations (Ehlers-Danlos syndrome, Marfani syndrome, homocystinuria (ochronosis)), represent approximately 1% of the causes of chronic tendon complaints (2), whereas foreign bodies are somewhat more common and are found in less than 10% of all chronic tendon problems (1). Rheumatoid arthritis and sarcoidosis are typical systemic diseases that cause chronic inflammation in tendon and peritendinous tissues. Altogether, these 'specific' disorders represented less than 2% of the pathological alterations found in the histological analysis of more than 1000 spontaneously ruptured tendons (1, 3, 4). In this material, degenerative changes were seen in a great majority of the tendons, indicating that a spontaneous tendon rupture is a typical clinical end-state manifestation of a degenerative process in the tendon tissue. The role of overuse in the pathogenesis of chronic tendon injuries and disorders is not completely understood. It has been speculated that when tendon is overused it becomes fatigued and loses its basal reparative ability, the repetitive microtraumatic processes thus overwhelming the ability of the tendon cells to repair the fiber damage. The intensive repetitive activity, which often is eccentric by nature, may lead to cumulative

  14. Delayed exercise promotes remodeling in sub-rupture fatigue damaged tendons.

    Science.gov (United States)

    Bell, R; Boniello, M R; Gendron, N R; Flatow, E L; Andarawis-Puri, N

    2015-06-01

    Tendinopathy is a common musculoskeletal injury whose treatment is limited by ineffective therapeutic interventions. Previously we have shown that tendons ineffectively repair early sub-rupture fatigue damage. In contrast, physiological exercise has been shown to promote remodeling of healthy tendons but its utility as a therapeutic to promote repair of fatigue damaged tendons remains unknown. Therefore, the objective of this study was to assess the utility of exercise initiated 1 and 14 days after onset of fatigue damage to promote structural repair in fatigue damaged tendons. We hypothesized that exercise initiated 14 days after fatigue loading would promote remodeling as indicated by a decrease in area of collagen matrix damage, increased procollagen I and decorin, while decreasing proteins indicative of tendinopathy. Rats engaged in 6-week exercise for 30 min/day or 60 min/day starting 1 or 14 days after fatigue loading. Initiating exercise 1-day after onset of fatigue injury led to exacerbation of matrix damage, particularly at the tendon insertion. Initiating exercise 14 days after onset of fatigue injury led to remodeling of damaged regions in the midsubstance and collagen synthesis at the insertion. Physiological exercise applied after the initial biological response to injury has dampened can potentially promote remodeling of damaged tendons. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. Effects of the Nd:YAG laser on DNA synthesis and collagen production in human skin fibroblast cultures

    Energy Technology Data Exchange (ETDEWEB)

    Castro, D.J.; Abergel, R.P.; Meeker, C.; Dwyer, R.M.; Lesavoy, M.A.; Uitto, J.

    1983-09-01

    Human skin fibroblasts were subjected to treatment with a Neodymium:YAG laser at 1060 nm with varying levels of energy determined by a reproducible method of dosimetry. DNA synthesis in the cells was measured by the incorporation of (3H)thymidine, and collagen production was monitored by the synthesis of nondialyzable (3H)hydroxyproline after incubation of cells with (3H)proline. Using energy levels equal to 1.7 X 10(3) J/cm2, a significant reduction in DNA synthesis was noted, while the cells remained viable as tested by the trypan blue exclusion test. With energy levels higher or equal to 2.3 X 10(3) J/cm2, the suppression of DNA synthesis was accompanied by cell nonviability. The collagen production, when measured immediately following the treatment with 1.7 X 10(3) J/cm2, was markedly reduced, and similar effects were observed with higher energy levels. However, when the cells were tested for collagen production at 20 hours following laser treatment, there was a significant decrease in collagen production at energy levels as low as 1.1 X 10(3) J/cm2, a dose that did not affect DNA synthesis or cell viability. Thus, the results indicate that the Nd:YAG laser can selectively suppress collagen production without affecting cell proliferation. These observations suggest that laser treatment could potentially be used to reduce collagen deposition in conditions such as keloids and hypertrophic scars.

  16. Bioinspired synthesis of hydroxyapatite nanocrystals in the presence of collagen and l-arginine: Candidates for bone regeneration.

    Science.gov (United States)

    Brasinika, Despoina; Tsigkou, Olga; Tsetsekou, Athena; Missirlis, Yiannis F

    2016-04-01

    This work aims at the bioinspired synthesis of hydroxyapatite (HAp) crystals in the presence of both collagen and l-arginine, in an effort to obtain a homogeneous hybrid material, having a bone-like nanostructure. Collagen (Col) is the most commonly utilized protein in most species of life, while L-arginine (Arg) encourages cell attachment, proliferation, and differentiation on HAp surfaces. Transmission electron microscopy, X-ray diffraction and Fourier transform-infrared spectroscopy were used to analyze surface morphology and structure of nanocrystals obtained under different synthesis conditions. It was shown that collagen and arginine content affect HAp crystallization. Collagen has an inhibition effect since HAp crystal size is reduced with the increase of collagen content. The presence of arginine is crucial as a critical content exists (Ca(2+):Arg = 1:1) under which HAp nanocrystals coexist with brushite. Under the optimum synthesis conditions (HAp/Col weight ratio 70/30 and Ca(2+):Arg molar ratio 1:1) HAp nanoplates of a uniform size (around 10 × 10 nm) were obtained. The biocompatibility of this hybrid powder was assessed using human bone marrow derived mesenchymal stem cells (MSCs). Cell response in terms of MSC attachment (scanning electron microscopy) and viability/proliferation (Alamar Blue) demonstrated a noncytotoxic effect of the new material. © 2015 Wiley Periodicals, Inc.

  17. Biochemical markers of type II collagen breakdown and synthesis are positioned at specific sites in human osteoarthritic knee cartilage

    DEFF Research Database (Denmark)

    Jensen, Anne-Christine Bay; Levin Andersen, Thomas; Charni-Ben Tabassi, N

    2007-01-01

    sections were obtained from full-depth cartilage biopsies from 32 OA knees. Immunohistochemistry was performed for Helix-II and CTX-II, which are type II collagen fragments originating from the triple helix and the telopeptide region, respectively, and believed to reflect distinct breakdown events, as well......OBJECTIVE: To investigate whether type II collagen turnover markers used for osteoarthritis (OA) activity evaluation in body fluids can be detected at the level of specific histological features of OA cartilage tissue, as well as how they relate with each other at this level. METHODS: Adjacent...... as for type IIA N propeptide (PIIANP), a biochemical marker reflecting synthesis of type IIA collagen. RESULTS: Helix-II and CTX-II were detected in areas where collagen damage was reported previously, most frequently around chondrocytes, but also frequently in regions not previously investigated...

  18. Structural and Ultrastructural Characteristics of Bone-Tendon Junction of the Calcaneal Tendon of Adult and Elderly Wistar Rats.

    Directory of Open Access Journals (Sweden)

    Diego Pulzatto Cury

    Full Text Available Tendons are transition tissues that transfer the contractile forces generated by the muscles to the bones, allowing movement. The region where the tendon attaches to the bone is called bone-tendon junction or enthesis and may be classified as fibrous or fibrocartilaginous. This study aims to analyze the collagen fibers and the cells present in the bone-tendon junction using light microscopy and ultrastructural techniques as scanning electron microscopy and transmission electron microscopy. Forty male Wistar rats were used in the experiment, being 20 adult rats at 4 months-old and 20 elderly rats at 20 months-old. The hind limbs of the rats were removed, dissected and prepared to light microscopy, transmission electron microscopy and scanning electron microscopy. The aging process showed changes in the collagen fibrils, with a predominance of type III fibers in the elderly group, in addition to a decrease in the amount of the fibrocartilage cells, fewer and shorter cytoplasmic processes and a decreased synthetic capacity due to degradation of the organelles involved in synthesis.

  19. Collagen-based silver nanoparticles for biological applications: synthesis and characterization.

    Science.gov (United States)

    Cardoso, Vinicius S; Quelemes, Patrick V; Amorin, Adriany; Primo, Fernando Lucas; Gobo, Graciely Gomides; Tedesco, Antonio C; Mafud, Ana C; Mascarenhas, Yvonne P; Corrêa, José Raimundo; Kuckelhaus, Selma A S; Eiras, Carla; Leite, José Roberto S A; Silva, Durcilene; dos Santos Júnior, José Ribeiro

    2014-09-17

    Type I collagen is an abundant natural polymer with several applications in medicine as matrix to regenerate tissues. Silver nanoparticles is an important nanotechnology material with many utilities in some areas such as medicine, biology and chemistry. The present study focused on the synthesis of silver nanoparticles (AgNPs) stabilized with type I collagen (AgNPcol) to build a nanomaterial with biological utility. Three formulations of AgNPcol were physicochemical characterized, antibacterial activity in vitro and cell viability assays were analyzed. AgNPcol was characterized by means of the following: ultraviolet-visible spectroscopy, dynamic light scattering analysis, Fourier transform infrared spectroscopy, atomic absorption analysis, transmission electron microscopy and of X-ray diffraction analysis. All AgNPcol showed spherical and positive zeta potential. The AgNPcol at a molar ratio of 1:6 showed better characteristics, smaller hydrodynamic diameter (64.34 ± 16.05) and polydispersity index (0.40 ± 0.05), and higher absorbance and silver reduction efficiency (0.645 mM), when compared with the particles prepared in other mixing ratios. Furthermore, these particles showed antimicrobial activity against both Staphylococcus aureus and Escherichia coli and no toxicity to the cells at the examined concentrations. The resulted particles exhibited favorable characteristics, including the spherical shape, diameter between 64.34 nm and 81.76 nm, positive zeta potential, antibacterial activity, and non-toxicity to the tested cells (OSCC).

  20. Effect of testosterone on the proliferation and collagen synthesis of cardiac fibroblasts induced by angiotensin II in neonatal rat.

    Science.gov (United States)

    Yang, Xiaocun; Wang, Ying; Yan, Shuxun; Sun, Lina; Yang, Guojie; Li, Yuan; Yu, Chaonan

    2017-01-02

    The objective is to explore the effect of testosterone on the proliferation and collagen synthesis of neonatal rat cardiac fibroblasts (CF) induced by Angiotensin II (Ang II) and the underlying mechanisms. Derived from neonatal rats, the CFs were divided into 4 groups: the control group, Ang II group, testosterone group, and testosterone + Ang II group in vitro. Cell cycle distribution, collagen counts, and phosphorylated extracellular signal-regulated kinase (ERK1/2) (p - ERK1/2) expression were assessed by flow cytometry, VG staining, and immunocytochemistry, respectively. The Ang II group had a much higher proportion of cells in the S-phase, higher collagen contents, and a higher p - ERK1/2 expression level than either the control or testosterone group. However, these factors were significantly reduced in the testosterone + Ang II group as compared to the Ang II group. In terms of cells in the S-phase and the collagen contents, there was not a significant difference between the testosterone group and the control. However, the protein expression of p-ERK1/2 was significantly increased in the testosterone group as compared to the control. Testosterone inhibits the proliferation and collagen synthesis of CF induced by Ang II. The underlying mechanism may involve the ERK1/2 signaling pathway.

  1. Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System

    Directory of Open Access Journals (Sweden)

    Shan-Shan Liu

    2013-12-01

    Full Text Available The exact molecular mechanism that mediates hypoxia-induced pulmonary fibrosis needs to be further clarified. The aim of this study was to explore the effect and underlying mechanism of angiotensin II (Ang II on collagen synthesis in hypoxic human lung fibroblast (HLF cells. The HLF-1 cell line was used for in vitro studies. Angiotensinogen (AGT, angiotensin converting enzyme (ACE, angiotensin II type 1 receptor (AT1R and angiotensin II type 2 receptor (AT2R expression levels in human lung fibroblasts were analysed using real-time polymerase chain reaction (RT-PCR after hypoxic treatment. Additionally, the collagen type I (Col-I, AT1R and nuclear factor κappaB (NF-κB protein expression levels were detected using Western blot analysis, and NF-κB nuclear translocation was measured using immunofluorescence localization analysis. Ang II levels in HLF-1 cells were measured with an enzyme-linked immunosorbent assay (ELISA. We found that hypoxia increased Col-I mRNA and protein expression in HLF-1 cells, and this effect could be inhibited by an AT1R or AT2R inhibitor. The levels of NF-κB, RAS components and Ang II production in HLF-1 cells were significantly increased after the hypoxia exposure. Hypoxia or Ang II increased NF-κB-p50 protein expression in HLF-1 cells, and the special effect could be inhibited by telmisartan (TST, an AT1R inhibitor, and partially inhibited by PD123319, an AT2R inhibitor. Importantly, hypoxia-induced NF-κB nuclear translocation could be nearly completely inhibited by an AT1R or AT2R inhibitor. Furthermore pyrrolidine dithiocarbamate (PDTC, a NF-κB blocker, abolished the expression of hypoxia-induced AT1R and Col-I in HLF-1 cells. Our results indicate that Ang II-mediated NF-κB signalling via ATR is involved in hypoxia-induced collagen synthesis in human lung fibroblasts.

  2. Promotion of minTBP-1-PRGDN on the attachment, proliferation and collagen I synthesis of human keratocyte on titanium

    Directory of Open Access Journals (Sweden)

    Xin-Yu Li

    2014-02-01

    Full Text Available AIM:To investigate the influence of minTBP-1-PRGDN on the attachment, proliferation and collagen I synthesis of human keratocyte on titanium (Ti surface.METHODS:The chimeric peptide RKLPDAPRGDN (minTBP-1-PRGDN was synthesized by connecting RKLPDA (minTBP-1 to the N-terminal of PRGDN , the influence of minTBP-1-PRGDN on the attachment, proliferation and collagen I synthesis of human keratocyte on Ti surface were tested using PRGDN and minTBP-1as controls. The keratocytes attached to the surface of Ti were either stained with FITC-labeled phalloidin and viewed with fluorescence microscope or quantified with alamar Blue method. The proliferation of keratocytes on Ti were quantified with 3-(4,5-dim- ethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide up-taking methods. The secretion of type I collagen were determined using an ELISA kit.RESULTS:The results showed that minTBP-1-PRGDN at a concentration of 100ng/mL was the most potent peptide to enhance the attachment of human keratocytes to the surface of Ti (1.40±0.03 folds, P=0.003, to promote the proliferation (1.26±0.05 folds, P=0.014 and the synthesis of type I collagen (1.530±0.128, P=0.008. MinTBP-1 at the same concentration could only promote the attachment (1.13±0.04 folds, P=0.020 and proliferation(1.15±0.06 folds, P=0.021, while PRGDN had no significant influence (P>0.05.CONCLUSION:Our data shows that the novel chimeric peptide minTBP-1-PRGDN could promote the attachment, proliferation and type I collagen synthesis of human keratocytes on the surface of Ti.

  3. Promotion of minTBP-1-PRGDN on the attachment, proliferation and collagen I synthesis of human keratocyte on titanium.

    Science.gov (United States)

    Li, Xin-Yu; Ji, Cai-Ni; Xu, Ling-Juan; Hu, Wei-Kun; Zhou, Bin; Li, Gui-Gang

    2014-01-01

    To investigate the influence of minTBP-1-PRGDN on the attachment, proliferation and collagen I synthesis of human keratocyte on titanium (Ti) surface. The chimeric peptide RKLPDAPRGDN (minTBP-1-PRGDN) was synthesized by connecting RKLPDA (minTBP-1) to the N-terminal of PRGDN, the influence of minTBP-1-PRGDN on the attachment, proliferation and collagen I synthesis of human keratocyte on Ti surface were tested using PRGDN and minTBP-1as controls. The keratocytes attached to the surface of Ti were either stained with FITC-labeled phalloidin and viewed with fluorescence microscope or quantified with alamar Blue method. The proliferation of keratocytes on Ti were quantified with 3-(4,5-dim- ethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide up-taking methods. The secretion of type I collagen were determined using an ELISA kit. The results showed that minTBP-1-PRGDN at a concentration of 100ng/mL was the most potent peptide to enhance the attachment of human keratocytes to the surface of Ti (1.40±0.03 folds, P=0.003), to promote the proliferation (1.26±0.05 folds, P=0.014) and the synthesis of type I collagen (1.530±0.128, P=0.008). MinTBP-1 at the same concentration could only promote the attachment (1.13±0.04 folds, P=0.020) and proliferation(1.15±0.06 folds, P=0.021), while PRGDN had no significant influence (P>0.05). Our data shows that the novel chimeric peptide minTBP-1-PRGDN could promote the attachment, proliferation and type I collagen synthesis of human keratocytes on the surface of Ti.

  4. Tendon Force Transmission at the Nanoscale

    DEFF Research Database (Denmark)

    Svensson, René

    2013-01-01

    of connective tissue function that are poorly understood. One such aspect is the microscopic mechanisms of force transmission through tendons over macroscopic distances. Force transmission is at the heart of tendon function, but the large range of scales in the hierarchical structure of tendons has made...... it difficult to tackle. The tendon hierarchy ranges from molecules (2 nm) over fibrils (200 nm), fibers (2 μm) and fascicles (200 μm) to tendons (10 mm), and to derive the mechanisms of force transmission it is necessary to know the mechanical behavior at each hierarchical level. The aim of the present work...... was to elucidate the mechanisms of force transmission in tendons primarily by investigating the mechanical behavior at the hierarchical level of collagen fibrils. To do so we have developed an atomic force microscopy (AFM) method for tensile testing of native collagen fibrils. The thesis contains five papers...

  5. Fracture mechanics of collagen fibrils

    DEFF Research Database (Denmark)

    Svensson, Rene B; Mulder, Hindrik; Kovanen, Vuokko

    2013-01-01

    Tendons are important load-bearing structures, which are frequently injured in both sports and work. Type I collagen fibrils are the primary components of tendons and carry most of the mechanical loads experienced by the tissue, however, knowledge of how load is transmitted between and within fib...

  6. Pyropia yezoensis peptide promotes collagen synthesis by activating the TGF-?/Smad signaling pathway in the human dermal fibroblast cell line Hs27

    OpenAIRE

    Kim, Cho-Rong; Kim, Young-Min; Lee, Min-Kyeong; Kim, In-Hye; CHOI, YOUN-HEE; NAM, TAEK-JEONG

    2016-01-01

    Pyropia yezoensis (P. yezoensis) is a marine algae that exhibits antioxidant, anti-inflammatory, antitumor and anti-aging activities. In this study, we investigated the effects of the P. yezoensis peptide, PYP1-5, on collagen synthesis in the human dermal fibroblast cell line Hs27. Skin aging is related to reduced collagen production and the activities of multiple enzymes, including matrix metalloproteinases (MMPs), which degrade collagen structure in the dermis, and tissue inhibitor of tissu...

  7. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

    Science.gov (United States)

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  8. Synthesis of collagen by bovine chondrocytes cultured in alginate; posttranslational modifications and cell-matrix interaction

    NARCIS (Netherlands)

    Beekman, B.; Verzijl, N.; Bank, R.A.; Von Der Mark, K.; TeKoppele, J.M.

    1997-01-01

    The extracellular matrix synthesized by articular chondrocytes cultured in alginate beads was investigated. Collagen levels increased sigmoidally with time and remained constant after 2 weeks of culture. The presence of cartilage-specific type II collagen was confirmed immunohistochemically.

  9. Tendon Injuries

    Science.gov (United States)

    ... What OT Can Do: Video For Professionals Ethics Tendon Injuries When a person experiences a tendon injury in the hand that affects the ability ... plan. What can a person with a hand tendon injury do? Implement a home exercise program recommended ...

  10. Influence of tetrahydrocurcumin on tail tendon collagen contents and its properties in rats with streptozotocin-nicotinamide-induced type 2 diabetes.

    Science.gov (United States)

    Pari, Leelavinothan; Murugan, Pidaran

    2007-12-01

    Changes in the structural and functional properties of collagen caused by advanced glycation might be of importance for the etiology of late-stage complications in diabetics. Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin, exhibiting many of the same physiological and pharmacological activities of curcumin and in some systems may exert greater antioxidant activity than curcumin. In diabetic rats, hydroxyproline and collagen content as well as its degree of cross-linking were increased, as shown by increased extent of glycation, collagen-linked fluorescence, neutral salt collagen, and decreased acid and pepsin solubility. Administration of THC for 45 days to diabetic rats significantly reduced the accumulation and cross-linking of collagen. The effects of THC were comparable with those of curcumin. In conclusion, administration of THC had a positive influence on the content of collagen and its properties in streptozotocin- and nicotinamide-induced diabetic rats. THC was found to be more effective than curcumin.

  11. Myofibroblasts are responsible for collagen synthesis in the stroma of human hepatocellular carcinoma: an in vivo and in vitro study.

    Science.gov (United States)

    Faouzi, S; Le Bail, B; Neaud, V; Boussarie, L; Saric, J; Bioulac-Sage, P; Balabaud, C; Rosenbaum, J

    1999-02-01

    Marked changes in extracellular matrix occur in the stroma of hepatocellular carcinoma, as compared to normal or cirrhotic liver. The cell types responsible for extracellular matrix synthesis within hepatocellular carcinoma have not been clearly identified. In vivo collagen synthesis was studied by in situ hybridization and immunohistochemistry for types I, IV, V and VI collagen, together with immunolabeling of alpha-smooth muscle actin, a myofibroblast marker, and CD34, an endothelial cell marker. In vitro, extracellular matrix deposition by cultured myofibroblasts was studied by reticulin staining, immunocytochemistry and RNase protection. All collagens studied were expressed in the stroma of the tumor, with a higher level of type VI and IV collagens than of type I and V. The majority of the cells expressing collagen transcripts in human hepatocellular carcinoma stroma were alpha-actin positive and CD 34 negative. In vitro experiments demonstrated that the hepatocellular carcinoma cell lines HepG2, HuH7 and Hep3B markedly increased extracellular matrix deposition by human liver myofibroblasts. This increase was mediated by a soluble mediator present in tumor cell conditioned medium. It was not explained by an increase in mRNA levels of extracellular matrix components, nor by a decrease in the secretion of matrix-degrading proteinases by myofibroblasts. Myofibroblasts are the main source of collagens in the stroma of hepatocellular carcinoma. Our data also indicate that tumoral hepatocytes increase extracellular matrix deposition by cultured myofibroblasts, probably by post-transcriptional mechanisms. The generation of hepatocellular carcinoma stroma by myofibroblasts could thus be under control of tumoral cells.

  12. MicroRNA29a Treatment Improves Early Tendon Injury.

    Science.gov (United States)

    Watts, Ashlee E; Millar, Neal L; Platt, Josh; Kitson, Susan M; Akbar, Moeed; Rech, Raquel; Griffin, Jay; Pool, Roy; Hughes, Tom; McInnes, Iain B; Gilchrist, Derek S

    2017-10-04

    Tendon injuries (tendinopathies) are common in human and equine athletes and characterized by dysregulated collagen matrix, resulting in tendon damage. We have previously demonstrated a functional role for microRNA29a (miR29a) as a post-transcriptional regulator of collagen 3 expression in murine and human tendon injury. Given the translational potential, we designed a randomized, blinded trial to evaluate the potential of a miR29a replacement therapy as a therapeutic option to treat tendinopathy in an equine model that closely mimics human disease. Tendon injury was induced in the superficial digital flexor tendon (SDFT) of 17 horses. Tendon lesions were treated 1 week later with an intralesional injection of miR29a or placebo. miR29a treatment reduced collagen 3 transcript levels at week 2, with no significant changes in collagen 1. The relative lesion cross-sectional area was significantly lower in miR29a tendons compared to control tendons. Histology scores were significantly better for miR29a-treated tendons compared to control tendons. These data support the mechanism of microRNA-mediated modulation of early pathophysiologic events that facilitate tissue remodeling in the tendon after injury and provides a strong proof of principle that a locally delivered miR29a therapy improves early tendon healing. Copyright © 2017 The American Society of Gene and Cell Therapy. All rights reserved.

  13. Region-specific mechanical properties of the human patella tendon

    DEFF Research Database (Denmark)

    Haraldsson, B T; Aagaard, P; Krogsgaard, M

    2004-01-01

    The present study investigated the mechanical properties of tendon fascicles from the anterior and posterior human patellar tendon. Collagen fascicles from the anterior and posterior human patellar tendon in healthy young men (mean +/- SD, 29.0 +/- 4.6 yr, n = 6) were tested in a mechanical rig. ...

  14. Cell viability, collagen synthesis and cytokine expression in human osteoblasts following incubation with generated wear particles using different bone cements.

    Science.gov (United States)

    Schulze, Christoph; Lochner, Katrin; Jonitz, Anika; Lenz, Robert; Duettmann, Oliver; Hansmann, Doris; Bader, Rainer

    2013-07-01

    In total hip arthroplasty, wear particles generated at articulating surfaces and interfaces between bone, cement and implants have a negative impact on osteoblasts, leading to osteolysis and implant loosening. The aim of this experimental study was to determine the effects of particulate wear debris generated at the interface between straight stainless steel hip stems (Exeter(®)) and three different bone cements (Palacos(®) R, Simplex™ P and Cemex(®) Genta) on cell viability, collagen synthesis and cytokine expression in human osteoblasts. Primary osteoblasts were treated with various concentrations of wear particles. The synthesis of procollagen type I and different cytokines was analysed, and markers for apoptosis and necrosis were also detected. The cytokine synthesis rates in the osteoblasts were initially increased and varied, depending on incubation time and particle concentration. Specific differences in the synthesis rates of interleukin (IL)‑6, IL-8, vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) were observed with the different bone cements examined. The negative effect of the particles on the synthesis of procollagen type I and increased rates of cell apoptosis and necrosis were observed with all three cements analysed. Our present data suggest that wear particles from the interface between the total hip stem and bone cement have a significant effect on viability, cytokine expression and collagen synthesis in human osteoblasts, depending on the bone cement used.

  15. Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway.

    Science.gov (United States)

    Chen, Yan-qing; Zhao, Jing; Jin, Cheng-wei; Li, Yi-hui; Tang, Meng-xiong; Wang, Zhi-hao; Zhang, Wei; Zhang, Yun; Li, Li; Zhong, Ming

    2016-06-01

    Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl- and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin II-induced VSMC senescence and collagen overexpression. In addition, testosterone inhibited angiotensin II-induced matrix metalloproteinase-2 (MMP-2) activity, which played a pivotal role in facilitating age-related collagen deposition. Testosterone increased the expression of tissue inhibitor of metalloproteinase-2 but decreased the expression of MMP-2 and membrane type-1 metalloproteinase which contributed to increase MMP-2 activity. The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation. The effects of testosterone were reversed by a Gas6 blocker, Axl-Fc, and a specific inhibitor of Axl, R428. Treatment of VSMCs with PI3K inhibitor LY294002 abrogated the downregulating effect of testosterone on MMP-2 activity. Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence. Taken together, Gas6/Axl and Akt/FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis. Our results provide a novel mechanism underlying the protective effect of testosterone on vascular aging and may serve as a theoretical basis for testosterone replacement therapy.

  16. Novel synthesis strategy for composite hydrogel of collagen/hydroxyapatite-microsphere originating from conversion of CaCO3 templates.

    Science.gov (United States)

    Wei, Qingrong; Lu, Jian; Wang, Qiaoying; Fan, Hongsong; Zhang, Xingdong

    2015-03-20

    Inspired by coralline-derived hydroxyapatite, we designed a methodological route to synthesize carbonated-hydroxyapatite microspheres from the conversion of CaCO3 spherulite templates within a collagen matrix under mild conditions and thus constructed the composite hydrogel of collagen/hydroxyapatite-microspheres. Fourier transform infrared spectroscopy (FTIR) and x-ray diffraction (XRD) were employed to confirm the successful generation of the carbonated hydroxyapatite phase originating from CaCO3, and the ratios of calcium to phosphate were tracked over time. Variations in the weight portion of the components in the hybrid gels before and after the phase transformation of the CaCO3 templates were identified via thermogravimetric analysis (TGA). Scanning electron microscopy (SEM) shows these composite hydrogels have a unique multiscale microstructure consisting of a collagen nanofibril network and hydroxyapatite microspheres. The relationship between the hydroxyapatite nanocrystals and the collagen fibrils was revealed by transmission electron microscopy (TEM) in detail, and the selected area electron diffraction (SAED) pattern further confirmed the results of the XRD analyses which show the typical low crystallinity of the generated hydroxyapatite. This smart synthesis strategy achieved the simultaneous construction of microscale hydroxyapatite particles and collagen fibrillar hydrogel, and appears to provide a novel route to explore an advanced functional hydrogel materials with promising potentials for applications in bone tissue engineering and reconstruction medicine.

  17. Transcription factor EGR1 directs tendon differentiation and promotes tendon repair

    Science.gov (United States)

    Guerquin, Marie-Justine; Charvet, Benjamin; Nourissat, Geoffroy; Havis, Emmanuelle; Ronsin, Olivier; Bonnin, Marie-Ange; Ruggiu, Mathilde; Olivera-Martinez, Isabel; Robert, Nicolas; Lu, Yinhui; Kadler, Karl E.; Baumberger, Tristan; Doursounian, Levon; Berenbaum, Francis; Duprez, Delphine

    2013-01-01

    Tendon formation and repair rely on specific combinations of transcription factors, growth factors, and mechanical parameters that regulate the production and spatial organization of type I collagen. Here, we investigated the function of the zinc finger transcription factor EGR1 in tendon formation, healing, and repair using rodent animal models and mesenchymal stem cells (MSCs). Adult tendons of Egr1–/– mice displayed a deficiency in the expression of tendon genes, including Scx, Col1a1, and Col1a2, and were mechanically weaker compared with their WT littermates. EGR1 was recruited to the Col1a1 and Col2a1 promoters in postnatal mouse tendons in vivo. Egr1 was required for the normal gene response following tendon injury in a mouse model of Achilles tendon healing. Forced Egr1 expression programmed MSCs toward the tendon lineage and promoted the formation of in vitro–engineered tendons from MSCs. The application of EGR1-producing MSCs increased the formation of tendon-like tissues in a rat model of Achilles tendon injury. We provide evidence that the ability of EGR1 to promote tendon differentiation is partially mediated by TGF-β2. This study demonstrates EGR1 involvement in adult tendon formation, healing, and repair and identifies Egr1 as a putative target in tendon repair strategies. PMID:23863709

  18. The effect of Centella asiatica, vitamins, glycolic acid and their mixtures preparations in stimulating collagen and fibronectin synthesis in cultured human skin fibroblast.

    Science.gov (United States)

    Hashim, Puziah

    2014-03-01

    Centella asiatica (Linn.) Urban is well known in promoting wound healing and provides significant benefits in skin care and therapeutic products formulation. Glycolic acid and vitamins also play a role in the enhancement of collagen and fibronectin synthesis. Here, we evaluate the specific effect of Centella asiatica (CA), vitamins, glycolic acid and their mixture preparations to stimulate collagen and fibronectin synthesis in cultured human fibroblast cells. The fibroblast cells are incubated with CA, glycolic acid, vitamins and their mixture preparations for 48 h. The cell lysates were analyzed for protein content and collagen synthesis by direct binding enzyme immunoassay. The fibronectin of the cultured supernatant was measured by sandwich enzyme immunoassay. The results showed that CA, glycolic acid, vitamins A, E and C significantly stimulate collagen and fibronectin synthesis in the fibroblast. Addition of glycolic acid and vitamins to CA further increased the levels of collagen and fibronectin synthesis to 8.55 and 23.75 μg/100 μg, respectively. CA, glycolic acid, vitamins A, E, and C, and their mixtures demonstrated stimulatory effect on both extra-cellular matrix synthesis of collagen and fibronectin in in vitro studies on human foreskin fibroblasts, which is beneficial to skin care and therapeutic products formulation.

  19. Proline Precursors and Collagen Synthesis: Biochemical Challenges of Nutrient Supplementation and Wound Healing.

    Science.gov (United States)

    Albaugh, Vance L; Mukherjee, Kaushik; Barbul, Adrian

    2017-11-01

    Wound healing is a complex process marked by highly coordinated immune fluxes into an area of tissue injury; these are required for re-establishment of normal tissue integrity. Along with this cascade of cellular players, wound healing also requires coordinated flux through a number of biochemical pathways, leading to synthesis of collagen and recycling or removal of damaged tissues. The availability of nutrients, especially amino acids, is critical for wound healing, and enteral supplementation has been intensely studied as a potential mechanism to augment wound healing-either by increasing tensile strength, decreasing healing time, or both. From a practical standpoint, although enteral nutrient supplementation may seem like a reasonable strategy to augment healing, a number of biochemical and physiologic barriers exist that limit this strategy. In this critical review, the physiology of enteral amino acid metabolism and supplementation and challenges therein are discussed in the context of splanchnic physiology and biochemistry. Additionally, a review of studies examining various methods of amino acid supplementation and the associated effects on wound outcomes are discussed. © 2017 American Society for Nutrition.

  20. Oriented Collagen Scaffolds for Tissue Engineering

    OpenAIRE

    Shohta Kodama; Taro Saku; Hiroshi Mikami; Go Kuwahara; Toru Kosaka; Yoshihiro Isobe

    2012-01-01

    Oriented collagen scaffolds were developed in the form of sheet, mesh and tube by arraying flow-oriented collagen string gels and dehydrating the arrayed gels. The developed collagen scaffolds can be any practical size with any direction of orientation for tissue engineering applications. The birefringence of the collagen scaffolds was quantitatively analyzed by parallel Nicols method. Since native collagen in the human body has orientations such as bone, cartilage, tendon and cornea, and the...

  1. Endocytic collagen degradation

    DEFF Research Database (Denmark)

    Madsen, Daniel H.; Jürgensen, Henrik J.; Ingvarsen, Signe Ziir

    2012-01-01

    it crucially important to understand both the collagen synthesis and turnover mechanisms in this condition. Here we show that the endocytic collagen receptor, uPARAP/Endo180, is a major determinant in governing the balance between collagen deposition and degradation. Cirrhotic human livers displayed a marked...

  2. Pyropia yezoensis peptide promotes collagen synthesis by activating the TGF-β/Smad signaling pathway in the human dermal fibroblast cell line Hs27.

    Science.gov (United States)

    Kim, Cho-Rong; Kim, Young-Min; Lee, Min-Kyeong; Kim, In-Hye; Choi, Youn-Hee; Nam, Taek-Jeong

    2017-01-01

    Pyropia yezoensis (P. yezoensis) is a marine algae that exhibits antioxidant, anti-inflammatory, antitumor and anti-aging activities. In this study, we investigated the effects of the P. yezoensis peptide, PYP1‑5, on collagen synthesis in the human dermal fibroblast cell line Hs27. Skin aging is related to reduced collagen production and the activities of multiple enzymes, including matrix metalloproteinases (MMPs), which degrade collagen structure in the dermis, and tissue inhibitor of tissue inhibitor of metalloproteinases (TIMPs), which inhibit the action of MMPs. While collagen synthesis is associated with a number of signaling pathways, we examined the increased collagen synthesis via the upregulation of the transforming growth factor-β (TGF-β)/Smad signaling pathway. Using MTS assay, we found that PYP1‑5 did not affect cell viability. Moreover, we confirmed that PYP1‑5 increased type 1 collagen expression using enzyme-linked immunosorbent assay (ELISA), western blot analysis and quantitative PCR. In addition, we identified changes in various enzymes, as well as the mechanisms behind the PYP1‑5-induced collagen synthesis. PYP1‑5 decreased the MMP-1 protein and mRNA levels, and increased the TIMP-1 and TIMP-2 protein and mRNA levels. In addition, PYP1‑5 activated the TGF-β/Smad signaling pathway, which increased TGF-β1, p-Smad2 and p-Smad3 expression, while inhibiting Smad7, an inhibitor of the TGF-β/Smad pathway. Furthermore, PYP1‑5 upregulated transcription factor specificity protein 1 (Sp1) expression, which is reportedly involved in type 1 collagen expression. These findings indicate that PYP1‑5 activates the TGF-β/Smad signaling pathway, which subsequently induces collagen synthesis in Hs27 cells.

  3. Type I Collagen Synthesis Marker Procollagen I N-Terminal Peptide (PINP) in Prostate Cancer Patients Undergoing Intermittent Androgen Suppression

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Gerhard, E-mail: gerhard.hamilton@toc.lbg.ac.at; Olszewski-Hamilton, Ulrike [Ludwig Boltzmann Cluster of Translational of Oncology, Nussdorfer Strasse 64, Vienna A-1090 (Austria); Theyer, Gerhard [Hospital Kittsee, Kittsee A-2421, Burgenland (Austria)

    2011-09-15

    Intermittent androgen suppression (IAS) therapy for prostate cancer patients attempts to maintain the hormone dependence of the tumor cells by cycles alternating between androgen suppression (AS) and treatment cessation till a certain prostate-specific antigen (PSA) threshold is reached. Side effects are expected to be reduced, compared to standard continuous androgen suppression (CAS) therapy. The present study examined the effect of IAS on bone metabolism by determinations of serum procollagen I N-terminal peptide (PINP), a biochemical marker of collagen synthesis. A total of 105 treatment cycles of 58 patients with prostate cancer stages ≥pT2 was studied assessing testosterone, PSA and PINP levels at monthly intervals. During phases of AS lasting for up to nine months PSA levels were reversibly reduced, indicating apoptotic regression of the prostatic tumors. Within the first cycle PINP increased at the end of the AS period and peaked in the treatment cessation phase. During the following two cycles a similar pattern was observed for PINP, except a break in collagen synthesis as indicated by low PINP levels in the first months off treatment. Therefore, measurements of the serum PINP concentration indicated increased bone matrix synthesis in response to >6 months of AS, which uninterruptedly continued into the first treatment cessation phase, with a break into each of the following two pauses. In summary, synthesis of bone matrix collagen increases while degradation decreases during off-treatment phases in patients undergoing IAS. Although a direct relationship between bone matrix turnover and risk of fractures is difficult to establish, IAS for treatment of biochemical progression of prostate tumors is expected to reduce osteoporosis in elderly men often at high risk for bone fractures representing a highly suitable patient population for this kind of therapy.

  4. Type III collagen can be present on banded collagen fibrils regardless of fibril diameter

    OpenAIRE

    1987-01-01

    Monoclonal antibodies that recognize an epitope within the triple helix of type III collagen have been used to examine the distribution of that collagen type in human skin, cornea, amnion, aorta, and tendon. Ultrastructural examination of those tissues indicates antibody binding to collagen fibrils in skin, amnion, aorta, and tendon regardless of the diameter of the fibril. The antibody distribution is unchanged with donor age, site of biopsy, or region of tissue examined. In contrast, antibo...

  5. Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Kairui; Zhang, Sheng [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Li, Qianqian [Cancer Research Institute, Southern Medical University, Guangzhou 510515 (China); Yang, Jun [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Department of Orthopaedics, 421 Hospital of PLA, Guangzhou 510318 (China); Dong, Weiqiang [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Department of Orthopaedics, The First Affiliated Hospital to Guangzhou Medical University, Guangzhou 510120 (China); Wang, Shengnan; Cheng, Yirong; Al-Qwbani, Mohammed [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Wang, Qiang, E-mail: 1780468505@qq.com [Department of Orthopaedics, Subei People’s Hospital of Jiangsu Province (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu Province 225001 (China); Yu, Bin, E-mail: carryzhang1985@live.com [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China)

    2014-07-18

    Highlights: • Celecoxib has no effects on TDSCs cell proliferation in various concentrations. • Celecoxib reduced mRNAs levels of tendon associated transcription factor. • Celecoxib reduced mRNAs levels of main tendon associated collagen. • Celecoxib reduced mRNAs levels of tendon associated molecules. - Abstract: NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 μg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p > 0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation.

  6. Flexor tendon physiology: tendon nutrition and cellular activity in injury and repair.

    Science.gov (United States)

    Gelberman, R H

    1985-01-01

    Scientific studies of the past 20 years have done much to redefine the mechanisms by which flexor tendons heal. Several points have become increasingly clear: Flexor tendons are nourished to a greater extent by synovial fluid diffusion than vascular perfusion. Tendon cells are capable of proliferating, producing collagen, and reconstructing their own gliding surface in the absence of adhesion ingrowth. The key to a successful outcome after flexor tendon repair appears to be an early restoration of tendon continuity, reconstruction of the sheath, if possible, and early passive mobilization. This complex stimulates the tendon's intrinsic repair potential, which is contained within the cells of the tendon itself but appears to be expressed only under ideal experimental and clinical situations.

  7. Localization and synthesis of collagen types III and V during remodelling and decidualization in rat uterus.

    Science.gov (United States)

    Hurst, P R; Palmay, R D; Myers, D B

    1997-01-01

    Uteri of pregnant rats on Days 6, 7 and 8 of pregnancy were studied to determine the histochemical distribution of collagen types III and V and the incorporation of [3H]glycine into fibrillar collagens during the period of embryonic implantation. Types III and V had a similar distribution in the non-decidual stromal region and muscle layers in implantation sites. They were found to have very low levels in the primary decidual tissue on Day 6 and were not detected in developing decidual tissues on Days 7 or 8. Following injection of labelled glycine, collagen was extracted and the specific activity of the collagens determined by fluorography and 3H incorporated into the collagen bands in the gels. It was found that incorporation of label into both types I and III was similar (33.4+/-12.0 and 31.8+/-18.1 cpm microg-1 collagen respectively) but 3.5 times that of type V (7.7+/-5.3 cpm microg-1). These studies suggest that although fibrillar collagens are metabolized or redistributed in the growing decidual tissue, they are incorporated rapidly into the extracellular matrix during remodelling of the outer stroma and muscle tissues.

  8. Benzo[a]pyrene/aryl hydrocarbon receptor signaling inhibits osteoblastic differentiation and collagen synthesis of human periodontal ligament cells.

    Science.gov (United States)

    Monnouchi, S; Maeda, H; Yuda, A; Serita, S; Wada, N; Tomokiyo, A; Akamine, A

    2016-12-01

    Cigarette smoking has detrimental effects on periodontal tissue, and is known to be a risk factor for periodontal disease, including the loss of alveolar bone and ligament tissue. However, the direct effects of cigarette smoking on periodontal tissue remain unclear. Recently, we demonstrated that benzo[a]pyrene (BaP), which is a prototypic member of polycyclic aryl hydrocarbons and forms part of the content of cigarettes, attenuated the expression of extracellular matrix remodeling-related genes in human periodontal ligament (PDL) cells (HPDLCs). Thus, we aimed to examine the effects of BaP on the osteoblastic differentiation and collagen synthesis of HPDLCs. HPDLCs were obtained from healthy molars of three patients, and quantitative reverse transcription-polymerase chain reaction were performed for gene expression analyses of cytochrome P450 1A1 and 1B1, alkaline phosphatase, bone sialoprotein and aryl hydrocarbon receptor (AhR), a receptor for polycyclic aryl hydrocarbons. We have also analyzed the role of the AhR, using 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191), which is an AhR antagonist. The treatment of HPDLCs with BaP reduced mRNA expression of osteogenic genes, alkaline phosphatase activity, mineralization and collagen synthesis. The treatment with CH-223191 subsequently restored the observed suppressive effects of BaP on HPDLCs. The present results suggest that BaP exerts inhibitory effects on the maintenance of homeostasis in HPDL tissue, such as osteoblastic differentiation and collagen synthesis of HPDLCs, and that this signaling pathway could be suppressed by preventing the transactivity of AhR. Future studies may unveil a role for the inhibition of AhR as a promising therapeutic agent for periodontal disease caused by cigarette smoking. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Christensen, M K; Wachtell, K

    2005-01-01

    Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy...

  10. Investigating tendon mineralisation in the avian hindlimb: a model for tendon ageing, injury and disease

    Science.gov (United States)

    Agabalyan, Natacha A; Evans, Darrell J R; Stanley, Rachael L

    2013-01-01

    Mineralisation of the tendon tissue has been described in various models of injury, ageing and disease. Often resulting in painful and debilitating conditions, the processes underlying this mechanism are poorly understood. To elucidate the progression from healthy tendon to mineralised tendon, an appropriate model is required. In this study, we describe the spontaneous and non-pathological ossification and calcification of tendons of the hindlimb of the domestic chicken (Gallus gallus domesticus). The appearance of the ossified avian tendon has been described previously, although there have been no studies investigating the developmental processes and underlying mechanisms leading to the ossified avian tendon. The tissue and cells from three tendons – the ossifying extensor and flexor digitorum longus tendons and the non-ossifying Achilles tendon – were analysed for markers of ageing and mineralisation using histology, immunohistochemistry, cytochemistry and molecular analysis. Histologically, the adult tissue showed a loss of healthy tendon crimp morphology as well as markers of calcium deposits and mineralisation. The tissue showed a lowered expression of collagens inherent to the tendon extracellular matrix and presented proteins expressed by bone. The cells from the ossified tendons showed a chondrogenic and osteogenic phenotype as well as tenogenic phenotype and expressed the same markers of ossification and calcification as the tissue. A molecular analysis of the gene expression of the cells confirmed these results. Tendon ossification within the ossified avian tendon seems to be the result of an endochondral process driven by its cells, although the roles of the different cell populations have yet to be elucidated. Understanding the role of the tenocyte within this tissue and the process behind tendon ossification may help us prevent or treat ossification that occurs in injured, ageing or diseased tendon. PMID:23826786

  11. Synthesis and Characterization of Collagen Scaffolds Reinforced by Eggshell Derived Hydroxyapatite for Tissue Engineering.

    Science.gov (United States)

    Padmanabhan, Sanosh Kunjalukkal; Salvatore, Luca; Gervaso, Francesca; Catalano, Massimo; Taurino, Antonietta; Sannino, Alessando; Licciulli, Antonio

    2015-01-01

    In this work, we synthesized porous nanohydroxyapatite/collagen composite scaffold (nHA-COL), which resemble extracellular matrices in bone and cartilage tissues. Nano hydroxyapatite (nHA) was successfully nucleated in to the collagen matrix using hen eggshell as calcium biogenic source. Porosity was evaluated by apparent and theoretical density measurement. Porosity of all scaffolds was in the range of 95-98%. XRD and TEM analyses show the purity and size of nucleated HA around 10 nm and selected area electron diffraction (SAED) analysis reveals the polycrystalline nature of nucleated HA. SEM analysis reveals (i) all the scaffolds have interconnected pores with an average pore diameter of 130 micron and (ii) aggregates of hydroxyapatite were strongly embedded in the collagen matrix for both composite scaffolds compared with pure collagen scaffold. EDS analysis shows the Ca/P stoichiometric ratio around 1.67 and FTIR reveals the chemical interaction between the collagen molecule and HA particles. The testing of mechanical properties evidenced that incorporation of HA resulted in up to a two-fold increase in compressive modulus with high reinforcement level (-7 kPa for 50HA-50COL) compared to pure collagen scaffold.

  12. Dexamethasone alters messenger RNA levels but not synthesis of collagens, fibronectin, or laminin by cultured rat fat-storing cells.

    Science.gov (United States)

    Niki, T; Schuppan, D; de Bleser, P J; Vrijsen, R; Pipeleers-Marichal, M; Beyaert, R; Wisse, E; Geerts, A

    1996-06-01

    Glucocorticoids have been shown to suppress collagen synthesis and gene expression by fibroblasts. However, little is known about their effects on fat-storing cells, the major matrix-producing cells in liver fibrosis. In this study we investigated the effect of dexamethasone on the extracellular matrix expression by cultured rat fat-storing cells. Fat-storing cells were isolated from male Wistar rats by collagenase/pronase digestion and purified by density gradient centrifugation. Fat-storing cells in early primary culture (3-day-old, representing a relatively quiescent phenotype) and in subculture (one passage, about 2-week-old, representing an activated phenotype) were treated with 10(-6) mol/L dexamethasone for messenger RNA (mRNA) study or with 10(-8) to 10(-6) mol/L dexamethasone for protein study. Expression of collagen type I, III, IV, fibronectin, and laminin was analyzed at the mRNA level by Northern hybridization, and at the protein level by metabolic labeling and immunoprecipitation. Dexamethasone had a variable effect on the expression of collagen alpha1(I) mRNA level. While a tendency for modest suppression was observed (5%-50%) in primary cells, the difference was not statistically significant. Variable response was observed in subcultured cells. Collagen alpha1(III) mRNA level showed a tendency for stimulation. Dexamethasone stimulated the expression of collagen alpha1 (IV), fibronectin, and laminin B1 mRNA levels by 1.4-, 2.4-, and 1.6-fold respectively, in primary fat-storing cells. Subcultured cells showed a similar response, but the magnitude of stimulation was more variable than that of primary cells. Unexpectedly, at the protein level dexamethasone had no effect on the expression of these proteins. Our results indicate that glucocorticoids do not possess a net suppressive effect on extracellular matrix synthesis by fat-storing cells. Beneficial effects of glucocorticoids may be attributable to other mechanisms of action, such as their anti

  13. Release of tensile strain on engineered human tendon tissue disturbs cell adhesions, changes matrix architecture, and induces an inflammatory phenotype

    DEFF Research Database (Denmark)

    Bayer, Monika L; Schjerling, Peter; Herchenhan, Andreas

    2014-01-01

    -inflammatory mediators and tendon phenotypic specific molecules, in an in vitro model where tendon-like tissue was engineered from human tendon cells. Tissue sampling was performed 1, 2, 4 and 6 days after surgical de-tensioning of the tendon construct. When tensile stimulus was removed, integrin type collagen receptors...

  14. Nutrition of cruciate ligament reconstruction by diffusion. Collagen synthesis studied in rabbits.

    Science.gov (United States)

    Amiel, D; Akeson, W H; Renzoni, S; Harwood, F; Abel, M

    1986-06-01

    The reconstructed anterior cruciate ligament was studied in the rabbit using the medial third of the patellar tendon. Tritiated proline, 100 microCi/kg body weight, was injected intra-articularly to insure detection of the metabolic conversion product 3H-hydroxyproline in the avascular graft. During the immediate postoperative period, nutrients were found to derive from the synovial fluid through a process of diffusion, demonstrating that synovial nutrition occurs prior to revascularization of the graft.

  15. Doxazosin stimulates galectin-3 expression and collagen synthesis in HL-1 cardiomyocytes independent of protein kinase C pathway

    Directory of Open Access Journals (Sweden)

    Xiaoqian Qian

    2016-12-01

    Full Text Available Doxazosin, a drug commonly prescribed for hypertension and prostate disease, increases heart failure risk. However, the underlying mechanism remains unclear. Galectin-3 is an important mediator that plays a pathogenic role in cardiac hypertrophy and heart failure. In the present study, we investigated whether doxazosin could stimulate galectin-3 expression and collagen synthesis in cultured HL-1 cardiomyocytes. We found that doxazosin dose-dependently induced galectin-3 protein expression, with a statistically significant increase in expression with a dose as low as 0.01 μM. Doxazosin upregulated collagen I and α-smooth muscle actin (α-SMA protein levels and also induced apoptotic protein caspase-3 in HL-1 cardiomyocytes. Although we previously reported that activation of protein kinase C (PKC stimulates galectin-3 expression, blocking the PKC pathway with the PKC inhibitor chelerythrine did not prevent doxazosin-induced galectin-3 and collagen expression. Consistently, doxazosin treatment did not alter total and phosphorylated PKC. These results suggest that doxazosin-stimulated galectin-3 is independent of PKC pathway. To determine if the α1-adrenergic pathway is involved, we pretreated the cells with the irreversible α-adrenergic receptor blocker phenoxybenzamine and found that doxazosin-stimulated galectin-3 and collagen expression was similar to controls, suggesting that doxazosin acts independently of α1-adrenergic receptor blockade. Collectively, we show a novel effect of doxazosin on cardiomycytes by stimulating heart fibrosis factor galectin-3 expression. The mechanism of action of doxazosin is not mediated through either activation of the PKC pathway or antagonism of α1-adrenergic receptors.

  16. Collagen synthesis promoting pullulan-PEI-ascorbic acid conjugate as an efficient anti-cancer gene delivery vector.

    Science.gov (United States)

    Ambattu, Lizebona August; Rekha, M R

    2015-08-01

    Cationized pullulan (pullulan-PEI; PP) was synthesized and further modified with an anti-oxidant molecule, ascorbic acid (PPAA) at various ratios. The nanoplexes formed at an optimum ratio of 4:1 was within a size of 150nm and had a zeta potential of 9-14mV. The nanoplexes at this ratio was used for further investigations. The cell internalization and transfection efficiency of these nanoplexes were determined in presence of serum. The internalization and transfection efficiency were found to be unaffected by the presence of fetal bovine serum. Another interesting observation was that this polymer was found to have collagen synthesis promoting property. The collagen synthesis effect of these polymers was quantified and observed that PPAA3 promoted the highest. Transfection efficiency was evaluated by assessing the p53 gene expression in C6 rat glioma cells and cell death was quantified to be 96% by flow cytometry, thus establishing the high efficacy of this polymer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors

    Science.gov (United States)

    Diop-Frimpong, Benjamin; Chauhan, Vikash P.; Krane, Stephen; Boucher, Yves; Jain, Rakesh K.

    2011-01-01

    The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan—a clinically approved angiotensin II receptor antagonist with noted antifibrotic activity—can enhance the penetration and efficacy of nanomedicine. We found that losartan inhibited collagen I production by carcinoma-associated fibroblasts isolated from breast cancer biopsies. Additionally, it led to a dose-dependent reduction in stromal collagen in desmoplastic models of human breast, pancreatic, and skin tumors in mice. Furthermore, losartan improved the distribution and therapeutic efficacy of intratumorally injected oncolytic herpes simplex viruses. Finally, it also enhanced the efficacy of i.v. injected pegylated liposomal doxorubicin (Doxil). Thus, losartan has the potential to enhance the efficacy of nanotherapeutics in patients with desmoplastic tumors. PMID:21282607

  18. Water-filtered near-infrared influences collagen synthesis of keloid-fibroblasts in contrast to normal foreskin fibroblasts.

    Science.gov (United States)

    Zöller, Nadja; König, Anke; Butting, Manuel; Kaufmann, Roland; Bernd, August; Valesky, Eva; Kippenberger, Stefan

    2016-10-01

    Hypertrophic scar development is associated to impaired wound healing, imbalanced fibroblast proliferation and extracellular matrix synthesis. Stigmatization, physical restrictions and high recurrence rates are only some aspects that illustrate the severe influence impaired wound healing can have on patients' life. The treatment of hypertrophic scars especially keloids is still a challenge. In recent years water-filtered near-infrared irradiation (wIRA) composed of near-infrared (NIR) and a thermal component is applied for an increasing penal of clinical purposes. It is described to beneficially influence e.g. wound healing. But discrimination between the thermal and the NIR dependent components of these effects has not been conclusively elucidated. Aim of our study was therefore to investigate the influence of the light fraction on the thermal impact of wIRA irradiation in dermal cells. We concentrated our analysis on morphological properties and collagen synthesis. Foreskin fibroblasts and the keloid fibroblast cell line KF111 were exposed to temperatures between 37°C and 46°C with or without additional irradiation with 360J/cm(2) NIR. Our results show that viability was not influenced by irradiation. Independent of the analysed fibroblast species temperature dependent occurrence of spheric cells could be observed. These morphological changes were clearly counteracted by additional light exposure. Convective heat reduced collagen type I synthesis in both cell species depending on the applied temperature. Co-treatment with NIR significantly reversed this effect in keloid fibroblast cultures treated at 46°C whereas no difference could be observed in the foreskin fibroblasts. The observed influence on collagen type I synthesis was associated to a temperature dependent TGF-β1 secretion reduction. Co-stimulation of keloid cultures with NIR at 46°C completely abolished the temperature dependent TGF-β1 secretion reduction. In foreskin fibroblast cultures co

  19. Oriented Collagen Scaffolds for Tissue Engineering

    Science.gov (United States)

    Isobe, Yoshihiro; Kosaka, Toru; Kuwahara, Go; Mikami, Hiroshi; Saku, Taro; Kodama, Shohta

    2012-01-01

    Oriented collagen scaffolds were developed in the form of sheet, mesh and tube by arraying flow-oriented collagen string gels and dehydrating the arrayed gels. The developed collagen scaffolds can be any practical size with any direction of orientation for tissue engineering applications. The birefringence of the collagen scaffolds was quantitatively analyzed by parallel Nicols method. Since native collagen in the human body has orientations such as bone, cartilage, tendon and cornea, and the orientation has a special role for the function of human organs, the developed various types of three-dimensional oriented collagen scaffolds are expected to be useful biomaterials for tissue engineering and regenerative medicines. PMID:28817059

  20. Oriented Collagen Scaffolds for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Shohta Kodama

    2012-03-01

    Full Text Available Oriented collagen scaffolds were developed in the form of sheet, mesh and tube by arraying flow-oriented collagen string gels and dehydrating the arrayed gels. The developed collagen scaffolds can be any practical size with any direction of orientation for tissue engineering applications. The birefringence of the collagen scaffolds was quantitatively analyzed by parallel Nicols method. Since native collagen in the human body has orientations such as bone, cartilage, tendon and cornea, and the orientation has a special role for the function of human organs, the developed various types of three-dimensional oriented collagen scaffolds are expected to be useful biomaterials for tissue engineering and regenerative medicines.

  1. Oriented Collagen Scaffolds for Tissue Engineering.

    Science.gov (United States)

    Isobe, Yoshihiro; Kosaka, Toru; Kuwahara, Go; Mikami, Hiroshi; Saku, Taro; Kodama, Shohta

    2012-03-16

    Oriented collagen scaffolds were developed in the form of sheet, mesh and tube by arraying flow-oriented collagen string gels and dehydrating the arrayed gels. The developed collagen scaffolds can be any practical size with any direction of orientation for tissue engineering applications. The birefringence of the collagen scaffolds was quantitatively analyzed by parallel Nicols method. Since native collagen in the human body has orientations such as bone, cartilage, tendon and cornea, and the orientation has a special role for the function of human organs, the developed various types of three-dimensional oriented collagen scaffolds are expected to be useful biomaterials for tissue engineering and regenerative medicines.

  2. Synthesis and Fabrication of Nanocomposite Fibers of Collagen-Cellulose Nanocrystals by Coelectrocompaction.

    Science.gov (United States)

    Cudjoe, Elvis; Younesi, Mousa; Cudjoe, Edward; Akkus, Ozan; Rowan, Stuart J

    2017-04-10

    An electrochemical process has been used to compact cellulose nanocrystals (CNC) and access aligned micron-sized CNC fibers. Placing a current across aqueous solutions of carboxylic acid functionalized CNCs (t-CNC-COOH) or carboxylic acid/primary amine functionalized CNCs (t-CNC-COOH-NH2) creates a pH gradient between the electrodes, which results in the migration and concentration of the CNC fibers at their isoelectric point. By matching the carboxylic acid/amine ratio of CNCs and collagen (ca. 30:70 carboxylic acid:amine ratio), it is possible to coelectrocompact both nanofibers and access aligned nanocomposite fibers. t-CNC-COOH-NH2/collagen fibers showed a maximum increase in mechanical properties at 5 wt % of t-CNC-COOH-NH2. Compared to collagen/CNC films which have no alignment in the plane of the films, the tensile properties of the aligned fibers show a significant enhancement in the wet mechanical properties (40 MPa vs 230 MPa) for the 5 wt % of t-CNC-COOH-NH2/collagen films and fiber, respectively.

  3. Tendon Vasculature in Health and Disease

    Science.gov (United States)

    Tempfer, Herbert; Traweger, Andreas

    2015-01-01

    Tendons represent a bradytrophic tissue which is poorly vascularized and, compared to bone or skin, heal poorly. Usually, a vascularized connective scar tissue with inferior functional properties forms at the injury site. Whether the increased vascularization is the root cause of tissue impairments such as loss of collagen fiber orientation, ectopic formation of bone, fat or cartilage, or is a consequence of these pathological changes remains unclear. This review provides an overview of the role of tendon vasculature in healthy and chronically diseased tendon tissue as well as its relevance for tendon repair. Further, the nature and the role of perivascular tendon stem/progenitor cells residing in the vascular niche will be discussed and compared to multipotent stromal cells in other tissues. PMID:26635616

  4. Rational basis for oligodeoxynucleotides to inhibit collagen synthesis in lung fibroblasts and primary fibroblasts from liver granulomas of Schistosoma mansoni-infected mice.

    Science.gov (United States)

    Cutroneo, Kenneth R; Boros, Dov L

    2002-06-28

    Hepatocellular carcinoma is associated with liver fibrosis. Murine schistosomiasis infection offers a model to study hepatic fibrogenesis. Single-stranded phosphorothiate oligodeoxynucleotides containing the TGF-beta regulatory element have been shown to regulate the transcription of this gene and effectively inhibit collagen synthesis in primary fibroblasts isolated from schistosomiasis-induced hepatic granulomas. While the single-stranded oligos did not decrease collagen and non-collagen protein synthesis below control levels, their double-stranded modified and unmodified counterparts did. Competitive cold oligodeoxynucleotide gel mobility shift analysis using control fibroblast nuclear extract demonstrated that the single-stranded oligos diminished binding of the TGF-beta activator protein to the TGF-beta regulatory element while the double-stranded oligos totally inhibited this binding. TGF-beta element containing single-stranded phosphorothioate oligodeoxynucleotides and their double-stranded counterparts may be successful therapeutic agents to inhibit hepatic fibrogenesis and associated hepatocellular carcinoma.

  5. The effect of decellularized matrices on human tendon stem/progenitor cell differentiation and tendon repair.

    Science.gov (United States)

    Yin, Zi; Chen, Xiao; Zhu, Ting; Hu, Jia-jie; Song, Hai-xin; Shen, Wei-liang; Jiang, Liu-yun; Heng, Boon Chin; Ji, Jun-feng; Ouyang, Hong-Wei

    2013-12-01

    It is reported that decellularized collagen matrices derived from dermal skin and bone have been clinically used for tendon repair. However, the varying biological and physical properties of matrices originating from different tissues may influence the differentiation of tendon stem cells, which has not been systematically evaluated. In this study, the effects of collagenous matrices derived from different tissues (tendon, bone and dermis) on the cell differentiation of human tendon stem/progenitor cells (hTSPCs) were investigated, in the context of tendon repair. It was found that all three matrices supported the adhesion and proliferation of hTSPCs despite differences in topography. Interestingly, tendon-derived decellularized matrix promoted the tendinous phenotype in hTSPCs and inhibited their osteogenesis, even under osteogenic induction conditions, through modulation of the teno- and osteolineage-specific transcription factors Scleraxis and Runx2. Bone-derived decellularized matrix robustly induced osteogenic differentiation of hTSPCs, whereas dermal skin-derived collagen matrix had no apparent effect on hTSPC differentiation. Based on the specific biological function of the tendon-derived decellularized matrix, a tissue-engineered tendon comprising TSPCs and tendon-derived matrix was successfully fabricated for Achilles tendon reconstruction. Implantation of this cell-scaffold construct led to a more mature structure (histology score: 4.08 ± 0.61 vs. 8.51 ± 1.66), larger collagen fibrils (52.2 ± 1.6 nm vs. 47.5 ± 2.8 nm) and stronger mechanical properties (stiffness: 21.68 ± 7.1 Nm m(-1) vs.13.2 ± 5.9 Nm m(-1)) of repaired tendons compared to the control group. The results suggest that stem cells promote the rate of repair of Achilles tendon in the presence of a tendinous matrix. This study thus highlights the potential of decellularized matrix for future tissue engineering applications, as well as developing a practical strategy for functional tendon

  6. Influence of Biodentine® - A Dentine Substitute - On Collagen Type I Synthesis in Pulp Fibroblasts In Vitro.

    Directory of Open Access Journals (Sweden)

    Frangis Nikfarjam

    Full Text Available Preserving a patient's own teeth-even in a difficult situation-is nowadays preferable to surgical intervention and therefore promotes development of suitable dental repair materials. Biodentine®, a mineral trioxide aggregate substitute, has been used to replace dentine in a bioactive and biocompatible manner in both the dental crown and the root. The aim of our study was to evaluate the influence of Biodentine® on pulp fibroblasts in vitro. For this study, one to five Biodentine® discs with a diameter of 5.1mm were incubated in DMEM. To obtain Biodentine® suspensions the media were collected and replaced with fresh medium every 24h for 4 days. Primary pulp cells were isolated from freshly extracted wisdom teeth of 20-23 year old patients and incubated with the Biodentine® suspensions. Proliferation, cell morphology, cell integrity and cell viability were monitored. To evaluate the effect of Biodentine® on collagen type I synthesis, the secretion of the N-terminal domain of pro-collagen type I (P1NP and the release of transforming growth factor-β1 (TGF-β1 were quantified. None of the Biodentine® suspensions tested influenced cell morphology, proliferation or cell integrity. The cell viability varied slightly depending on the suspension used. However, the concentrations of P1NP of all pulp fibroblast cultures treated for 24h with the moderate to high Biodentine® concentration containing suspensions of day 1 were reduced to 5% of the control. Furthermore, a significant TGF-β1 reduction was observed after treatment with these suspensions. It could be shown that Biodentine® is biocompatible. However, dissolved particles of the moderate to high concentrated Biodentine® suspensions 24h after mixing induce a significant reduction of TGF-β1 release and reduce the secretion of collagen type I of primary pulp fibroblasts.

  7. Influence of Biodentine® - A Dentine Substitute - On Collagen Type I Synthesis in Pulp Fibroblasts In Vitro.

    Science.gov (United States)

    Nikfarjam, Frangis; Beyer, Kim; König, Anke; Hofmann, Matthias; Butting, Manuel; Valesky, Eva; Kippenberger, Stefan; Kaufmann, Roland; Heidemann, Detlef; Bernd, August; Zöller, Nadja Nicole

    2016-01-01

    Preserving a patient's own teeth-even in a difficult situation-is nowadays preferable to surgical intervention and therefore promotes development of suitable dental repair materials. Biodentine®, a mineral trioxide aggregate substitute, has been used to replace dentine in a bioactive and biocompatible manner in both the dental crown and the root. The aim of our study was to evaluate the influence of Biodentine® on pulp fibroblasts in vitro. For this study, one to five Biodentine® discs with a diameter of 5.1mm were incubated in DMEM. To obtain Biodentine® suspensions the media were collected and replaced with fresh medium every 24h for 4 days. Primary pulp cells were isolated from freshly extracted wisdom teeth of 20-23 year old patients and incubated with the Biodentine® suspensions. Proliferation, cell morphology, cell integrity and cell viability were monitored. To evaluate the effect of Biodentine® on collagen type I synthesis, the secretion of the N-terminal domain of pro-collagen type I (P1NP) and the release of transforming growth factor-β1 (TGF-β1) were quantified. None of the Biodentine® suspensions tested influenced cell morphology, proliferation or cell integrity. The cell viability varied slightly depending on the suspension used. However, the concentrations of P1NP of all pulp fibroblast cultures treated for 24h with the moderate to high Biodentine® concentration containing suspensions of day 1 were reduced to 5% of the control. Furthermore, a significant TGF-β1 reduction was observed after treatment with these suspensions. It could be shown that Biodentine® is biocompatible. However, dissolved particles of the moderate to high concentrated Biodentine® suspensions 24h after mixing induce a significant reduction of TGF-β1 release and reduce the secretion of collagen type I of primary pulp fibroblasts.

  8. Optimizing an Intermittent Stretch Paradigm Using ERK1/2 Phosphorylation Results in Increased Collagen Synthesis in Engineered Ligaments

    Science.gov (United States)

    Paxton, Jennifer Z.; Hagerty, Paul; Andrick, Jonathan J.

    2012-01-01

    Dynamic mechanical input is believed to play a critical role in the development of functional musculoskeletal tissues. To study this phenomenon, cyclic uniaxial mechanical stretch was applied to engineered ligaments using a custom-built bioreactor and the effects of different stretch frequency, amplitude, and duration were determined. Stretch acutely increased the phosphorylation of p38 (3.5±0.74-fold), S6K1 (3.9±0.19-fold), and ERK1/2 (2.45±0.32-fold). The phosphorylation of ERK1/2 was dependent on time, rather than on frequency or amplitude, within these constructs. ERK1/2 phosphorylation was similar following stretch at frequencies from 0.1 to 1 Hz and amplitudes from 2.5% to 15%, whereas phosphorylation reached maximal levels at 10 min of stretch and returned toward basal within 60 min of stretch. Following a single 10-min bout of cyclic stretch, the cells remained refractory to a second stretch for up to 6 h. Using the phosphorylation of ERK1/2 as a guide, the optimum stretch paradigm was hypothesized to be 10 min of stretch at 2.5% of resting length repeated every 6 h. Consistent with this hypothesis, 7 days of stretch using this optimized intermittent stretch program increased the collagen content of the grafts more than a continuous stretch program (CTL=3.1%±0.44%; CONT=4.8%±0.30%; and INT=5.9%±0.56%). These results suggest that short infrequent bouts of loading are optimal for improving engineered tendon and ligament physiology. PMID:21902469

  9. In vitro evaluation of cell proliferation and collagen synthesis on titanium following plasma electrolytic oxidation.

    Science.gov (United States)

    Whiteside, Paul; Matykina, Endzhe; Gough, Julie E; Skeldon, Peter; Thompson, George E

    2010-07-01

    Titania-based coatings produced by plasma electrolytic oxidation are being investigated as bioactive surfaces for titanium implants. In this study, plasma electrolytic oxidation was performed in calcium- and phosphorus-based electrolytes under DC conditions, resulting in coatings of thickness of approximately 8-15 mum. Coating morphologies, microstructures, and compositions were examined by scanning electron microscopy with energy-dispersive X-ray analysis, X-ray diffraction, and electron probe microanalysis. The coatings revealed a cratered morphology, with incorporated calcium and phosphorus species. Proliferation rates of primary human osteoblasts cells on the coatings were up to approximately 37% faster than those for uncoated titanium and 316L stainless steel reference materials. Further, the coatings assisted cell adhesion and generation and anchorage of collagen. The amount of collagen was upto approximately 2.4 times greater than for the reference substrates. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

  10. [Effects and mechanism of allogeneic platelet rich plasma on collagen synthesis in wound healing].

    Science.gov (United States)

    Chen, F C; Chen, M C; Yan, T T; Hou, J J; Yang, J G

    2017-04-01

    Objective: To investigate the effects and mechanism of allogeneic platelet rich plasma (PRP) on collagen in wound surface at different time. Methods: A total of 50 clean 7-week rats were selected for this study, including 10 rats for platelet-rich blood plasma preparation, 20 rats for PRP group and 20 rats for control group, 0.1 ml allogenic PRP and 0.1 ml saline were smeared respectively on wound surfaces of PRP and control group, wound regeneration and healing were examined. Cellular and histological morphology alteration was observed via Masson staining, type Ⅰ and type Ⅲ collagen protein and mRNA expression level were detected by Western blot and real-time PCR. T test was applied for comparison between two samples and one-way ANOVA was utilized for comparison between two groups. Results: The wound healing rate of PRP group was higher than that of control group on 3(rd,) 6(th,) 10(th) and 15(th) day (30.33±3.35 vs.18.35±2.04, 55.51±2.74 vs.36.83±2.34, 79.64±1.40 vs.56.92±1.44, 86.88±2.12 vs.65.80±1.76) after wound surface formation, there were statistic differences (t=13.66-50.48, all Pplasma may promote fibroblasts secreted collagen by activated and releasing all kinds of growth factors, especially type Ⅰ and type Ⅲ collagen to accelerate the wound healing.

  11. Synthesis and properties of collagen-g-poly(sodium acrylate-co-2-hydroxyethylacrylate superabsorbent hydrogels

    Directory of Open Access Journals (Sweden)

    M. Sadeghi

    2013-06-01

    Full Text Available Novel biopolymer-based superabsorbent hydrogels were prepared by grafting crosslinked poly(acrylic acid-co-2-hydroxyethyl acrylate (PAA-co-PHEA chains onto collagen backbones through a free radical polymerization method. The graft copolymerization reaction was carried out in a homogeneous medium and in the presence of ammonium persulfate (APS as initiator and N,N '-methylene bisacrylamide (MBA as crosslinker. A proposed mechanism for collagen-g-(PAA-co-PHEA formation was suggested and the hydrogel structure was confirmed using FTIR spectroscopy and TGA thermal analysis. Moreover, the morphology of the samples was examined by scanning electron microscopy (SEM. The effect of concentration of MBA as well as AA/HEA weight ratio on the swelling capacity of the hydrogel was also studied. Furthermore, the water absorbency of hydrogels was measured in solutions with pH ranging 1 to 13. The collagen-based hydrogel exhibited a pH-responsive character, so that a swelling-deswelling pulsatile behavior was recorded at pHs 2 and 8. Preliminary swelling and deswelling behaviors of the hydrogels were also studied. Additionally, the hydrogels exhibited salt-sensitivity and cation exchange properties.

  12. Synthesis, characterization and bioevaluation of drug-collagen hybrid materials for biomedical applications.

    Science.gov (United States)

    Voicu, Georgeta; Geanaliu-Nicolae, Ruxandra-Elena; Pîrvan, Adrian-Alexandru; Andronescu, Ecaterina; Iordache, Florin

    2016-08-30

    This work presents a study based on the preparation and characterization of drug-collagen hybrid materials. Materials used for obtaining drug-collagen hybrids were collagen type I (Coll) as matrix and fludarabine (F) and epirubicin (E) as hydrophilic active substances. After incorporation of drugs into Coll in different ratios, the obtained hybrid materials (Coll/F and Coll/E) could be used according to our results as potential drug delivery systems in medicine for the topical (local) treatment of cancerous tissues (e.g. the treatment of breast, stomach, lung, colorectal or advanced ovarian cancer). The materials were characterized considering their composition (by XRD, FT-IR and DTA-TG) and their morphology (by SEM). The delivery of drug was assessed by UV-vis. The in vitro citotoxicity demonstrates an antitumoral activity of the obtained hybrid materials and their potential use for biomedical applications as drug delivery systems in tumoral treatments. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Effects of processing on structural, mechanical and biological properties of collagen-based substrates for regenerative medicine.

    Science.gov (United States)

    Terzi, A; Storelli, E; Bettini, S; Sibillano, T; Altamura, D; Salvatore, L; Madaghiele, M; Romano, A; Siliqi, D; Ladisa, M; De Caro, L; Quattrini, A; Valli, L; Sannino, A; Giannini, C

    2018-01-23

    The aim of this work was to investigate the structural features of type I collagen isoforms and collagen-based films at atomic and molecular scales, in order to evaluate whether and to what extent different protocols of slurry synthesis may change the protein structure and the final properties of the developed scaffolds. Wide Angle X-ray Scattering data on raw materials demonstrated the preferential orientation of collagen molecules in equine tendon-derived collagens, while randomly oriented molecules were found in bovine skin collagens, together with a lower crystalline degree, analyzed by the assessment of FWHM (Full Width at Half Maximum), and a certain degree of salt contamination. WAXS and FT-IR (Fourier Transform Infrared) analyses on bovine collagen-based films, showed that mechanical homogenization of slurry in acidic solution was the treatment ensuring a high content of super-organization of collagen into triple helices and a high crystalline domain into the material. In vitro tests on rat Schwannoma cells showed that Schwann cell differentiation into myelinating cells was dependent on the specific collagen film being used, and was found to be stimulated in case of homogenization-treated samples. Finally DHT/EDC crosslinking treatment was shown to affect mechanical stiffness of films depending on collagen source and processing conditions.

  14. Delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells

    Directory of Open Access Journals (Sweden)

    Seung Eun Song

    2016-04-01

    Full Text Available This study examined the effect of delphinidin on high glucose-induced cell proliferation and collagen synthesis in mesangial cells. Glucose dose-dependently (5.6–25 mM increased cell proliferation and collagen I and IV mRNA levels, whereas pretreatment with delphinidin (50 μM prevented cell proliferation and the increased collagen mRNA levels induced by high glucose (25 mM. High glucose increased reactive oxygen species (ROS generation, and this was suppressed by pretreating delphinidin or the antioxidant N-acetyl cysteine. NADPH oxidase (NOX 1 was upregulated by high glucose, but pretreatment with delphinidin abrogated this upregulation. Increased mitochondrial superoxide by 25 mM glucose was also suppressed by delphinidin. The NOX inhibitor apocynin and mitochondria-targeted antioxidant Mito TEMPO inhibited ROS generation and cell proliferation induced by high glucose. Phosphorylation of extracellular signal regulated kinase (ERK1/2 was increased by high glucose, which was suppressed by delphinidin, apocynin or Mito TEMPO. Furthermore, PD98059 (an ERK1/2 inhibitor prevented the high glucose-induced cell proliferation and increased collagen mRNA levels. Transforming growth factor (TGF-β protein levels were elevated by high glucose, and pretreatment with delphinidin or PD98059 prevented this augmentation. These results suggest that delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells.

  15. Changes in content and synthesis of collagen types and proteoglycans in osteoarthritis of the knee joint and comparison of quantitative analysis with Photoshop-based image analysis.

    Science.gov (United States)

    Lahm, Andreas; Mrosek, Eike; Spank, Heiko; Erggelet, Christoph; Kasch, Richard; Esser, Jan; Merk, Harry

    2010-04-01

    The different cartilage layers vary in synthesis of proteoglycan and of the distinct types of collagen with the predominant collagen Type II with its associated collagens, e.g. types IX and XI, produced by normal chondrocytes. It was demonstrated that proteoglycan decreases in degenerative tissue and a switch from collagen type II to type I occurs. The aim of this study was to evaluate the correlation of real-time (RT)-PCR and Photoshop-based image analysis in detecting such lesions and find new aspects about their distribution. We performed immunohistochemistry and histology with cartilage tissue samples from 20 patients suffering from osteoarthritis compared with 20 healthy biopsies. Furthermore, we quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorimetrically. Using Adobe Photoshop the digitized images of histology and immunohistochemistry stains of collagen type I and II were stored on an external data storage device. The area occupied by any specific colour range can be specified and compared in a relative manner directly from the histogram using the "magic wand tool" in the select similar menu. In the image grow menu gray levels or luminosity (colour) of all pixels within the selected area, including mean, median and standard deviation, etc. are depicted. Statistical Analysis was performed using the t test. With the help of immunohistochemistry, RT-PCR and quantitative RT- PCR we found that not only collagen type II, but also collagen type I is synthesized by the cells of the diseased cartilage tissue, shown by increasing amounts of collagen type I mRNA especially in the later stages of osteoarthritis. A decrease of collagen type II is visible especially in the upper fibrillated area of the advanced osteoarthritic samples, which leads to an overall decrease. Analysis of proteoglycan showed a loss of the overall content and a quite uniform staining in

  16. Synthesis and characterization of hyaluronic acid/human-like collagen hydrogels

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jingjing; Ma, Xiaoxuan, E-mail: xiaoxuanma@163.com; Fan, Daidi, E-mail: fandaidi@nwu.edu.cn; Zhu, Chenhui; Deng, Jianjun; Hui, Junfeng; Ma, Pei

    2014-10-01

    Injectable hydrogel plays an important role in soft tissue filling and repair. We report an injectable hydrogel based on hyaluronic acid (HA) and human-like collagen (HLC), both with favorable biocompatibility and biodegradability. These two types of biomacromolecules were crosslinked with 1,4-butanediol diglycidyl ether to form a three-dimensional network. The redundant crosslinker was removed by dialysis and distillation. An HA-based hydrogel prepared by the same method was used as a control. The cytocompatibility was studied with a Cell Counting Kit-8 (CCK-8) test. Carbazole colorimetry was used to analyze the in vitro degradation rate. The histocompatibility was evaluated by hematoxylin and eosin (H and E) staining analysis and immunohistochemical analysis. The CCK-8 assay demonstrated that the HA/HLC hydrogel was less cytotoxic than the HA-based hydrogel and could promote baby hamster kidney cell (BHK) proliferation. The cell adhesion indicated that BHK could grow well on the surface of the materials and maintain good cell viability. The in vitro degradation test showed that the HA/HLC hydrogel had a longer degradation time and an excellent antienzyme ability. In vivo injection showed that there was little inflammatory response to HA/HLC after 1, 2, and 4 weeks. Therefore, the HA/HLC hydrogel is a promising biomaterial for soft tissue filling and repair. - Highlights: • Human-like collagen was used with hyaluronic acid to prepare soft tissue filling meterials. • 1,4-Butanediol diglycidyl ether (BDDE) was introduced to treat the hydrogels. • The addition of human-like collagen could improve the biological properties of hydrogels.

  17. Type I collagen synthesis and degradation in peritendinous tissue after exercise determined by microdialysis in humans

    DEFF Research Database (Denmark)

    Langberg, Henning; Skovgaard, D; Petersen, L J

    1999-01-01

    .e.m. values) for both radioactively labelled substances. 3. PICP concentration decreased in both interstitial peritendinous tissue and arterial blood immediately after exercise, but rose 3-fold from basal 72 h after exercise in the peritendinous tissue (55 +/- 10 microg l-1, mean +/- s.e.m. (rest) to 165...... as determined with microdialysis and using dialysate fibre with a very high molecular mass cut-off. This suggests an adaptation to acute physical loading also in non-bone-related collagen in humans....

  18. Flexor tendon tissue engineering: acellularization of human flexor tendons with preservation of biomechanical properties and biocompatibility.

    Science.gov (United States)

    Pridgen, Brian C; Woon, Colin Y L; Kim, Maxwell; Thorfinn, Johan; Lindsey, Derek; Pham, Hung; Chang, James

    2011-08-01

    Acellular human tendons are a candidate scaffold for tissue engineering flexor tendons of the hand. This study compared acellularization methods and their compatibility with allogeneic human cells. Human flexor tendons were pretreated with 0.1% ethylenediaminetetracetic acid (EDTA) for 4  h followed by 24  h treatments of 1% Triton X-100, 1% tri(n-butyl)phosphate, or 0.1% or 1% sodium dodecyl sulfate (SDS) in 0.1% EDTA. Outcomes were assessed histologically by hematoxylin and eosin and SYTO green fluorescent nucleic acid stains and biochemically by a QIAGEN DNeasy kit, Sircol collagen assay, and 1,9 dimethylmethylene blue glycosaminoglycan assay. Mechanical data were collected using a Materials Testing System to pull to failure tendons acellularized with 0.1% SDS. Acellularized tendons were re-seeded in a suspension of human dermal fibroblasts. Attachment of viable cells to acellularized tendon was assessed biochemically by a cell viability assay and histologically by a live/dead stain. Data are reported as mean±standard deviation. Compared with the DNA content of fresh tendons (551±212  ng DNA/mg tendon), only SDS treatments significantly decreased DNA content (1% SDS [202.8±37.4  ng DNA/mg dry weight tendon]; 0.1% SDS [189±104  ng DNA/mg tendon]). These findings were confirmed by histology. There was no decrease in glycosaminoglycans or collagen following acellularization with SDS. There was no difference in the ultimate tensile stress (55.3±19.2 [fresh] vs. 51.5±6.9 [0.1% SDS] MPa). Re-seeded tendons demonstrated attachment of viable cells to the tendon surface using a viability assay and histology. Human flexor tendons were acellularized with 0.1% SDS in 0.1% EDTA for 24  h with preservation of mechanical properties. Preservation of collagen and glycoaminoglycans and re-seeding with human cells suggest that this scaffold is biocompatible. This will provide a promising scaffold for future human flexor tendon tissue engineering studies to

  19. Sex differences in tendon structure and function.

    Science.gov (United States)

    Sarver, Dylan C; Kharaz, Yalda Ashraf; Sugg, Kristoffer B; Gumucio, Jonathan P; Comerford, Eithne; Mendias, Christopher L

    2017-10-01

    Tendons play a critical role in the transmission of forces between muscles and bones, and chronic tendon injuries and diseases are among the leading causes of musculoskeletal disability. Little is known about sex-based differences in tendon structure and function. Our objective was to evaluate the mechanical properties, biochemical composition, transcriptome, and cellular activity of plantarflexor tendons from 4 month old male and female C57BL/6 mice using in vitro biomechanics, mass spectrometry-based proteomics, genome-wide expression profiling, and cell culture techniques. While the Achilles tendons of male mice were approximately 6% larger than female mice (p differences in mechanical properties (p > 0.05) of plantaris tendons were observed. Mass spectrometry proteomics analysis revealed no significant difference between sexes in the abundance of major extracellular matrix (ECM) proteins such as collagen types I (p = 0.30) and III (p = 0.68), but female mice had approximately twofold elevations (p differed by only 1%. In vitro, neither the sex of the serum that fibroblasts were cultured in, nor the sex of the ECM in which they were embedded, had profound effects on the expression of collagen and cell proliferation genes. Our results indicate that while male mice expectedly had larger tendons, male and female tendons have very similar mechanical properties and biochemical composition, with small increases in some ECM proteins and proteoglycans evident in female tendons. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2117-2126, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  20. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist inhibits collagen synthesis in human hypertrophic scar fibroblasts by targeting Smad3 via miR-145

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hua-Yu; Li, Chao; Zheng, Zhao; Zhou, Qin; Guan, Hao; Su, Lin-Lin; Han, Jun-Tao; Zhu, Xiong-Xiang; Wang, Shu-yue; Li, Jun, E-mail: lijunfmmu@163.com; Hu, Da-Hai, E-mail: hudahaifmmu@aliyun.com

    2015-03-27

    The transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ) functions to regulate cell differentiation and lipid metabolism. Recently, its agonist has been documented to regulate extracellular matrix production in human dermal fibroblasts. This study explored the underlying molecular mechanisms and gene interactions in hypertrophic scar fibroblasts (HSFBs) in vitro. HSFBs were cultured and treated with or without PPAR-γ agonist or antagonist for gene expression. Bioinformatical analysis predicted that miR-145 could target Smad3 expression. Luciferase assay was used to confirm such an interaction. The data showed that PPAR-γ agonist troglitazone suppressed expression of Smad3 and Col1 in HSFBs. PPAR-γ agonist induced miR-145 at the gene transcriptional level, which in turn inhibited Smad3 expression and Col1 level in HSFBs. Furthermore, ELISA data showed that Col1 level in HSFBs was controlled by a feedback regulation mechanism involved in PPAR-γ agonist and antagonist-regulated expression of miR-145 and Smad3 in HSFBs. These findings indicate that PPAR-γ-miR-145-Smad3 axis plays a role in regulation of collagen synthesis in HSFBs. - Highlights: • PPAR-γ agonist inhibits collagen synthesis in HSFBs. • Smad3 and type I collagen expression are decreased by PPAR-γ agonist. • miR-145 expression is increased by PPAR-γ agonist in HSFBs. • Increased miR-145 inhibits collagen synthesis by targeting Smad3. • miR-145 regulates collagen synthesis.

  1. Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta

    Science.gov (United States)

    Cabral, Wayne A.; Ishikawa, Masaki; Garten, Matthias; Makareeva, Elena N.; Sargent, Brandi M.; Weis, MaryAnn; Barnes, Aileen M.; Webb, Emma A.; Shaw, Nicholas J.; Ala-Kokko, Leena; Lacbawan, Felicitas L.; Högler, Wolfgang; Leikin, Sergey; Blank, Paul S.; Zimmerberg, Joshua; Eyre, David R.; Yamada, Yoshihiko; Marini, Joan C.

    2016-01-01

    Recessive osteogenesis imperfecta (OI) is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50–70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes. PMID:27441836

  2. Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta.

    Directory of Open Access Journals (Sweden)

    Wayne A Cabral

    2016-07-01

    Full Text Available Recessive osteogenesis imperfecta (OI is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50-70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes.

  3. Synthesis of highly interconnected 3D scaffold from Arothron stellatus skin collagen for tissue engineering application.

    Science.gov (United States)

    Ramanathan, Giriprasath; Singaravelu, Sivakumar; Raja, M D; Sivagnanam, Uma Tiruchirapalli

    2015-11-01

    The substrate which is avidly used for tissue engineering applications should have good mechanical and biocompatible properties, and all these parameters are often considered as essential for dermal reformation. Highly interconnected three dimensional (3D) wound dressing material with enhanced structural integrity was synthesized from Arothron stellatus fish skin (AsFS) collagen for tissue engineering applications. The synthesized 3D collagen sponge (COL-SPG) was further characterized by different physicochemical methods. The scanning electron microscopy analysis of the material demonstrated that well interconnected pores with homogeneous microstructure on the surface aids higher swelling index and that the material also possessed good mechanical properties with a Young's modulus of 0.89±0.2 MPa. Biocompatibility of the 3D COL-SPG showed 92% growth for both NIH 3T3 fibroblasts and keratinocytes. Overall, the study revealed that synthesized 3D COL-SPG from fish skin will act as a promising wound dressing in skin tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Multi-Layer Electrospun Membrane Mimicking Tendon Sheath for Prevention of Tendon Adhesions

    Directory of Open Access Journals (Sweden)

    Shichao Jiang

    2015-03-01

    Full Text Available Defect of the tendon sheath after tendon injury is a main reason for tendon adhesions, but it is a daunting challenge for the biomimetic substitute of the tendon sheath after injury due to its multi-layer membrane-like structure and complex biologic functions. In this study, a multi-layer membrane with celecoxib-loaded poly(l-lactic acid-polyethylene glycol (PELA electrospun fibrous membrane as the outer layer, hyaluronic acid (HA gel as middle layer, and PELA electrospun fibrous membrane as the inner layer was designed. The anti-adhesion efficacy of this multi-layer membrane was compared with a single-layer use in rabbit flexor digitorum profundus tendon model. The surface morphology showed that both PELA fibers and celecoxib-loaded PELA fibers in multi-layer membrane were uniform in size, randomly arrayed, very porous, and smooth without beads. Multi-layer membrane group had fewer peritendinous adhesions and better gliding than the PELA membrane group and control group in gross and histological observation. The similar mechanical characteristic and collagen expression of tendon repair site in the three groups indicated that the multi-layer membrane did not impair tendon healing. Taken together, our results demonstrated that such a biomimetic multi-layer sheath could be used as a potential strategy in clinics for promoting tendon gliding and preventing adhesion without poor tendon healing.

  5. A fibre-reinforced poroviscoelastic model accurately describes the biomechanical behaviour of the rat Achilles tendon.

    Directory of Open Access Journals (Sweden)

    Hanifeh Khayyeri

    Full Text Available Computational models of Achilles tendons can help understanding how healthy tendons are affected by repetitive loading and how the different tissue constituents contribute to the tendon's biomechanical response. However, available models of Achilles tendon are limited in their description of the hierarchical multi-structural composition of the tissue. This study hypothesised that a poroviscoelastic fibre-reinforced model, previously successful in capturing cartilage biomechanical behaviour, can depict the biomechanical behaviour of the rat Achilles tendon found experimentally.We developed a new material model of the Achilles tendon, which considers the tendon's main constituents namely: water, proteoglycan matrix and collagen fibres. A hyperelastic formulation of the proteoglycan matrix enabled computations of large deformations of the tendon, and collagen fibres were modelled as viscoelastic. Specimen-specific finite element models were created of 9 rat Achilles tendons from an animal experiment and simulations were carried out following a repetitive tensile loading protocol. The material model parameters were calibrated against data from the rats by minimising the root mean squared error (RMS between experimental force data and model output.All specimen models were successfully fitted to experimental data with high accuracy (RMS 0.42-1.02. Additional simulations predicted more compliant and soft tendon behaviour at reduced strain-rates compared to higher strain-rates that produce a stiff and brittle tendon response. Stress-relaxation simulations exhibited strain-dependent stress-relaxation behaviour where larger strains produced slower relaxation rates compared to smaller strain levels. Our simulations showed that the collagen fibres in the Achilles tendon are the main load-bearing component during tensile loading, where the orientation of the collagen fibres plays an important role for the tendon's viscoelastic response. In conclusion, this

  6. A fibre-reinforced poroviscoelastic model accurately describes the biomechanical behaviour of the rat Achilles tendon.

    Science.gov (United States)

    Khayyeri, Hanifeh; Gustafsson, Anna; Heuijerjans, Ashley; Matikainen, Marko K; Julkunen, Petro; Eliasson, Pernilla; Aspenberg, Per; Isaksson, Hanna

    2015-01-01

    Computational models of Achilles tendons can help understanding how healthy tendons are affected by repetitive loading and how the different tissue constituents contribute to the tendon's biomechanical response. However, available models of Achilles tendon are limited in their description of the hierarchical multi-structural composition of the tissue. This study hypothesised that a poroviscoelastic fibre-reinforced model, previously successful in capturing cartilage biomechanical behaviour, can depict the biomechanical behaviour of the rat Achilles tendon found experimentally. We developed a new material model of the Achilles tendon, which considers the tendon's main constituents namely: water, proteoglycan matrix and collagen fibres. A hyperelastic formulation of the proteoglycan matrix enabled computations of large deformations of the tendon, and collagen fibres were modelled as viscoelastic. Specimen-specific finite element models were created of 9 rat Achilles tendons from an animal experiment and simulations were carried out following a repetitive tensile loading protocol. The material model parameters were calibrated against data from the rats by minimising the root mean squared error (RMS) between experimental force data and model output. All specimen models were successfully fitted to experimental data with high accuracy (RMS 0.42-1.02). Additional simulations predicted more compliant and soft tendon behaviour at reduced strain-rates compared to higher strain-rates that produce a stiff and brittle tendon response. Stress-relaxation simulations exhibited strain-dependent stress-relaxation behaviour where larger strains produced slower relaxation rates compared to smaller strain levels. Our simulations showed that the collagen fibres in the Achilles tendon are the main load-bearing component during tensile loading, where the orientation of the collagen fibres plays an important role for the tendon's viscoelastic response. In conclusion, this model can capture

  7. Lateral force transmission between human tendon fascicles

    DEFF Research Database (Denmark)

    Haraldsson, Bjarki T; Aagaard, Per; Qvortrup, Klaus

    2008-01-01

    Whether adjacent collagen fascicles transmit force in parallel is unknown. The purpose of the present study was to examine the magnitude of lateral force transmission between adjacent collagen fascicles from the human patellar and Achilles tendon. From each sample two adjacent strands of fascicles...... was transversally cut while the other fascicle and the fascicular membrane were kept intact. Cycle 3: both fascicles were cut in opposite ends while the fascicular membrane was left intact. A decline in peak force of 45% and 55% from cycle 1 to cycle 2, and 93% and 92% from cycle 2 to cycle 3 was observed...... in the patellar and Achilles tendon fascicles, respectively. A decline in stiffness of 39% and 60% from cycle 1 to cycle 2, and of 93% and 100% from cycle 2 to cycle 3 was observed in the patellar and Achilles tendon fascicles, respectively. The present data demonstrate that lateral force transmission between...

  8. The Effect of Sodium Hyaluronate on Ligamentation and Biomechanical Property of Tendon in Repair of Achilles Tendon Defect with Polyethylene Terephthalate Artificial Ligament: A Rabbit Tendon Repair Model.

    Science.gov (United States)

    Li, Shengkun; Ma, Kui; Li, Hong; Jiang, Jia; Chen, Shiyi

    2016-01-01

    The Achilles tendon is the most common ruptured tendon of human body. Reconstruction with polyethylene terephthalate (PET) artificial ligament is recommended in some serious cases. Sodium hyaluronate (HA) is beneficial for the healing of tendon injuries. We aimed to determine the effect of sodium hyaluronate in repair of Achilles tendon defect with PET artificial ligament in an animal tendon repair model. Sixteen New Zealand White rabbits were divided into two groups. Eight rabbits repaired with PET were assigned to PET group; the other eight rabbits repaired with PET along with injection of HE were assigned to HA-PET group. All rabbits were sacrificed at 4 and 8 weeks postoperatively for biomechanical and histological examination. The HA-PET group revealed higher biomechanical property compared with the PET group. Histologically, more collagen tissues grew into the HA-PET group compared with PET group. In conclusion, application of sodium hyaluronate can improve the healing of Achilles tendon reconstruction with polyethylene terephthalate artificial ligament.

  9. Poly-L-arginine based materials as instructive substrates for fibroblast synthesis of collagen.

    Science.gov (United States)

    Bygd, Hannah C; Akilbekova, Dana; Muñoz, Adam; Forsmark, Kiva D; Bratlie, Kaitlin M

    2015-09-01

    The interactions of cells and surrounding tissues with biomaterials used in tissue engineering, wound healing, and artificial organs ultimately determine their fate in vivo. We have demonstrated the ability to tune fibroblast responses with the use of varied material chemistries. In particular, we examined cell morphology, cytokine production, and collagen fiber deposition angles in response to a library of arginine-based polymeric materials. The data presented here shows a large range of vascular endothelial growth factor (VEGF) secretion (0.637 ng/10(6) cells/day to 3.25 ng/10(6) cells/day), cell migration (∼15 min materials in wound healing and tissue engineering applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Achilles Tendon Rupture

    Science.gov (United States)

    ... Achilles tendon rupture. Obesity. Excess weight puts more strain on the tendon. Prevention To reduce your chance of developing Achilles tendon problems, follow these tips: Stretch and strengthen calf muscles. Stretch your calf until you feel a noticeable ...

  11. Posterior Tibial Tendon Dysfunction

    Science.gov (United States)

    .org Posterior Tibial Tendon Dysfunction Page ( 1 ) Posterior tibial tendon dysfunction is one of the most common problems of the foot and ankle. It occurs when the posterior tibial tendon becomes inflamed or torn. As a result, the ...

  12. Achilles tendon repair

    Science.gov (United States)

    Achilles tendon rupture-surgery; Percutaneous Achilles tendon rupture repair ... To fix your torn Achilles tendon, the surgeon will: Make a cut down the back of your heel Make several small cuts rather than one large ...

  13. Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern

    DEFF Research Database (Denmark)

    Eliasson, Pernilla; Svensson, Rene B; Giannopoulos, Antonis

    2017-01-01

    investigated the effect of statin treatment on mechanical strength, cell proliferation, collagen content and gene expression pattern in a tendon-like tissue made from human tenocytes in vitro. Human tendon fibroblasts were grown in a 3D tissue culture model (tendon constructs), and treated with either...... expression pattern and a reduced collagen content indicated a disturbed balance in matrix production of tendon due to statin administration....

  14. Contraction intensity and feeding affect collagen and myofibrillar protein synthesis rates differently in human skeletal muscle

    DEFF Research Database (Denmark)

    Holm, Lars; van Hall, Gerrit; Rose, Adam

    2010-01-01

    with the fasting condition. The Rp-s6k-4E-binding protein-1 (BP1) and the mitogen-activated protein kinase (MAPk) pathways were activated by the HL intensity and were suggested to be responsible for regulating myofibrillar FSR in response to adequate contractile activity. Feeding predominantly affected Rp-s6k...... to contractile activity, whereas elongation mainly was found to respond to feeding. Furthermore, although functionally linked, the contractile and the supportive matrix structures upregulate their protein synthesis rate quite differently in response to feeding and contractile activity and intensity.......Exercise stimulates muscle protein fractional synthesis rate (FSR), but the importance of contractile intensity and whether it interplays with feeding is not understood. This was investigated following two distinct resistance exercise (RE) contraction intensities using an intrasubject design...

  15. Synthesis and characterization of biocomposites with different hydroxyapatite-collagen ratios.

    Science.gov (United States)

    Sena, Lidia A; Caraballo, Mirta M; Rossi, Alexandre M; Soares, Gloria A

    2009-12-01

    Hydroxyapatite (HA)-type I collagen (Col) composite is a tissue-engineered bone graft which can act as a carrier or a template structure for cells or any other agents. In this paper, the effect of Col ratio on the scaffold structure and composition was analyzed. Scaffolds composed by HA/Col with different weight ratios (80:20; 50:50; 20:80, and 10:90) were produced by the precipitation method at pH 8-9, 37 degrees C and 6 h of ripening. Using X-ray diffraction data, the Rietveld structure refinement showed that the size of HA crystals along the c-axis direction (002) decreases significantly in the presence of Col. Thus, the HA crystal shape turned from needle-like in pure HA, into spherical, in the 10:90 composite due to Col fibrillogenesis. The homogeneity of the composite was significantly dependent on the amount of Col in it. HA/Col 20/80 composite presented HA particles in a more homogenous way. Such a biocomposite was successfully produced in a rapid way and it is potentially useful for both small tissue repairs and engineering.

  16. Synthesis and characterization of ibandronate-loaded silica nanoparticles and collagen nanocomposites.

    Science.gov (United States)

    Alvarez, Gisela S; Echazu, Maria I Alvarez; Olivetti, Christian E; Desimone, Martin F

    2015-01-01

    Non-porous bare silica nanoparticles, amine modified silica nanoparticles and mesoporous particles, were evaluated as carriers for sodium ibandronate. The synthesized nanoparticles were characterized by SEM, TEM, DLS and porosity. Then, their capacity to incorporate a bisphosphonate drug (sodium ibandronate) and the in vitro release behavior was analyzed by capillary electrophoresis. Mesoporous and amine-modified particles showed higher levels of drug incorporation, 44.68 mg g(-1) and 28.90 mg g(-1), respectively. The release kinetics from the two types of particles was similar following a first order kinetics. However, when these particles were included into collagen hydrogels only mesoporous nanoparticles had a sustained release for over 10 days. The biocompatibility of mesoporous particles towards Saos-2 cells was also evaluated by the MTT assay observing an increase in cell viability for concentrations lower than 0.6 mg ml(-1) of particles and a decrease for concentrations over 1.2 mg ml(-1). Furthermore, when these particles were incubated with mesenchymal cells it was observed that they had the capacity to promote the differentiation of the cells with a significant increase in the alkaline phosphatase activity.

  17. Collagen breakdown products and lung collagen metabolism: an in vitro study on fibroblast cultures.

    OpenAIRE

    Gardi, C.; Calzoni, P; Marcolongo, P.; Cavarra, E.; Vanni, L.; Lungarella, G

    1994-01-01

    BACKGROUND--In fibrotic diseases such as pulmonary fibrosis there is evidence suggesting enhanced synthesis and degradation of lung connective tissue components, including collagen. It has therefore been hypothesised that products of collagen degradation may have a role in the promotion of collagen deposition. In support of this hypothesis, it has recently been shown that intravenous injection of lung collagen degradation products in experimental animals stimulated collagen synthesis leading ...

  18. The dermatan sulfate proteoglycan decorin modulates α2β1 integrin and the vimentin intermediate filament system during collagen synthesis.

    Directory of Open Access Journals (Sweden)

    Oliver Jungmann

    Full Text Available Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(-/- mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(-/- mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(-/- fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, we identified vimentin as one of the proteins that was differentially upregulated by the presence of decorin. We discovered that a decorin-deficient matrix leads to abnormal nuclear morphology in the Dcn(-/- fibroblasts. This phenotype could be rescued by the decorin proteoglycan but less efficiently by the decorin protein core. Decorin treatment led to a significant reduction of the α2β1 integrin at day 6 in Dcn(-/- fibroblasts, whereas the protein core had no effect on β1. Interestingly, only the decorin core induced mRNA synthesis, phosphorylation and de novo synthesis of vimentin indicating that the proteoglycan decorin in the extracellular matrix stabilizes the vimentin intermediate filament system. We could support these results in vivo, because the dermis of wild-type mice have more vimentin and less β1 integrin compared to Dcn(-/-. Furthermore, the α2β1 null fibroblasts also showed a reduced amount of vimentin compared to wild-type. These data show for the first time that decorin has an impact on the biology of α2β1 integrin and the vimentin intermediate filament system. Moreover, our findings provide a mechanistic explanation for the reported defects in wound healing associated with the Dcn(-/- phenotype.

  19. [Animal experiment study of healing of the sutured flexor tendon].

    Science.gov (United States)

    Martini, A K; Blimke, B

    1992-01-01

    The purpose of the present study was to determine whether tendons contain intrinsic cells capable of repair. To accomplish this, rabbit flexor tendons were exposed microsurgically, cut through, resutured and transferred as free transplant into the knee-joint. Immobilisation of the knee-joint will cause progressive formation of adhesions permitting neovascularisation of the transplant. Both is not observed when sutured flexor tendons were put in a knee articulation with full range of joint motion. Transmission electron micrography revealed up to 8 weeks after implantation vital cells and incidences of collagen neosynthesis independently whether adhesions existed or not. Histologically intrinsic repair was confirmed in mobile transplants and mainly initiated by cells of the visceral synovial sheet which form an anatomic-surgical unity with the tendon. In conclusion the importance of the synovial fluid for the tendon nutrition is underlined by the fact that an intrinsic healing of flexor tendon is possible without formation of adhesions.

  20. Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas.

    Science.gov (United States)

    Kabza, Michal; Karolak, Justyna A; Rydzanicz, Malgorzata; Szcześniak, Michał W; Nowak, Dorota M; Ginter-Matuszewska, Barbara; Polakowski, Piotr; Ploski, Rafal; Szaflik, Jacek P; Gajecka, Marzena

    2017-05-01

    To understand better the factors contributing to keratoconus (KTCN), we performed comprehensive transcriptome profiling of human KTCN corneas for the first time using an RNA-Seq approach. Twenty-five KTCN and 25 non-KTCN corneas were enrolled in this study. After RNA extraction, total RNA libraries were prepared and sequenced. The discovery RNA-Seq analysis (in eight KTCN and eight non-KTCN corneas) was conducted first, after which the replication RNA-Seq experiment was performed on a second set of samples (17 KTCN and 17 non-KTCN corneas). Over 82% of the genes and almost 75% of the transcripts detected as differentially expressed in KTCN and non-KTCN corneas were confirmed in the replication study using another set of samples. We used these differentially expressed genes to generate a network of KTCN-deregulated genes. We found an extensive disruption of collagen synthesis and maturation pathways, as well as downregulation of the core elements of the TGF-β, Hippo, and Wnt signaling pathways influencing corneal organization. This first comprehensive transcriptome profiling of human KTCN corneas points further to a complex etiology of KTCN.

  1. Chemical and biotechnological processing of collagen-containing raw materials into functional components of feed suitable for production of high-quality meat from farm animals

    Science.gov (United States)

    Baburina, M. I.; Ivankin, A. N.; Stanovova, I. A.

    2017-09-01

    The process of chemical biotechnological processing of collagen-containing raw materials into functional components of feeds for effective pig rearing was studied. Protein components of feeds were obtained as a result of hydrolysis in the presence of lactic acid of the animal collagen from secondary raw materials, which comprised subcutaneous collagen (cuticle), skin and veined mass with tendons from cattle. For comparison, a method is described for preparing protein components of feeds by cultivating Lactobacillus plantarum. Analysis of the kinetic data of the conversion of a high-molecular collagen protein to an aminolyte polypeptide mixture showed the advantage of microbiological synthesis in obtaining a protein for feeds. Feed formulations have been developed to include the components obtained, and which result in high quality pork suitable for the production of quality meat products.

  2. Collagen telopeptides (cross-linking sites) play a role in collagen gel lattice contraction

    Science.gov (United States)

    Woodley, D. T.; Yamauchi, M.; Wynn, K. C.; Mechanic, G.; Briggaman, R. A.

    1991-01-01

    Solubilized interstitial collagens will form a fibrillar, gel-like lattice when brought to physiologic conditions. In the presence of human dermal fibroblasts the collagen lattice will contract. The rate of contraction can be determined by computer-assisted planemetry. The mechanisms involved in contraction are as yet unknown. Using this system it was found that the rate of contraction was markedly decreased when collagen lacking telopeptides was substituted for native collagen. Histidinohydroxylysinonorleucine (HHL) is a major stable trifunctional collagen cross-link in mature skin that involves a carboxyl terminal, telopeptide site 16c, the sixteenth amino acid residue from the carboxy terminal of the telopeptide region of alpha 1 (I) in type I collagen. Little, if any, HHL was present in native, purified, reconstituted, soluble collagen fibrils from 1% acetic acid-extracted 2-year-old bovine skin. In contrast, HHL cross-links were present (0.22 moles of cross-link per mole of collagen) in lattices of the same collagen contracted by fibroblasts. However, rat tail tendon does not contain HHL cross-links, and collagen lattices made of rat tail tendon collagen are capable of contraction. This suggests that telopeptide sites, and not mature HHL cross-links per se, are essential for fibroblasts to contract collagen lattices. Beta-aminopropionitrile fumarate (BAPN), a potent lathyrogen that perturbs collagen cross-linking by inhibition of lysyl oxidase, also inhibited the rate of lattice cell contraction in lattices composed of native collagen. However, the concentrations of BAPN that were necessary to inhibit the contraction of collagen lattices also inhibited fibroblast growth suggestive of cellular toxicity. In accordance with other studies, we found no inhibition of the rate of lattice contraction when fibronectin-depleted serum was used. Electron microscopy of contracted gels revealed typical collagen fibers with a characteristic axial periodicity. The data

  3. Flexor tendon nutrition.

    Science.gov (United States)

    Manske, P R; Lesker, P A

    1985-02-01

    The concepts regarding nutrient pathways to flexor tendons within the digital sheath are reviewed. Historically, both diffusion and perfusion have been considered significant pathways to the flexor tendon. Theories of tendon healing and adhesion formation, as well as techniques employed by the surgeon in the repair of tendons, are based on these concepts.

  4. Low-Level Light Therapy with 410 nm Light Emitting Diode Suppresses Collagen Synthesis in Human Keloid Fibroblasts: An In Vitro Study

    Science.gov (United States)

    Lee, Hyun Soo; Jung, Soo-Eun; Kim, Sue Kyung; Kim, You-Sun; Sohn, Seonghyang

    2017-01-01

    Background Keloids are characterized by excessive collagen deposition in the dermis, in which transforming growth factor β (TGF-β)/Smad signaling plays an important role. Low-level light therapy (LLLT) is reported as effective in preventing keloids in clinical reports, recently. To date, studies investigating the effect of LLLT on keloid fibroblasts are extremely rare. Objective We investigated the effect of LLLT with blue (410 nm), red (630 nm), and infrared (830 nm) light on the collagen synthesis in keloid fibroblasts. Methods Keloid fibroblasts were isolated from keloid-revision surgery samples and irradiated using 410-, 630-, 830-nm light emitting diode twice, with a 24-hour interval at 10 J/cm2. After irradiation, cells were incubated for 24 and 48 hours and real-time quantitative reverse transcription polymerase chain reaction was performed. Western blot analysis was also performed in 48 hours after last irradiation. The genes and proteins of collagen type I, TGF-β1, Smad3, and Smad7 were analyzed. Results We observed no statistically significant change in the viability of keloid fibroblasts after irradiation. Collagen type I was the only gene whose expression significantly decreased after irradiation at 410 nm when compared to the non-irradiated control. Western blot analysis showed that LLLT at 410 nm lowered the protein levels of collagen type I compared to the control. Conclusion LLLT at 410 nm decreased the expression of collagen type I in keloid fibroblasts and might be effective in preventing keloid formation in their initial stage. PMID:28392641

  5. IL-13 promotes collagen accumulation in Crohn's disease fibrosis by down-regulation of fibroblast MMP synthesis: a role for innate lymphoid cells?

    Directory of Open Access Journals (Sweden)

    Jennifer R Bailey

    Full Text Available BACKGROUND: Fibrosis is a serious consequence of Crohn's disease (CD, often necessitating surgical resection. We examined the hypothesis that IL-13 may promote collagen accumulation within the CD muscle microenvironment. METHODS: Factors potentially modulating collagen deposition were examined in intestinal tissue samples from fibrotic (f CD and compared with cancer control (C, ulcerative colitis (UC and uninvolved (u CD. Mechanisms attributable to IL-13 were analysed using cell lines derived from uninvolved muscle tissue and tissue explants. RESULTS: In fCD muscle extracts, collagen synthesis was significantly increased compared to other groups, but MMP-2 was not co-ordinately increased. IL-13 transcripts were highest in fCD muscle compared to muscle from other groups. IL-13 receptor (R α1 was expressed by intestinal muscle smooth muscle, nerve and KIR(+ cells. Fibroblasts from intestinal muscle expressed Rα1, phosphorylated STAT6 in response to IL-13, and subsequently down-regulated MMP-2 and TNF-α-induced MMP-1 and MMP-9 synthesis. Cells with the phenotype KIR(+CD45(+CD56(+/-CD3(- were significantly increased in fCD muscle compared to all other groups, expressed Rα1 and membrane IL-13, and transcribed high levels of IL-13. In explanted CD muscle, these cells did not phosphorylate STAT6 in response to exogenous IL-13. CONCLUSIONS: The data indicate that in fibrotic intestinal muscle of Crohn's patients, the IL-13 pathway is stimulated, involving a novel population of infiltrating IL-13Rα1(+, KIR(+ innate lymphoid cells, producing IL-13 which inhibits fibroblast MMP synthesis. Consequently, matrix degradation is down-regulated and this leads to excessive collagen deposition.

  6. Iliopsoas Tendon Reformation after Psoas Tendon Release

    Directory of Open Access Journals (Sweden)

    K. Garala

    2013-01-01

    Full Text Available Internal snapping hip syndrome, or psoas tendonitis, is a recognised cause of nonarthritic hip pain. The majority of patients are treated conservatively; however, occasionally patients require surgical intervention. The two surgical options for iliopsoas tendinopathy are step lengthening of the iliopsoas tendon or releasing the tendon at the lesser trochanter. Although unusual, refractory snapping usually occurs soon after tenotomy. We report a case of a 47-year-old active female with internal snapping and pain following an open psoas tenotomy. Postoperatively she was symptom free for 13 years. An MRI arthrogram revealed reformation of a pseudo iliopsoas tendon reinserting into the lesser trochanter. The pain and snapping resolved after repeat iliopsoas tendon release. Reformation of tendons is an uncommon sequela of tenotomies. However the lack of long-term studies makes it difficult to calculate prevalence rates. Tendon reformation should be included in the differential diagnosis of failed tenotomy procedures after a period of symptom relief.

  7. Collagenous Gastritis

    OpenAIRE

    Freeman, Hugh J.; Piercy, James R.A.; Raine, Robert J.

    1989-01-01

    A 54-year-old woman presented with nausea, vomiting and weight loss associated with impaired gastric emptying necessitating institution of parenteral nutrition. Subsequent studies revealed an unusual gastric mucosa! inflammatory process characterized by unique subepithelial collagenous deposits. Collagenous gastritis appears to be a distinct, possibly immune-mediated, chronic disorder, pathologically reminiscent of collagenous sprue and collagenous colitis.

  8. Peroneal tendon disorders

    OpenAIRE

    Davda, Kinner; Malhotra, Karan; O'Donnell, Paul; Singh, Dishan; Cullen, Nicholas

    2017-01-01

    Pathological abnormality of the peroneal tendons is an under-appreciated source of lateral hindfoot pain and dysfunction that can be difficult to distinguish from lateral ankle ligament injuries. Enclosed within the lateral compartment of the leg, the peroneal tendons are the primary evertors of the foot and function as lateral ankle stabilisers. Pathology of the tendons falls into three broad categories: tendinitis and tenosynovitis, tendon subluxation and dislocation, and tendon splits and ...

  9. Endoscopic adhesiolysis for extensive tibialis posterior tendon and Achilles tendon adhesions following compound tendon rupture

    OpenAIRE

    Lui, Tun Hing

    2013-01-01

    Tendon adhesion is one of the most common causes of disability following tendon surgery. A case of extensive peritendinous adhesions of the Achilles tendon and tibialis posterior tendon after compound rupture of the tendons was reported. This was managed by endoscopic adhesiolysis of both tendons. The endoscopic approach allows early postoperative mobilisation which can relieve the tendon adhesion.

  10. Fibrocartilage associated with human tendons and their pulleys.

    Science.gov (United States)

    Benjamin, M; Qin, S; Ralphs, J R

    1995-12-01

    The presence of fibrocartilage in tendons that wrap around bony or fibrous pulleys is well known. It is an adaptation to resisting compression or shear, but the extent to which the structure of most human tendons is modified where they contact pulleys is less clear, for there has been no single comprehensive survey of a large number of sites. Less is known of the structure of the corresponding pulleys. In the present study, 38 regions of tendons that wrap around bony pulleys or pass beneath fibrous retinacula have been studied in routine histology sections taken from each of 2 or 3 elderly dissecting room cadavers. Most of the corresponding pulleys have also been examined. Fibrocartilage was present in 22 of the 38 tendon sites and it was most conspicuous where the tendons pressed predominantly against bone rather than retinacula and where they showed a large change in direction. Fibrocartilage was more characteristic of tendons at the ankle than the wrist, probably because the long axis of the foot is at right angles to that of the leg. There was considerable variation in the structure of tendon fibrocartilage. The most fibrocartilaginous tendons had oval or round cells embedded in a highly metachromatic matrix with interwoven or spiralling collagen fibres. At other sites, fibrocartilage cells were arranged in rows between parallel collagen fibres. The differences probably relate to differences in development. A single tendon could be modified at successive points along its length and fibrocartilage could be present in the endotenon and epitenon as well as in the tendon itself. Pathological changes seen in 'wrap around' tendons were fragmentation and partial delamination of the compressed surface, chondrocyte clustering, fatty infiltration and bone formation. Three types of pulleys were described for tendons--bony prominences and grooves, fibrous retinacula and synovial joints. The extent of cartilaginous differentiation on the periosteum of bony pulleys

  11. Low transformation growth factor-β1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Andreia Ferreira Barros

    2014-04-01

    Full Text Available Undernourished mice infected (UI submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers’ fibrosis in humans. In this report, the effects of the host’s nutritional status on parasite (worm load, egg viability and maturation and host (growth curves, biology, collagen synthesis and characteristics of the immunological response were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF-β1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-β1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

  12. Low-cost processing technology for the synthesis of calcium phosphates/collagen biocomposites for potential bone tissue engineering applications

    Directory of Open Access Journals (Sweden)

    Maria Helena Santos

    2007-12-01

    Full Text Available In the present study two novel composites of Calcium phosphates (CaP and Collagen (COL were synthesized, hydroxyapatite/Collagen (HA/COL and hydroxyapatite-btricalcium phosphate/COL (HAbTCP/COL. Collagen was extracted from bovine pericardium submitted to enzymatic digestion and purification by ion-exchange chromatography yielding high purity grade type I collagen. Biocomposites of HAP/COL and HAbTCP/COL were produced with a calcium phosphate/COL ratio of 80/20 (wt. (% and were characterized by chemical analysis, light microscopy and scanning electron microscopy, X ray diffraction and FT-infrared spectroscopy. SEM results of the CaP powders showed agglomerates of particles at the nanometric size range with predominantly columnar shape and average chemical composition of [Ca/P] = 1.67. FTIR analysis of collagen has confirmed the major vibrational bands associated with chemical groups like amides and hydroxyls usually found in proteins. SEM micrographs have indicated that both morphological and structural features and chemical composition of the composites were very similar to their precursors, collagen and calcium phosphate components. SDS-PAGE characterization results of protein extracted and purified has showed that bovine type I collagen was successfully obtained. Finally, the biocomposites presented a homogeneous aspect with the calcium phosphate particles aggregated to the collagen fibers. Hence, the novel developed biocomposites have high potential to be used for rebuilding small lesions in bone tissue engineering.

  13. The development of zebrafish tendon and ligament progenitors

    Science.gov (United States)

    Chen, Jessica W.; Galloway, Jenna L.

    2014-01-01

    Despite the importance of tendons and ligaments for transmitting movement and providing stability to the musculoskeletal system, their development is considerably less well understood than that of the tissues they serve to connect. Zebrafish have been widely used to address questions in muscle and skeletal development, yet few studies describe their tendon and ligament tissues. We have analyzed in zebrafish the expression of several genes known to be enriched in mammalian tendons and ligaments, including scleraxis (scx), collagen 1a2 (col1a2) and tenomodulin (tnmd), or in the tendon-like myosepta of the zebrafish (xirp2a). Co-expression studies with muscle and cartilage markers demonstrate the presence of scxa, col1a2 and tnmd at sites between the developing muscle and cartilage, and xirp2a at the myotendinous junctions. We determined that the zebrafish craniofacial tendon and ligament progenitors are neural crest derived, as in mammals. Cranial and fin tendon progenitors can be induced in the absence of differentiated muscle or cartilage, although neighboring muscle and cartilage are required for tendon cell maintenance and organization, respectively. By contrast, myoseptal scxa expression requires muscle for its initiation. Together, these data suggest a conserved role for muscle in tendon development. Based on the similarities in gene expression, morphology, collagen ultrastructural arrangement and developmental regulation with that of mammalian tendons, we conclude that the zebrafish tendon populations are homologous to their force-transmitting counterparts in higher vertebrates. Within this context, the zebrafish model can be used to provide new avenues for studying tendon biology in a vertebrate genetic system. PMID:24803652

  14. Expression, content, and localization of insulin-like growth factor I in human achilles tendon

    DEFF Research Database (Denmark)

    Olesen, Jens L; Heinemeier, Katja M; Langberg, Henning

    2006-01-01

    In animals insulin-like growth factor I (IGF-I) stimulates collagen production by fibroblasts and is expressed in tendons together with its binding protein 4 (IGFBP-4). However, the presence of IGF-I and IGFBP-4 in human tendon tissue is not described. Tissue IGF-I content was examined by immunof...... the tendon fibroblasts and that mRNA for IGF-I and IGFBP-4 can be determined in human tendon tissue. The present study adds support for the roles of IGF-I and IGFBP-4 in the regulation of tendon adaptive responses to mechanical loading....

  15. On the synthesis and characterization of β-tricalcium phosphate scaffolds coated with collagen or poly (D, L-lactic acid) for alveolar bone augmentation.

    Science.gov (United States)

    Deschamps, Isadora S; Magrin, Gabriel L; Magini, Ricardo S; Fredel, Márcio C; Benfatti, Cesar A M; M Souza, Júlio C

    2017-01-01

    After tooth loss, dimensional alterations on the alveolar bone ridge can occur that can negatively affect the placement of dental implants. The purpose of this study was to evaluate the synthesis, and mechanical properties of β-tricalcium phosphate (β-TCP) scaffolds coated with bioabsorbable polymers, namely, collagen and poly (D, L-lactic acid) (PDLLA). β-TCP powder was obtained by reactive milling and then characterized by X-ray diffraction and scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS). β-TCP scaffolds were obtained by replica method, in which polyurethane foams are immersed in β-TCP suspension and thereafter submitted to a thermal treatment to remove the polyurethane and sinter the ceramic. Type-I collagen or PDLLA were used to coat the β-TCP scaffolds by dip-coating method. Scaffolds were separated in four groups depending on the coating material: noncoated (Group A), double immersion in collagen (Group B), double immersion in PDLLA (Group C), and ten immersions in PDLLA (Group D). Samples were characterized by compressive tests and SEM/EDS. Data were statistically analyzed through two-way ANOVA (p = 0.05). Chemical and microscopic analyses revealed proper morphology and chemical composition of powder particles and scaffolds with or without polymeric coatings. Scaffolds coated with PDLLA showed higher compressive strength (0.11 ± 0.054 MPa) than those of collagen (0.022 ± 0.012 MPa) or noncoated groups (0.024 ± 0.012 MPa). The coating method of β-TCP with PDLLA revealed a potential strategy to increase the mechanical strength of porous ceramic materials while collagen can enhance cell migration.

  16. Greener synthesis of electrospun collagen/hydroxyapatite composite fibers with an excellent microstructure for bone tissue engineering

    Science.gov (United States)

    Zhou, Yuanyuan; Yao, Hongchang; Wang, Jianshe; Wang, Dalu; Liu, Qian; Li, Zhongjun

    2015-01-01

    In bone tissue engineering, collagen/hydroxyapatite (HAP) fibrous composite obtained via electrospinning method has been demonstrated to support the cells’ adhesion and bone regeneration. However, electrospinning of natural collagen often requires the use of cytotoxic organic solvents, and the HAP crystals were usually aggregated and randomly distributed within a fibrous matrix of collagen, limiting their clinical potential. Here, an effective and greener method for the preparation of collagen/HAP composite fibers was developed for the first time, and this green product not only had 40 times higher mechanical properties than that previously reported, but also had an excellent microstructure similar to that of natural bone. By dissolving type I collagen in environmentally friendly phosphate buffered saline/ethanol solution instead of the frequently-used cytotoxic organic solvents, followed with the key step of desalination, co-electrospinning the collagen solution with the HAP sol, generates a collagen/HAP composite with a uniform and continuous fibrous morphology. Interestingly, the nano-HAP needles were found to preferentially orient along the longitudinal direction of the collagen fibers, which mimicked the nanostructure of natural bones. Based on the characterization of the related products, the formation mechanism for this novel phenomenon was proposed. After cross-linking with 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride/N-hydroxysuccinimide, the obtained composite exhibited a significant enhancement in mechanical properties. In addition, the biocompatibility of the obtained composite fibers was evaluated by in vitro culture of the human myeloma cells (U2-OS). Taken together, the process outlined herein provides an effective, non-toxic approach for the fabrication of collagen/HAP composite nanofibers that could be good candidates for bone tissue engineering. PMID:25995630

  17. Collagen turnover after tibial fractures

    DEFF Research Database (Denmark)

    Joerring, S; Krogsgaard, M; Wilbek, H

    1994-01-01

    Collagen turnover after tibial fractures was examined in 16 patients with fracture of the tibial diaphysis and in 8 patients with fracture in the tibial condyle area by measuring sequential changes in serological markers of turnover of types I and III collagen for up to 26 weeks after fracture....... The markers were the carboxy-terminal extension peptide of type I procollagen (PICP), the amino-terminal extension peptide of type III procollagen (PIIINP), and the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP). The latter is a new serum marker of degradation of type I...... collagen. A group comparison showed characteristic sequential changes in the turnover of types I and III collagen in fractures of the tibial diaphysis and tibial condyles. The turnover of type III collagen reached a maximum after 2 weeks in both groups. The synthesis of type I collagen reached a maximum...

  18. Diseases of the tendons and tendon sheaths.

    Science.gov (United States)

    Steiner, Adrian; Anderson, David E; Desrochers, André

    2014-03-01

    Contracted flexor tendon leading to flexural deformity is a common congenital defect in cattle. Arthrogryposis is a congenital syndrome of persistent joint contracture that occurs frequently in Europe as a consequence of Schmallenberg virus infection of the dam. Spastic paresis has a hereditary component, and affected cattle should not be used for breeding purposes. The most common tendon avulsion involves the deep digital flexor tendon. Tendon disruptions may be successfully managed by tenorrhaphy and external coaptation or by external coaptation alone. Medical management alone is unlikely to be effective for purulent tenosynovitis. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Mineral distributions at the developing tendon enthesis.

    Directory of Open Access Journals (Sweden)

    Andrea G Schwartz

    Full Text Available Tendon attaches to bone across a functionally graded interface, "the enthesis". A gradient of mineral content is believed to play an important role for dissipation of stress concentrations at mature fibrocartilaginous interfaces. Surgical repair of injured tendon to bone often fails, suggesting that the enthesis does not regenerate in a healing setting. Understanding the development and the micro/nano-meter structure of this unique interface may provide novel insights for the improvement of repair strategies. This study monitored the development of transitional tissue at the murine supraspinatus tendon enthesis, which begins postnatally and is completed by postnatal day 28. The micrometer-scale distribution of mineral across the developing enthesis was studied by X-ray micro-computed tomography and Raman microprobe spectroscopy. Analyzed regions were identified and further studied by histomorphometry. The nanometer-scale distribution of mineral and collagen fibrils at the developing interface was studied using transmission electron microscopy (TEM. A zone (∼20 µm exhibiting a gradient in mineral relative to collagen was detected at the leading edge of the hard-soft tissue interface as early as postnatal day 7. Nanocharacterization by TEM suggested that this mineral gradient arose from intrinsic surface roughness on the scale of tens of nanometers at the mineralized front. Microcomputed tomography measurements indicated increases in bone mineral density with time. Raman spectroscopy measurements revealed that the mineral-to-collagen ratio on the mineralized side of the interface was constant throughout postnatal development. An increase in the carbonate concentration of the apatite mineral phase over time suggested possible matrix remodeling during postnatal development. Comparison of Raman-based observations of localized mineral content with histomorphological features indicated that development of the graded mineralized interface is linked

  20. A pharmaceutical preparation of Salvia miltiorrhiza protects cardiac myocytes from tumor necrosis factor-induced apoptosis and reduces angiotensin II-stimulated collagen synthesis in fibroblasts.

    Science.gov (United States)

    Ling, Shanhong; Luo, Ruizhi; Dai, Aozhi; Guo, Zhixin; Guo, Ruoling; Komesaroff, Paul A

    2009-01-01

    Salvia miltiorrhiza is a medicinal herb commonly used in traditional Chinese medicine for the prevention and treatment of cardiovascular disease. This study investigated the effects of Cardiotonic Pill (CP), a pharmaceutical preparation of Salvia miltiorrhiza, on cardiac myocytes and fibroblasts with respect to the viability, proliferation, and collagen synthesis in these cells under various conditions. A cardiac myocyte line, H9c2, and primarily cultured fibroblasts from rat hearts were incubated with CP over a broad concentration range (50-800 microg/ml) under normal cultures, conditions of ischemia (serum-free culture), and stimulation by angiotensin II (AII, 100 nM), hydrogen peroxide (H(2)O(2), 50-200 microM), or tumor necrosis factor alpha (TNFalpha, 40 ng/ml) for 24-48 h. Cell growth, apoptosis, DNA and collagen synthesis, and expression of relevant genes were assessed via cell number study, morphological examination, Annexin-V staining, flow-cytometry, [(3)H]-thymidine or [(3)H]-proline incorporation assay, and Western blotting analysis. It was found that (1) at therapeutic (50 microg/ml) and double therapeutic (100 microg/ml) concentrations, CP did not significantly affect normal DNA synthesis and cell growth in these cardiac cells, while at higher (over 4-fold therapeutic) concentrations (200-800 microg/ml), CP decreased DNA synthesis and cell growth and increased cell death; (2) CP treatment (50 microg/ml) significantly inhibited TNFalpha-induced apoptosis in myocytes, with 12.3+/-1.46% cells being apoptosis in CP treatment group and 37.0+/-7.34% in the control (pSalvia miltiorrhiza preparation CP is physiologically active on cardiac cells. The actions by CP to reduce apoptotic damage in myocytes and collagen synthesis in fibroblasts may help to preserve the heart function and reduce heart failure risk. The actions by CP to inhibit DNA synthesis and cell growth, which occurred at over therapeutic doses, may weaken the ability of heart repair. Further

  1. Fibroma of the flexor hallucis longus tendon sheath.

    Science.gov (United States)

    Kim, Sang Wha; Lee, So Young; Jung, Sung-No; Sohn, Won Il; Kwon, Ho

    2012-01-01

    Fibroma of tendon sheath is a rare benign tumor that usually occurs in upper extremities. It is mostly asymptomatic and grows slowly within the tendons or tendon sheaths. Histopathologic findings show well-demarcated nodules consisting of haphazardly arranged fibroblast-like spindle cells, which are embedded in a dense, collagenous matrix. We present a patient with fibroma of the tendon sheath on the flexor hallucis longus tendon, which was in an unusual location and has never been reported. The lesion was completely excised and showed no evidence of recurrence after 2 years of follow-up. Copyright © 2012 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Peroneal Tendon Injuries

    Science.gov (United States)

    ... the type of peroneal tendon injury. Options include: Immobilization. A cast or splint may be used to ... arthritis, gout, tendonitis, fracture, nerve compression (tarsal tunnel syndrome), infection and... Founded in 1942, the American College ...

  3. Chronic Achilles Tendon Rupture

    Science.gov (United States)

    Maffulli, Nicola; Via, Alessio Giai; Oliva, Francesco

    2017-01-01

    Background: The Achilles tendon, the largest and strongest tendon in the human body, is nevertheless one of the tendons which most commonly undergoes a complete subcutaneous tear. Achilles tendon ruptures are especially common in middle aged men who occasionally participate in sport. Even though Achilles tendon ruptures are frequent, up to 25% of acute injuries are misdiagnosed, and present as chronic injuries. Methods: This is a review article about diagnosis and management of chronic Achilles tendon ruptures. Minimally invasive Achilles tendon reconstruction is discussed. Results: The optimal surgical procedure is still debated, however, less invasive peroneus brevis reconstruction technique and free hamstring autograft provide good functional results. Conclusion: The management of chronic ruptures is more demanding than acute tears, because of the retraction of the tendon ends, and the gap makes primary repair impossible. Wound complications and infections are frequent after open procedures. Minimally invasive treatments provide good functional results and lower complications rate. PMID:29081863

  4. Collagen a natural scaffold for biology and engineering

    Science.gov (United States)

    Collagen, the most abundant protein in mammals, constitutes a quarter of the animal's total weight. The unique structure of fibrous collagens, a long triple helix that further associates into fibers, provides an insoluble scaffold that gives strength and form to the skin, tendons, bones, cornea and...

  5. The collagen microfibril model, a tool for biomaterials scientists

    Science.gov (United States)

    Animal hides, a major byproduct of the meat industry, are a rich source of collagen, a structural protein of the extracellular matrix that gives strength and form to the skin, tendons and bones of mammals. The structure of fibrous collagen, a long triple helix that self-associates in a staggered arr...

  6. Biomechanical analysis of partial flexor tendon lacerations in zone II of human cadavers.

    Science.gov (United States)

    Manning, David W; Spiguel, Andre R; Mass, Daniel P

    2010-01-01

    The aims of this study were to examine nonrepaired 90% partial lacerations of human cadaver flexor digitorum profundus (FDP) tendon after simulated active motion, and to assess the residual ultimate tensile strength. Partial, transverse zone II flexor tendon lacerations were made in the volar 90% of the tendon substance in 10 FDP tendons from 5 fresh-frozen human cadaver hands. The tendons were cycled in the curvilinear fashion described by Greenwald 500 times to a tension 25% greater than the maximum in vivo active FDP flexion force measured by Schuind and colleagues. The tendons were then loaded to failure using the same curvilinear model. No tendons ruptured during cycling. Triggering occurred in 3 tendons. All 3 began triggering early in the cycling process, and continued to trigger throughout the remainder of the 500 cycles. The observed triggering mechanics in each case involved the interaction of the proximal face of the lacerated tendon with Camper's chiasm and the pulley edges during extension. The load to failure value of the 90% partially lacerated tendons averaged 141.7 +/- 13 N (mean +/- standard deviation). Tendon failure occurred by delamination of the intact collagen fibers from the distal, discontinuous 90% of the tendon. Cadaveric transverse zone II partial flexor tendon lacerations have residual tensile strength greater than the force required for protected active mobilization. Copyright 2010. Published by Elsevier Inc.

  7. Postinjury biomechanics of Achilles tendon vary by sex and hormone status

    Science.gov (United States)

    Fryhofer, George W.; Freedman, Benjamin R.; Hillin, Cody D.; Salka, Nabeel S.; Pardes, Adam M.; Weiss, Stephanie N.; Farber, Daniel C.

    2016-01-01

    Achilles tendon ruptures are common injuries. Sex differences are present in mechanical properties of uninjured Achilles tendon, but it remains unknown if these differences extend to tendon healing. We hypothesized that ovariectomized females (OVX) and males would exhibit inferior postinjury tendon properties compared with females. Male, female, and OVX Sprague-Dawley rats (n = 32/group) underwent acclimation and treadmill training before blunt transection of the Achilles tendon midsubstance. Injured hindlimbs were immobilized for 1 wk, followed by gradual return to activity and assessment of active and passive hindlimb function. Animals were euthanized at 3 or 6 wk postinjury to assess tendon structure, mechanics, and composition. Passive ankle stiffness and range of motion were superior in females at 3 wk; however, by 6 wk, passive and active function were similar in males and females but remained inferior in OVX. At 6 wk, female tendons had greater normalized secant modulus, viscoelastic behavior, and laxity compared with males. Normalized secant modulus, cross-sectional area and tendon glycosaminoglycan composition were inferior in OVX compared with females at 6 wk. Total fatigue cycles until tendon failure were similar among groups. Postinjury muscle fiber size was better preserved in females compared with males, and females had greater collagen III at the tendon injury site compared with males at 6 wk. Despite male and female Achilles tendons withstanding similar durations of fatigue loading, early passive hindlimb function and tendon mechanical properties, including secant modulus, suggest superior healing in females. Ovarian hormone loss was associated with inferior Achilles tendon healing. PMID:27633741

  8. Direct Repair of Chronic Achilles Tendon Ruptures Using Scar Tissue Located Between the Tendon Stumps.

    Science.gov (United States)

    Yasuda, Toshito; Shima, Hiroaki; Mori, Katsunori; Kizawa, Momoko; Neo, Masashi

    2016-07-20

    Several surgical procedures for chronically ruptured Achilles tendons have been reported. Resection of the interposed scar tissue located between the tendon stumps and reconstruction using normal autologous tissue have been well described. We developed a direct repair procedure that uses scar tissue, which obviates the need to use normal autologous tissue. Thirty consecutive patients with Achilles tendon ruptures with a delay in diagnosis of >4 weeks underwent removal of a section of scar and healing tissue with direct primary suture of the ends of the tendon without the use of allograft or autograft. Patients were followed for a mean time of 33 months. Preoperative and postoperative clinical outcomes were measured with the Achilles Tendon Total Rupture Score (ATRS) and the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score. In addition, the patients underwent preoperative and postoperative functional measurements and magnetic resonance imaging. Lastly, we evaluated the histology of the interposed healing tissue. The mean AOFAS scores were 82.8 points preoperatively and 98.1 points postoperatively. The mean postoperative ATRS was 92.0 points. At the time of the latest follow-up, none of the patients had experienced tendon reruptures or difficulties in walking or climbing stairs, and all except 2 patients could perform a single-limb heel rise. All athletes had returned to their pre-injury level of sports participation. Preoperative T2-weighted magnetic resonance imaging showed that 22 Achilles tendons were thickened with diffuse intratendinous high-signal alterations, and 8 Achilles tendons were thinned. Postoperative T2-weighted magnetic resonance imaging findings included fusiform-shaped tendon thickening and homogeneous low-signal alterations of the tendons in all patients. Histologically, the interposed scar tissue consisted of dense collagen fibers. Shortening of the tissue between the 2 tendon ends that included healing scar and direct

  9. Biologics for tendon repair☆

    Science.gov (United States)

    Docheva, Denitsa; Müller, Sebastian A.; Majewski, Martin; Evans, Christopher H.

    2015-01-01

    Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation. Therapeutic options used to repair ruptured tendons have consisted of suture, autografts, allografts, and synthetic prostheses. To date, none of these alternatives has provided a successful long-term solution, and often the restored tendons do not recover their complete strength and functionality. Unfortunately, our understanding of tendon biology lags far behind that of other musculoskeletal tissues, thus impeding the development of new treatment options for tendon conditions. Hence, in this review, after introducing the clinical significance of tendon diseases and the present understanding of tendon biology, we describe and critically assess the current strategies for enhancing tendon repair by biological means. These consist mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage. A deeper understanding of how tendon tissue and cells operate, combined with practical applications of modern molecular and cellular tools could provide the long awaited breakthrough in designing effective tendon-specific therapeutics and overall improvement of tendon disease management. PMID:25446135

  10. Immunostimulatory effects of collagen from jellyfish in vivo.

    Science.gov (United States)

    Morishige, Hitoshi; Sugahara, Takuya; Nishimoto, Sogo; Muranaka, Ayako; Ohno, Fumi; Shiraishi, Ryusuke; Doi, Mikiharu

    2011-10-01

    We focused on the biological activity of the collagen extracts obtained from the giant edible jellyfish, Nemopilema nomurai. Jellyfish collagen extracts stimulates the production of immunoglobulins (Igs) and cytokines by human hybridoma cells and human peripheral blood lymphocytes. Therefore, we examined the immunoregulatory function of jellyfish collagen extracts in mice. Intake of jellyfish collagen extracts facilitated the Ig production activity of lymphocytes from spleen and Peyer's patch. Furthermore, the levels of Igs in the serum clearly increased after the administration of jellyfish collagen extracts. Intake of bovine collagen from Achilles' tendon also activated lymphocytes activity in mice. The activity of total and antigen-specific Ig production in splenocytes from OVA-challenged mice was also enhanced by collagen intake. However, the total and OVA-specific IgE levels in the serum were not affected by the collagen intake. These results suggested that jellyfish collagen extracts stimulates an immune response in vivo, without inducing allergic complications.

  11. Urotensin II contributes to collagen synthesis and up-regulates Egr-1 expression in cultured pulmonary arterial smooth muscle cells through the ERK1/2 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wei [Biomedical Engineering Institute, School of Control Science and Engineering, Shandong University, Jinan 250061 (China); Cai, Zhifeng; Liu, Mengmeng [Department of Pediatrics, Qilu Hospital, Shandong University, Jinan 250012 (China); Zhao, Cuifen, E-mail: zhaocuifen@sdu.edu.cn [Department of Pediatrics, Qilu Hospital, Shandong University, Jinan 250012 (China); Li, Dong [Research Room of Hypothermia Medicine, Qilu Hospital, Shandong University, Jinan 250012 (China); Lv, Chenguang; Wang, Yuping; Xu, Tengfei [Biomedical Engineering Institute, School of Control Science and Engineering, Shandong University, Jinan 250061 (China)

    2015-11-27

    Aim: The objective of this study was to investigate the effects of urotensin II (UII) treatment on the proliferation and collagen synthesis of cultured rat pulmonary arterial smooth muscle cells (PASMCs) and to explore whether these effects are mediated by mitogen-activated protein kinase (MAPK) signaling pathways and early growth response 1 (Egr-1). Methods: The proliferation of cultured PASMCs stimulated with different doses of UII was detected by BrdU incorporation. The mRNA expression levels of procollagen I (procol I), procollagen III (procol III), extracellular regulated protein kinase 1/2 (ERK1/2), stress-stimulated protein kinase (Sapk), p38 MAPK (p38), and Egr-1 mRNA in cultured PASMCs after treatment with UII, the UII-specific antagonist urantide, and the ERK1/2 inhibitor PD98059 were detected by real-time polymerase chain reaction (PCR), and the protein expression levels of procol I, procol III, phosphorylated (p)-ERK1/2, p-Sapk, p-p38, and Egr-1 were detected by Western blotting. Results: Treatment with UII increased the proliferation of cultured PASMCs in a dose-dependent manner (P < 0.05). However, treatment with urantide and PD98059 inhibited the promoting effect of UII on PASMC proliferation (P < 0.05). Real-time PCR analysis showed that UII up-regulated the expression of procol I, procol III, ERK1/2, Sapk, and Egr-1 mRNA (P < 0.05), but not p38 mRNA. However, the up-regulating effect of UII was inhibited by PD98059 and urantide. Western blotting analysis showed that UII increased the synthesis of collagen I, collagen III, p-ERK1/2, p-Sapk, and Egr-1, and these effects also were inhibited by PD98059 and urantide (P < 0.05). Conclusions: Egr-1 participates in the UII-mediated proliferation and collagen synthesis of cultured rat PASMCs via activation of the ERK1/2 signaling pathway.

  12. Effect of recombinant human growth hormone and interferon gamma on hepatic collagen synthesis and proliferation of hepatic stellate cells in cirrhotic rats.

    Science.gov (United States)

    Chen, Yong-Hua; Du, Bing-Qing; Zheng, Zhen-Jiang; Xiang, Guang-Ming; Liu, Xu-Bao; Mai, Gang

    2012-06-01

    Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10(-3)-10(-1) mg/100 μL), and interferon gamma (10(-2)-10(-1) μg/100 μL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10(-1) μg/100 μL, P0.05) and a time-dependent manner (Pgrowth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.

  13. Isolation and biological characterization of tendon-derived stem cells from fetal bovine.

    Science.gov (United States)

    Yang, Jinjuan; Zhao, Qianjun; Wang, Kunfu; Liu, Hao; Ma, Caiyun; Huang, Hongmei; Liu, Yingjie

    2016-09-01

    The lack of appropriate candidates of cell sources for cell transplantation has hampered efforts to develop therapies for tendon injuries, such as tendon rupture, tendonitis, and tendinopathy. Tendon-derived stem cells (TDSCs) are a type of stem cells which may be used in the treatment of tendon injuries. In this study, TDSCs were isolated from 5-mo-old Luxi Yellow fetal bovine and cultured in vitro and further analyzed for their biological characteristics using immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR) assays. It was found that primary TDSCs could be expanded for 42 passages in vitro maintaining proliferation. The expressions of stem cell marker nucleostemin and tenocyte-related markers, such as collagen I, collagen II, collagen III, and tenascin-C, were observed on different passage cells by immunofluorescence. The results from RT-PCR show that TDSCs were positive for collagen type I, CD44, tenascin-C, and collagen type III but negative for collagen type II. Meanwhile, TDSC passage 4 was successfully induced to differentiate into osteoblasts, adipocytes, and chondrocytes. Our results indicate that the fetal bovine TDSCs not only had strong self-renewal capacity but also possess the potential for multi-lineage differentiation. This study provides theoretical basis and experimental foundation for potential therapeutic application of the fetal bovine TDSCs in the treatment of tendon injuries.

  14. Tendon Tissue Engineering and Its Role on Healing of the Experimentally Induced Large Tendon Defect Model in Rabbits: A Comprehensive In Vivo Study

    Science.gov (United States)

    Meimandi-Parizi, Abdolhamid; Oryan, Ahmad; Moshiri, Ali

    2013-01-01

    Healing of large tendon defects is challenging. We studied the role of collagen implant with or without polydioxanone (PDS) sheath on the healing of a large Achilles tendon defect model, in rabbits. Sixty rabbits were divided into three groups. A 2 cm gap was created in the left Achilles tendon of all rabbits. In the control lesions, no implant was used. The other two groups were reconstructed by collagen and collagen-PDS implants respectively. The animals were clinically examined at weekly intervals and their lesions were observed by ultrasonography. Blood samples were obtained from the animals and were assessed for hematological analysis and determination of serum PDGF level, at 60 days post injury (DPI). The animals were then euthanized and their lesions were assessed for gross and histopathology, scanning electron microscopy, biomechanical testing, dry matter and hydroxyproline content. Another 65 pilot animals were also studied grossly and histopathologically to define the host implant interaction and graft incorporation at serial time points. The treated animals gained significantly better clinical scoring compared to the controls. Treatment with collagen and collagen-PDS implants significantly increased the biomechanical properties of the lesions compared to the control tendons at 60DPI (Plesions (Ptendon. Implantation of the bioimplants had a significant role in initiating tendon healing and the implants were biocompatible, biodegradable and safe for application in tendon reconstructive surgery. The results of the present study may be valuable in clinical practice. PMID:24039851

  15. Down-regulation of collagen synthesis and matrix metalloproteinase expression in myofibroblasts from Dupuytren nodule using adenovirus-mediated relaxin gene therapy.

    Science.gov (United States)

    Kang, Young-Mi; Choi, Yun-Rak; Yun, Chae-Ok; Park, Jin-Oh; Suk, Kyung-Soo; Kim, Hak-Sun; Park, Moon-Soo; Lee, Byung-Ho; Lee, Hwan-Mo; Moon, Seong-Hwan

    2014-04-01

    Dupuytren's disease is a fibroproliferative connective tissue disorder characterized by contracture of the palmer fascia of the hand. Relaxin (RLN) is a multifunctional factor which contributes to the remodeling of the pelvic ligament by inhibiting fibrosis and inflammatory activities. The aim of this study was to investigate the effect of the RLN gene on the inhibition of fibrosis in myofibroblastic cells. Myofibroblast cells with adenovirus LacZ (Ad-LacZ) as a marker gene or adenovirus relaxin (Ad-RLN) as therapeutic gene showed transgene expressions in beta-galactosidase assay and Western blot analysis. Myofibroblastic cells with Ad-RLN demonstrated a 22% and 48% reduction in collagen I and III mRNA expressions respectively, a 50% decrease in MMP-1, 70% decrease in MMP-2, 80% decrease in MMP-9, and a 15% reduction in MMP-13 protein expression compared with cultures with viral control and saline control. In addition, myofibroblastic cells with Ad-RLN showed a 40% decrease in TIMP 1 and a 15% increase in TIMP 3 protein expression at 48 h compared to cultures with viral control and saline control. Also, myofibroblastic cell with Ad-RLN demonstrated a 74% inhibition of fibronectin and a 52% decrease in total collagen synthesis at 48 h compared with cultures with viral control and saline control. In conclusion, the RLN gene render antifibrogenic effect on myofibroblastic cells from Dupuytren's nodule via direct inhibition of collagen synthesis not through collagenolytic pathway such as MMP-1, -13, TIMP 1, and 3. Therefore relaxin can be an alternative therapeutic strategy in initial stage of Dupuytren's disease by its antifibrogenic effect. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  16. Training-induced changes in peritendinous type I collagen turnover determined by microdialysis in humans

    DEFF Research Database (Denmark)

    Langberg, Henning; Rosendal, L; Kjaer, M

    2001-01-01

    1. Acute exercise is found to increase collagen type I formation locally in peritendinous connective tissue of the Achilles' tendon in humans, as determined from changes in interstitial concentrations of collagen propeptide (PICP) and a collagen degradation product (ICTP) by the use of microdialy...

  17. Molecular basis for elastic energy storage in mineralized tendon.

    Science.gov (United States)

    Silver, F H; Freeman, J W; Horvath, I; Landis, W J

    2001-01-01

    Animals store elastic energy in leg and foot tendons during locomotion. In the turkey, much of the locomotive force generated by the gastrocnemius muscle is stored as elastic energy during tendon deformation. Little energy storage occurs within the muscle. During growth of some avians, including the turkey, leg tendons mineralize in the portions distal to the attached muscle and show increased tensile strength and modulus as a result. The purpose of this study is to test the hypothesis that the degree of elastic energy storage in mineralizing turkey tendon is directly related to the tendon mineral content. To test this hypothesis, the stress-strain behavior of tendons was separated into elastic and viscous components. Both the elastic spring constant and the elastic energy stored, calculated up to a strain of 20%, were found to be proportional to tendon mineral content. It is concluded that mineralization is an efficient means for increasing the amount of elastic energy storage that is required for increased load-bearing ability needed for locomotion of adult birds. Examination of molecular models of the hole region, where mineralization is initiated within the collagen fibril, leads to the hypothesis that elastic energy is stored in the tendon by direct stretching of the flexible regions. Flexible regions within the collagen molecule fall within the positively stained bands of the collagen D period. It is proposed that mineralization increases the stored elastic energy by preventing flexible regions within the positively stained bands from stretching. These observations suggest that mineralization begins in the hole region due to the large number of charged amino acid residues found in the d and e bands.

  18. Adaptive Remodeling of Achilles Tendon: A Multi-scale Computational Model

    Science.gov (United States)

    Rubenson, Jonas; Umberger, Brian

    2016-01-01

    While it is known that musculotendon units adapt to their load environments, there is only a limited understanding of tendon adaptation in vivo. Here we develop a computational model of tendon remodeling based on the premise that mechanical damage and tenocyte-mediated tendon damage and repair processes modify the distribution of its collagen fiber lengths. We explain how these processes enable the tendon to geometrically adapt to its load conditions. Based on known biological processes, mechanical and strain-dependent proteolytic fiber damage are incorporated into our tendon model. Using a stochastic model of fiber repair, it is assumed that mechanically damaged fibers are repaired longer, whereas proteolytically damaged fibers are repaired shorter, relative to their pre-damage length. To study adaptation of tendon properties to applied load, our model musculotendon unit is a simplified three-component Hill-type model of the human Achilles-soleus unit. Our model results demonstrate that the geometric equilibrium state of the Achilles tendon can coincide with minimization of the total metabolic cost of muscle activation. The proposed tendon model independently predicts rates of collagen fiber turnover that are in general agreement with in vivo experimental measurements. While the computational model here only represents a first step in a new approach to understanding the complex process of tendon remodeling in vivo, given these findings, it appears likely that the proposed framework may itself provide a useful theoretical foundation for developing valuable qualitative and quantitative insights into tendon physiology and pathology. PMID:27684554

  19. Collagen in organ development

    Science.gov (United States)

    Hardman, P.; Spooner, B. S.

    1992-01-01

    It is important to know whether microgravity will adversely affect developmental processes. Collagens are macromolecular structural components of the extracellular matrix (ECM) which may be altered by perturbations in gravity. Interstitial collagens have been shown to be necessary for normal growth and morphogenesis in some embryonic organs, and in the mouse salivary gland, the biosynthetic pattern of these molecules changes during development. Determination of the effects of microgravity on epithelial organ development must be preceded by crucial ground-based studies. These will define control of normal synthesis, secretion, and deposition of ECM macromolecules and the relationship of these processes to morphogenesis.

  20. Effects of estrogen replacement and lower androgen status on skeletal muscle collagen and myofibrillar protein synthesis in postmenopausal women

    DEFF Research Database (Denmark)

    Hansen, M; Skovgaard, D; Reitelseder, S

    2012-01-01

    myofibrillar protein FSR only in ERT users. Similarly, muscle collagen FSR tended to be lower in ERT users compared with Controls. In ERT participants, the androgen profile was reduced, whereas estradiol and sex hormone-binding globulin were higher. In conclusion, at rest, myofibrillar protein FSR was lower...

  1. Collagenous hydrolysates from untraditional sources of proteins.

    Science.gov (United States)

    Langmaier, F; Mladek, M; Kolomaznik, K; Sukop, S

    2001-08-01

    Sufficiently pure collagenous hydrolysates, suitable for application in skin and hair care cosmetics, have been prepared through biotechnological methods with the use of commercially available enzymatic preparations from short cattle tendons (musculus extensor communis, musculus flexor digitorum, musculus flexor digitorum profundis). These hydrolysates contain neither lipoid nor aminosaccharide components, content of primary amino groups reaches around 1.1 mmol g(-1) and the average molecular weight of the resulting collagenous hydrolysates does not exceed 2000 g mol(-1) (2.0 kDa). Short cattle tendons represent a relatively pure and easily available source of collagens and are, despite their generally known low nutritional value, used only as a feeding mixture component.

  2. Spontaneous rupture of the long head of the biceps tendon in a woman with hypothyroidism: a case report.

    Science.gov (United States)

    Pantazis, K; Roupas, N D; Panagopoulos, Andreas; Theodoraki, S; Tsintoni, A; Kyriazopoulou, V

    2016-01-13

    Tendinitis can be a presenting complaint in hypothyroidism, with symptomatic relief being obtained by appropriate management of the primary thyroid deficiency. To the best of our knowledge no other cases of spontaneous rupture of the long head of the biceps tendon during uncontrolled hypothyroidism have yet been reported. This case report describes an unusual case of spontaneous rupture of the long head of the biceps tendon in a 48-year-old white woman with severe hypothyroidism. She described experiencing a sudden sharp pain and an audible pop in her right shoulder while using her personal computer. On physical examination she was positive for Yergason's sign and a subsequent magnetic resonance imaging scan showed complete rupture of the long head of her biceps tendon. Laboratory tests revealed significantly elevated thyrotropin levels (>100 μIU/ml) and very low levels of both triiodothyronine (0.17 ng/ml) and free thyroxine (0.18 ng/dl). She was switched to a different thyroxin regimen with a progressive dosage increment. She declined surgical re-anchorage of the tendon but despite the discreet Popeye sign, her overall strength and shoulder function were satisfactory. After 2 months, she was found to be clinically euthyroid, having normal thyroid function tests (thyrotropin 2.95 μIU/mL, free thyroxine 1.07 ng/dl). At her last follow-up visit, 1 year post-injury, she reported nearly normal shoulder function in her daily activities and had a constant shoulder score of 93 points. The role of thyroid hormones in the synthesis and degeneration of collagen and in the proliferation and apoptosis of human tenocytes is discussed, providing a possible mechanism whereby hypothyroidism may lead to tendon tears. This report may have a greater impact among different subspecialties as it presupposes a high degree of awareness from internists, endocrinologists and orthopedic surgeons.

  3. Tendon protein synthesis rate in classic Ehlers-Danlos patients can be stimulated with insulin-like growth factor-I

    DEFF Research Database (Denmark)

    Nielsen, Rie Harboe; Holm, Lars; Jensen, Jacob Kildevang

    2014-01-01

    The classic form of Ehlers-Danlos syndrome (cEDS) is an inherited connective tissue disorder, where mutations in type V collagen-encoding genes result in abnormal collagen fibrils. Thus the cEDS patients have pathological connective tissue morphology and low stiffness, but the rate of connective...

  4. Effects of transdermal estrogen on collagen turnover at rest and in response to exercise in postmenopausal women

    DEFF Research Database (Denmark)

    Pingel, Jessica; Langberg, Henning; Skovgård, D

    2012-01-01

    Menopause is associated with loss of collagen content in the skin and tendon as well as accumulation of noncontractile tissue in skeletal muscle. The relative role of hormones and physical activity on these changes is not known. Accordingly, in a randomized, controlled, crossover study we investi...... that the availability of estrogen in postmenopausal women is important for repair of muscle damage or remodeling of the connective tissue within the skeletal muscle after exercise....... loading and treatment P = 0.008). In neither skeletal muscle nor peritendinous fluid were IGF-I and IL-6 influenced by treatment or exercise. In conclusion, ERT was associated with enhanced synthesis of type I collagen in the skeletal muscle in response to acute exercise. In perspective, this indicates......Menopause is associated with loss of collagen content in the skin and tendon as well as accumulation of noncontractile tissue in skeletal muscle. The relative role of hormones and physical activity on these changes is not known. Accordingly, in a randomized, controlled, crossover study we...

  5. Tendon functional extracellular matrix.

    Science.gov (United States)

    Screen, Hazel R C; Berk, David E; Kadler, Karl E; Ramirez, Francesco; Young, Marian F

    2015-06-01

    This article is one of a series, summarizing views expressed at the Orthopaedic Research Society New Frontiers in Tendon Research Conference. This particular article reviews the three workshops held under the "Functional Extracellular Matrix" stream. The workshops focused on the roles of the tendon extracellular matrix, such as performing the mechanical functions of tendon, creating the local cell environment, and providing cellular cues. Tendon is a complex network of matrix and cells, and its biological functions are influenced by widely varying extrinsic and intrinsic factors such as age, nutrition, exercise levels, and biomechanics. Consequently, tendon adapts dynamically during development, aging, and injury. The workshop discussions identified research directions associated with understanding cell-matrix interactions to be of prime importance for developing novel strategies to target tendon healing or repair. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. Impact of TGF-β inhibition during acute exercise on Achilles tendon extracellular matrix

    DEFF Research Database (Denmark)

    Potter, Ross M; Huynh, Richard T; Volper, Brent D

    2017-01-01

    The purpose of this study was to evaluate the role of TGF-β1 in regulating tendon extracellular matrix after acute exercise. Wistar rats exercised (n = 15) on a treadmill for four consecutive days (60 min/day) or maintained normal cage activity. After each exercise bout, the peritendinous space...... of each Achilles tendon was injected with a TGF-β1 receptor inhibitor or sham. Independent of group, tendons injected with inhibitor exhibited ~50% lower Smad 3 (Ser423/425) (P ... not alter collagen content in either group (P > 0.05). In exercised rats, hydroxylyslpyridinoline content and collagen III expression were lower (P tendons injected with inhibitor when compared with sham. In nonexercised rats, collagen I and lysyl oxidase (LOX) expression was lower (P

  7. Glutaraldehyde Cross-Linking of TendonMechanical Effects at the Level of the Tendon Fascicle and Fibril

    DEFF Research Database (Denmark)

    Hansen, P.; Svensson, R.B.; Aagaard, P.

    2009-01-01

    Conclusive insight into the microscopic principles that govern the strength of tendon and related connective tissues is lacking and the importance of collagen cross-linking has not been firmly established. The combined application of whole-tissue mechanical testing and atomic force spectroscopy...

  8. Percutaneous Achilles Tendon Lengthening

    Science.gov (United States)

    ... Ligament Reconstruction Lateral Ankle Stabilization Mosaicplasty for Osteochondral Lesions of the Talus Peroneus Longus to Achilles Tendon Transfer Pilon Fracture Surgery Posterior Ankle Endoscopy or ...

  9. Imaging Collagen in Scar Tissue: Developments in Second Harmonic Generation Microscopy for Biomedical Applications.

    Science.gov (United States)

    Mostaço-Guidolin, Leila; Rosin, Nicole L; Hackett, Tillie-Louise

    2017-08-15

    The ability to respond to injury with tissue repair is a fundamental property of all multicellular organisms. The extracellular matrix (ECM), composed of fibrillar collagens as well as a number of other components is dis-regulated during repair in many organs. In many tissues, scaring results when the balance is lost between ECM synthesis and degradation. Investigating what disrupts this balance and what effect this can have on tissue function remains an active area of research. Recent advances in the imaging of fibrillar collagen using second harmonic generation (SHG) imaging have proven useful in enhancing our understanding of the supramolecular changes that occur during scar formation and disease progression. Here, we review the physical properties of SHG, and the current nonlinear optical microscopy imaging (NLOM) systems that are used for SHG imaging. We provide an extensive review of studies that have used SHG in skin, lung, cardiovascular, tendon and ligaments, and eye tissue to understand alterations in fibrillar collagens in scar tissue. Lastly, we review the current methods of image analysis that are used to extract important information about the role of fibrillar collagens in scar formation.

  10. Effect of indomethacin and lactoferrin on human tenocyte proliferation and collagen formation in vitro.

    Science.gov (United States)

    Zhang, Yaonan; Wang, Xiao; Qiu, Yiwei; Cornish, Jillian; Carr, Andrew J; Xia, Zhidao

    2014-11-14

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in patients with injuries and inflammation of tendon and ligament, and as post-surgical analgesics. The aim of this study is to investigate the effect of indomethacin, a classic NSAID and its combinational effect with an anabolic agent of skeletal tissue, lactoferrin, on the proliferation and collagen formation of human tenocytes in vitro. A factorial experimental design was employed to study the dose-dependent effect of the combination of indomethacin and lactoferrin. The results showed that indomethacin at high concentration (100 μM) inhibited human tenocyte proliferation in culture medium with 1-10% fetal bovine serum (FBS) in vitro. Also, high dose of indomethacin inhibited the collagen formation of human tenocytes in 1% FBS culture medium. Lactoferrin at 50-100 μg/ml promoted human tenocyte survival in serum-free culture medium and enhanced proliferation and collagen synthesis of human tenocytes in 1% FBS culture medium. When 50-100 μg/ml lactoferrin was used in combination with 100-200 μM indomethacin, it partially rescued the inhibitory effects of indomethacin on human tenocyte proliferation, viability and collagen formation. To our knowledge, it is the first evidence that lactoferrin is anabolic to human tenocytes in vitro and reverses potential inhibitory effects of NSAIDs on human tenocytes. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Synthesis, characterization and comparison of antimicrobial activity of PEG/TritonX-100 capped silver nanoparticles on collagen scaffold.

    Science.gov (United States)

    Mandal, A; Meda, V; Zhang, W J; Farhan, K M; Gnanamani, A

    2012-02-01

    Silver nanoparticles have received attention as novel antimicrobial agents. In order to study the effects of silver nanoparticles on both Gram positive and negative bacteria, the nanoparticles were synthesized via chemical reduction method using different concentrations (0.3, 0.6 and 0.9 mM) of poly(ethylene) glycol (PEG) and TritonX-100 (TX). Also, mixed PEG/TX systems with equimolar concentrations capped silver nanoparticles were synthesized and confirmed by UV-vis, fluorescence spectroscopy and particle size analysis. These coated silver nanoparticles were incorporated into collagen, lyophilized to form scaffolds and characterized by SEM, XRD, ATR-FTIR, DSC, TGA and zeta potential. Results on mechanical property of all the scaffolds displayed no significant difference in the percentage elongation at break. However, the maximum percentage of 46.67% was observed with the combinations (0.9 mM PEG+0.9 mM TX). This implies that the combinations of surfactants increase the elasticity, which is useful for biomedical applications, e.g., heart-valve preparations. Furthermore, the antimicrobial activities of these capped silver nanoparticles homogenized with collagen were tested against both Gram positive and negative bacteria. Minimum inhibitory concentration values obtained for the combination (0.9 mM PEG+0.9 mM TX) were found to be better than others and thus provide strong antibacterial property to the collagen scaffolds prepared for tissue regeneration applications. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Tendon tissue engineering and its role on healing of the experimentally induced large tendon defect model in rabbits: a comprehensive in vivo study.

    Directory of Open Access Journals (Sweden)

    Abdolhamid Meimandi-Parizi

    Full Text Available Healing of large tendon defects is challenging. We studied the role of collagen implant with or without polydioxanone (PDS sheath on the healing of a large Achilles tendon defect model, in rabbits. Sixty rabbits were divided into three groups. A 2 cm gap was created in the left Achilles tendon of all rabbits. In the control lesions, no implant was used. The other two groups were reconstructed by collagen and collagen-PDS implants respectively. The animals were clinically examined at weekly intervals and their lesions were observed by ultrasonography. Blood samples were obtained from the animals and were assessed for hematological analysis and determination of serum PDGF level, at 60 days post injury (DPI. The animals were then euthanized and their lesions were assessed for gross and histopathology, scanning electron microscopy, biomechanical testing, dry matter and hydroxyproline content. Another 65 pilot animals were also studied grossly and histopathologically to define the host implant interaction and graft incorporation at serial time points. The treated animals gained significantly better clinical scoring compared to the controls. Treatment with collagen and collagen-PDS implants significantly increased the biomechanical properties of the lesions compared to the control tendons at 60DPI (P<0.05. The tissue engineered implants also reduced peritendinous adhesion, muscle fibrosis and atrophy, and increased ultrasonographical echogenicity and homogenicity, maturation and differentiation of the collagen fibrils and fibers, tissue alignment and volume of the regenerated tissue compared to those of the control lesions (P<0.05. The implants were gradually absorbed and substituted by the new tendon. Implantation of the bioimplants had a significant role in initiating tendon healing and the implants were biocompatible, biodegradable and safe for application in tendon reconstructive surgery. The results of the present study may be valuable in

  13. The study of optical properties and proteoglycan content of tendons by PS-OCT

    Science.gov (United States)

    Yang, Ying; Rupani, Asha; Weightman, Alan; Wimpenny, Ian; Bagnaninchi, Pierre; Ahearne, Mark

    2011-03-01

    Tendons are load-bearing collagenous tissues consisting mainly of type I collagen and various proteoglycans (PGs) including decorin and versican. It is widely accepted that highly orientated collagen fibers in tendons a play critical role for transferring tensile stress and demonstrate birefringent optical properties. However, the influence that proteoglycans have on the optical properties of tendons is yet to be fully elucidated. Tendinopathy (defined as a syndrome of tendon pain, tenderness and swelling that affects the normal function of the tissue) is a common disease associated with sporting injuries or degeneration. PG's are the essential components of the tendon extracellular matrix; changes in their quantities and compositions have been associated with tendinopathy. In this study, polarization sensitive optical coherence tomography (PS-OCT) has been used to reveal the relationship between proteoglycan content/location and birefringent properties of tendons. Tendons dissected from freshly slaughtered chickens were imaged at regular intervals by PS-OCT and polarizing light microscope during the extraction of PGs or glycosaminoglycans using established protocols (guanidine hydrochloride (GuHCl) or proteinase K solution). The macroscopic and microscopic time lapsed images are complimentary; mutually demonstrating that there was a higher concentration of PG's in the outer sheath region than in the fascicles; and the integrity of the sheath affected extraction process and the OCT birefringence bands. Extraction of PGs using GuHCl disturbed the organization of local collagen bundles, which corresponded to a reduction in the frequency of birefringence bands and the band width by PS-OCT. The feature of OCT penetration depth helped us to define the heterogeneous distribution of PG's in tendon, which was complimented by polarizing light microscopy. The results provide new insight of tendon structure and also demonstrate a great potential for using PS-OCT as a

  14. Distinct post-translational features of type I collagen are conserved in mouse and human periodontal ligament.

    Science.gov (United States)

    Hudson, D M; Garibov, M; Dixon, D R; Popowics, T; Eyre, D R

    2017-12-01

    Specifics of the biochemical pathways that modulate collagen cross-links in the periodontal ligament (PDL) are not fully defined. Better knowledge of the collagen post-translational modifications that give PDL its distinct tissue properties is needed to understand the pathogenic mechanisms of human PDL destruction in periodontal disease. In this study, the post-translational phenotypes of human and mouse PDL type I collagen were surveyed using mass spectrometry. PDL is a highly specialized connective tissue that joins tooth cementum to alveolar bone. The main function of the PDL is to support the tooth within the alveolar bone while under occlusal load after tooth eruption. Almost half of the adult population in the USA has periodontal disease resulting from inflammatory destruction of the PDL, leading to tooth loss. Interestingly, PDL is unique from other ligamentous connective tissues as it has a high rate of turnover. Rapid turnover is believed to be an important characteristic for this specialized ligament to function within the oral-microbial environment. Like other ligaments, PDL is composed predominantly of type I collagen. Collagen synthesis is a complex process with multiple steps and numerous post-translational modifications including hydroxylation, glycosylation and cross-linking. The chemistry, placement and quantity of intermolecular cross-links are believed to be important regulators of tissue-specific structural and mechanical properties of collagens. Type I collagen was isolated from several mouse and human tissues, including PDL, and analyzed by mass spectrometry for post-translational variances. The collagen telopeptide cross-linking lysines of PDL were found to be partially hydroxylated in human and mouse, as well as in other types of ligament. However, the degree of hydroxylation and glycosylation at the helical Lys87 cross-linking residue varied across species and between ligaments. These data suggest that different types of ligament collagen

  15. Different Achilles Tendon Pathologies Show Distinct Histological and Molecular Characteristics

    Directory of Open Access Journals (Sweden)

    Franka Klatte-Schulz

    2018-01-01

    Full Text Available Reasons for the development of chronic tendon pathologies are still under debate and more basic knowledge is needed about the different diseases. The aim of the present study was therefore to characterize different acute and chronic Achilles tendon disorders. Achilles tendon samples from patients with chronic tendinopathy (n = 7, chronic ruptures (n = 6, acute ruptures (n = 13, and intact tendons (n = 4 were analyzed. The histological score investigating pathological changes was significantly increased in tendinopathy and chronic ruptures compared to acute ruptures. Inflammatory infiltration was detected by immunohistochemistry in all tendon pathology groups, but was significantly lower in tendinopathy compared to chronic ruptures. Quantitative real-time PCR (qRT-PCR analysis revealed significantly altered expression of genes related to collagens and matrix modeling/remodeling (matrix metalloproteinases, tissue inhibitors of metalloproteinases in tendinopathy and chronic ruptures compared to intact tendons and/or acute ruptures. In all three tendon pathology groups markers of inflammation (interleukin (IL 1β, tumor necrosis factor α, IL6, IL10, IL33, soluble ST2, transforming growth factor β1, cyclooxygenase 2, inflammatory cells (cluster of differentaition (CD 3, CD68, CD80, CD206, fat metabolism (fatty acid binding protein 4, peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, adiponectin, and innervation (protein gene product 9.5, growth associated protein 43, macrophage migration inhibitory factor were detectable, but only in acute ruptures significantly regulated compared to intact tendons. The study gives an insight into structural and molecular changes of pathological processes in tendons and might be used to identify targets for future therapy of tendon pathologies.

  16. Study of optical properties and proteoglycan content of tendons by polarization sensitive optical coherence tomography

    Science.gov (United States)

    Yang, Ying; Rupani, Asha; Bagnaninchi, Pierre; Wimpenny, Ian; Weightman, Alan

    2012-08-01

    The highly orientated collagen fibers in tendons play a critical role for transferring tensile stress, and they demonstrate birefringent optical properties. However, the influence that proteoglycans (PGs) have on the optical properties of tendons is yet to be fully elucidated. PGs are the essential components of the tendon extracellular matrix; the changes in their quantities and compositions have been associated with tendinopathies. In this study, polarization sensitive optical coherence tomography (PS-OCT) has been used to reveal the relationship between PG content/location and birefringence properties of tendons. Fresh chicken tendons were imaged at regular intervals by PS-OCT and polarization light microscopy during the extraction of PGs, using guanidine hydrochloride (GuHCl). Complementary time-lapsed images taken from the two modalities mutually demonstrated that the extraction of PGs disturbed the local organization of collagen bundles. This corresponded with a decrease in birefringence and associated banding pattern observed by PS-OCT. Furthermore, this study revealed there was a higher concentration of PGs in the outer sheath region than in the fascicles, and therefore the change in birefringence was reduced when extraction was performed on unsheathed tendons. The results provide new insights of tendon structure and the role of PGs on the structural stability of tendons, which also demonstrates the great potential for using PS-OCT as a diagnostic tool to examine tendon pathology.

  17. Microtopographically patterned surfaces promote the alignment of tenocytes and extracellular collagen.

    Science.gov (United States)

    Kapoor, Ashish; Caporali, Evelyn H G; Kenis, Paul J A; Stewart, Matthew C

    2010-07-01

    This paper investigates the role of microtopographical features on the cytomorphology, alignment, proliferation and gene expression of tenocytes. We made use of simple microfabrication approaches to create surfaces patterned with topographical features suitable for in vitro studies of tenocytes. These surfaces were composed of glass substrates patterned with polymeric ridges spaced from 50 to 250 microm apart. Our studies demonstrate that the microgrooves differentially impact tenocyte shape, alignment and matrix organization along the direction of grooves. Groove widths significantly influenced cellular alignment, with 50 microm grooved patterns affecting alignment most substantially. Polarized light microscopy demonstrated that mature collagen fibers were denser and more oriented within 50 microm patterns. None of the patterns had a significant effect on the expression of genes linked to proliferation or extracellular matrix synthesis, although time in culture profoundly influenced both gene groups. COMP mRNA expression was moderately increased in tenocytes seeded onto 250 microm grooves, but there was no overall beneficial phenotypic effect of aligned growth. The results of this study indicate that microtopography affects cell density and alignment of tenocytes and leads to the deposition of an aligned collagen matrix, but does not significantly impact matrix gene expression or cell phenotype. These outcomes provide insights into the biology of tendon regeneration, thus providing guidance in the design of clinical procedures for tendon repair. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  18. In vitro and in vivo research on using Antheraea pernyi silk fibroin as tissue engineering tendon scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Fang Qian [College of Life Sciences, Fujian Normal University, Fuzhou, Fujian350108 (China); Chen Denglong [College of Chemistry and Materials Sciences, Fujian Normal University, Fuzhou, Fujian350108 (China); Yang Zhiming [Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China); Li Min, E-mail: mli@fjnu.edu.cn [College of Life Sciences, Fujian Normal University, Fuzhou, Fujian350108 (China)

    2009-06-01

    In this paper, the feasibility of using Antheraea pernyi silk fibroin as tissue engineering tendon scaffold was investigated in vitro and in vivo, respectively, utilizing tenocytes and animal model. The animal model used here was an adult New Zealand White rabbit with a 15-mm gap defect in both sides of the Achilles tendon. The Achilles tendon defects in one side of hind legs were repaired using the braided A. pernyi silk fibroin scaffold in experimental group (n = 24), while the other side left untreated as negative group (n = 24). The recovery of the defect tendons were evaluated postoperatively at the 2nd, 6th, 12th, and 16th week using macroscopic, histological, immunohistochemical, scanning electron micrograph and biomechanical test techniques. In vitro results examined by scanning electron micrograph showed that A. pernyi silk fibroin promote the adhesion and propagation of the tenocytes. In vivo, at 16 weeks after implantation, morphological results showed that neo-tendons were formed, and bundles of collagen fibers in the neo-tendons were uniform and well oriented. Immunohistochemical results showed that collagen type in the regenerated tendons was predominantly type I. The maximum load of regenerated tendon at 16 weeks reached 55.46% of the normal tendon values. Preliminary, we concluded that A. pernyi silk fibroin promoted the recovery of Achilles tendon defect of rabbit and the application of A. pernyi silk fibroin as tissue engineering tendon scaffold is feasible.

  19. Collagenous sprue

    DEFF Research Database (Denmark)

    Soendergaard, Christoffer; Riis, Lene Buhl; Nielsen, Ole Haagen

    2014-01-01

    disease and together with frequent histological findings like mucosal thinning and intraepithelial lymphocytosis the diagnosis may be hard to reach without awareness of this condition. While coeliac disease is treated using gluten restriction, collagenous sprue is, however, not improved...... by this intervention. In cases of diet-refractory 'coeliac disease' it is therefore essential to consider collagenous sprue to initiate treatment at an early stage to prevent the fibrotic progression. Here, we report a case of a 78-year-old man with collagenous sprue and present the clinical and histological...

  20. Effect of indomethacin and lactoferrin on human tenocyte proliferation and collagen formation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yaonan [Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP (United Kingdom); Department of Orthopaedic, Beijing Hospital of Ministry of Public Health, Beijing, China 100730 (China); Wang, Xiao; Qiu, Yiwei [Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP (United Kingdom); Cornish, Jillian [Department of Medicine, University of Auckland, Private Bag 92019, Auckland (New Zealand); Carr, Andrew J. [Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP (United Kingdom); Xia, Zhidao, E-mail: z.xia@swansea.ac.uk [Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP (United Kingdom)

    2014-11-14

    Highlights: • Indomethacin, a classic NSAID, inhibited human tenocyte proliferation at high concentration (100 µM). • Lactoferrin at 50-100 µg/ml promoted human tenocyte survival, proliferation and collagen synthesis. • Lactoferrin is anabolic to human tenocytes in vitro and reverses potential inhibitory effects of NSAIDs on human tenocytes. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in patients with injuries and inflammation of tendon and ligament, and as post-surgical analgesics. The aim of this study is to investigate the effect of indomethacin, a classic NSAID and its combinational effect with an anabolic agent of skeletal tissue, lactoferrin, on the proliferation and collagen formation of human tenocytes in vitro. A factorial experimental design was employed to study the dose-dependent effect of the combination of indomethacin and lactoferrin. The results showed that indomethacin at high concentration (100 μM) inhibited human tenocyte proliferation in culture medium with 1–10% fetal bovine serum (FBS) in vitro. Also, high dose of indomethacin inhibited the collagen formation of human tenocytes in 1% FBS culture medium. Lactoferrin at 50–100 μg/ml promoted human tenocyte survival in serum-free culture medium and enhanced proliferation and collagen synthesis of human tenocytes in 1% FBS culture medium. When 50–100 μg/ml lactoferrin was used in combination with 100–200 μM indomethacin, it partially rescued the inhibitory effects of indomethacin on human tenocyte proliferation, viability and collagen formation. To our knowledge, it is the first evidence that lactoferrin is anabolic to human tenocytes in vitro and reverses potential inhibitory effects of NSAIDs on human tenocytes.

  1. Tendon lengthening and transfer.

    Science.gov (United States)

    Fitoussi, F; Bachy, M

    2015-02-01

    Tendon lengthening and transfer are usually indicated for certain neuromuscular disorders, peripheral or central nerve injury, congenital disorder or direct traumatic or degenerative musculotendinous lesion. In musculotendinous lengthening, technique depends on muscle anatomy, degree of correction required, and the need to avoid excessive loss of force. Lengthening within the muscle or aponeurosis is stable. In the tendon, however, it may provide greater gain but is not stable and requires postoperative immobilization to avoid excessive lengthening. Tendon transfer consists in displacing a muscle's tendon insertion in order to restore function. The muscle to be transferred is chosen according to strength, architecture and course, contraction timing, intended direction, synergy and the joint moment arm to be restored. Functions to be restored have to be prioritized, and alternatives to transfer should be identified. The principles of tendon transfer require preoperative assessment of the quality of the tissue through which the transfer is to pass and of the suppleness of the joints concerned. During the procedure, transfer tension should be optimized and the neurovascular bundle should be protected. The method of fixation, whether tendon-to-bone or tendon-to-tendon suture, should be planned according to local conditions and the surgeon's experience. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. The Healing Effects of Aquatic Activities and Allogenic Injection of Platelet-Rich Plasma (PRP) on Injuries of Achilles Tendon in Experimental Rat.

    Science.gov (United States)

    Rajabi, Hamid; Sheikhani Shahin, Homa; Norouzian, Manijeh; Mehrabani, Davood; Dehghani Nazhvani, Seifollah

    2015-01-01

    Clinical tendon injuries represent serious and unresolved issues of the case on how the injured tendons could be improved based on natural structure and mechanical strength. The aim of this studies the effect of aquatic activities and alogenic platelet rich plasma (PRP) injection in healing Achilles tendons of rats. Forty rats were randomly divided into 5 equal groups. Seventy two hours after a crush lesion on Achilles tendon, group 1 underwent aquatic activity for 8 weeks (five sessions per week), group 2 received intra-articular PRP (1 ml), group 3 had aquatic activity together with injection PRP injection after an experimental tendon injury, group 4 did not receive any treatment after tendon injury and the control group with no tendon injuries. of 32 rats. After 8 weeks, the animals were sacrificed and the tendons were transferred in 10% formalin for histological evaluation. There was a significant increase in number of fibroblast and cellular density, and collagen deposition in group 3 comparing to other groups denoting to an effective healing in injured tendons. However, there was no significant difference among the studied groups based on their tendons diameter. Based on our findings on the number of fibroblast, cellular density, collagen deposition, and tendon diameter, it was shown that aquatic activity together with PRP injection was the therapeutic measure of choice enhance healing in tendon injuries that can open a window in treatment of damages to tendons.

  3. Might the Masson trichrome stain be considered a useful method for categorizing experimental tendon lesions?

    Science.gov (United States)

    Martinello, Tiziana; Pascoli, Francesco; Caporale, Giovanni; Perazzi, Anna; Iacopetti, Ilaria; Patruno, Marco

    2015-08-01

    Strain injuries of tendons are the most common orthopedic injuries in athletic subjects, be they equine or human. When the tendon is suddenly damaged, an acute inflammatory phase occurs whereas its repetitive overloading may cause chronic injuries. Currently the criteria used for grading injuries are general and subjective, and therefore a reliable grading method would be an improvement. The main purpose of this study was to assess qualitatively the histological pattern of Masson trichrome stain in healthy and injured tendons; indeed, the known "paradox" of Masson staining was used to create an evaluation for the matrix of tendons, following experimental lesions and natural repair processes. A statistically significant difference of aniline-staining between healthy and lesioned tendons was observed. Overall, we think that the Masson staining might be regarded as an informative tool in discerning the collagen spatial arrangement and therefore the histological characteristics of tendons.

  4. The Effect of Sodium Hyaluronate on Ligamentation and Biomechanical Property of Tendon in Repair of Achilles Tendon Defect with Polyethylene Terephthalate Artificial Ligament: A Rabbit Tendon Repair Model

    Directory of Open Access Journals (Sweden)

    Shengkun Li

    2016-01-01

    Full Text Available The Achilles tendon is the most common ruptured tendon of human body. Reconstruction with polyethylene terephthalate (PET artificial ligament is recommended in some serious cases. Sodium hyaluronate (HA is beneficial for the healing of tendon injuries. We aimed to determine the effect of sodium hyaluronate in repair of Achilles tendon defect with PET artificial ligament in an animal tendon repair model. Sixteen New Zealand White rabbits were divided into two groups. Eight rabbits repaired with PET were assigned to PET group; the other eight rabbits repaired with PET along with injection of HE were assigned to HA-PET group. All rabbits were sacrificed at 4 and 8 weeks postoperatively for biomechanical and histological examination. The HA-PET group revealed higher biomechanical property compared with the PET group. Histologically, more collagen tissues grew into the HA-PET group compared with PET group. In conclusion, application of sodium hyaluronate can improve the healing of Achilles tendon reconstruction with polyethylene terephthalate artificial ligament.

  5. A leucine-rich diet and exercise affect the biomechanical characteristics of the digital flexor tendon in rats after nutritional recovery.

    Science.gov (United States)

    Barbosa, Alexandre Wesley Carvalho; Benevides, Gustavo Pereira; Alferes, Leda Maria Totti; Salomão, Emilianne Miguel; Gomes-Marcondes, Maria Cristina Cintra; Gomes, Laurecir

    2012-01-01

    An increase in the capacity of athletic performance depends on adequate nutrition, which ensures optimal function of the musculoskeletal system, including tendon stability. However, little is known about the status of tendons and extracellular matrix modifications during malnutrition and nutritional recovery when leucine is used in response to exercise conditioning. The purpose of this study was to evaluate the collagen content and biomechanical aspects of the deep digital flexor tendon (DDFT) in malnourished rats submitted to nutritional recovery (control diet or leucine-rich diet) and aerobic physical activity. After 60 days of undernourishment (6% protein diet), the malnourished rats were subsequently nutritionally recovered with a control diet or leucine-rich diet and trained or not (swimming, without overload) for 5 weeks. The biomechanical analysis and quantification of hydroxyproline were assessed in the DDFT in all experimental groups. The leucine-rich diet increased hydroxyproline content in the tension region, independently of the training. In the compression region, hydroxyproline content was higher in the malnourished and leucine-trained groups. Biomechanical analysis showed a lower load in the malnourished and all-trained groups. The lowest stress was observed with control-trained animals. The nutritional-recovered groups showed higher strain values corresponding to control group, while the lowest values were observed in malnourished and trained groups. The results suggest that a leucine-rich diet stimulates collagen synthesis of the DDFT, especially when in combination with physical exercise, and seems to determine the increase of resistance and the biomechanical characteristics of tendons.

  6. The Physiological Mechanisms of Effect of Vitamins and Amino Acids on Tendon and Muscle Healing: A Systematic Review.

    Science.gov (United States)

    Tack, Christopher; Shorthouse, Faye; Kass, Lindsy

    2017-11-15

    To evaluate current literature via systematic review to ascertain whether amino acids/ vitamins provide any influence on musculotendinous healing, and by which physiological mechanisms Methods: EBSCO, PUBMED, Science Direct, Embase Classic/ Embase, and MEDLINE were searched using terms including "vitamins", "amino acids", "healing", "muscle" and "tendon". The primary search had 479 citations, 466 of which were excluded predominantly due to non-randomised design. Randomised human and animal studies investigating all supplement types/ forms of administration were included. Critical appraisal of internal validity was assessed using the Cochrane risk of bias tool or the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool for human and animal studies, respectively. 2 reviewers performed duel data extraction. Twelve studies met criteria for inclusion: 8 examined tendon healing, 4 examined muscle healing. All studies used animal models, except 2 human trials using a combined integrator. Narrative synthesis was performed via content analysis of demonstrated statistically significant effects, and thematic analysis of proposed physiological mechanisms of intervention. Vitamin C/ taurine demonstrated indirect effects on tendon healing through anti-oxidant activity. Vitamin A/ glycine showed direct effects on extra-cellular matrix tissue synthesis. Vitamin E shows an anti-proliferative influence on collagen deposition. Leucine directly influences signalling pathways to promote muscle protein synthesis. Preliminary evidence exists demonstrating vitamins and amino acids may facilitate multi-level changes in musculotendinous healing; however recommendations on clinical utility should be made with caution. All animal studies and one human study show high risk of bias with moderate inter-observer agreement (k=0.46). Currently, there is limited evidence to support the use of vitamins and amino acids for musculotendinous injury. Both high quality

  7. Do Dietary Factors Influence Tendon Metabolism?

    Science.gov (United States)

    Scott, Alex; Nordin, Cara

    There is very little direct research to conclusively prove the relevance of diet in primary tendinopathies, however it seems prudent to ask whether our current knowledge about the impact of nutrition on collagen metabolism could be useful in assessing, preventing, or treating tendinopathy. The objective of this chapter is to discuss the potential impact (negative or positive) that nutrition may have on the metabolism of tendons by summarizing the related research. The chapter briefly discusses the roles that specific vitamins, amino acids, lipids, and antioxidants have in various processes of the body that may be directly or indirectly related to tenocyte metabolism.

  8. Tendon Gradient Mineralization for Tendon to Bone Interface Integration

    Science.gov (United States)

    Qu, Jin; Thoreson, Andrew R.; Chen, Qingshan; An, Kai-Nan; Amadio, Peter C.; Zhao, Chunfeng

    2014-01-01

    Tendon-to-bone integration is a great challenge for tendon or ligament reconstruction regardless of use of autograft or allograft tendons. We mineralized the tendon, thus transforming the tendon-to-bone into a “bone-to-bone” interface for healing. Sixty dog flexor digitorum profundus (FDP) tendons were divided randomly into 5 groups: 1) normal FDP tendon, 2) CaP (Non-extraction and mineralization without fetuin), 3) CaPEXT (Extraction by Na2HPO4 and mineralization without fetuin), 4) CaPFetuin (Non-extraction and mineralization with fetuin), and 5) CaPEXTFetuin (Extraction and mineralization with fetuin). The calcium and phosphate content significantly increased in tendons treated with combination of extraction and fetuin compared to the other treatments. Histology also revealed a dense mineral deposition throughout the tendon outer layers and penetrated into the tendon to a depth of 200 μm in a graded manner. Compressive moduli were significantly lower in the four mineralized groups compared with normal control group. No significant differences in maximum failure strength or stiffness were found in the suture pull-out test among all groups. Mineralization of tendon alters the interface from tendon to bone into mineralized tendon to bone, which may facilitate tendon-to-bone junction healing following tendon or ligament reconstruction. PMID:23939935

  9. Effects of adeno-associated virus (AAV) of transforming growth factors beta1 and beta3 (TGFbeta1,3) on promoting synthesis of glycosaminoglycan and collagen type II of dedifferentiated nucleus pulposus (NP) cells.

    Science.gov (United States)

    Sai, JiaMing; Hu, YouGu; Wang, DeChun

    2007-10-01

    The effects of AAV-TGFbeta(1) and AAV-TGFbeta(3) on promoting synthesis of glycosaminoglycan and collagen type II of dedifferentiated rabbit lumbar disc NP cells were studied in this work. The rabbit lumbar disc NP cells were isolated and cultured. The earlier and later dedifferentiated NP cells were established by subculture. The AAV transfection efficiency to dedifferentiated NP cells was analyzed with AAV-EGFP in vitro. After dedifferentiated NP cells were transfected by AAV-TGFbeta(1) or AAV-TGFbeta(3), their biological effects on promoting synthesis of glycosaminoglycan or collagen type II were detected and compared by the methods of (35)S incorporation or immunoblotting. The experimental results showed that AAV could transfect efficiently the earlier dedifferentiated NP cells, but its transfection rate was shown to be at a low level to the later dedifferentiated NP cells. Both AAV-TGFbeta(1) and AAV-TGFbeta(3) could promote the earlier dedifferentiated NP cells to synthesize glycosaminoglycan and collagen type II, and the effect of AAV-TGFbeta(1) was better than that of AAV-TGFbeta(3). For the later dedifferentiated NP cells, the AAV-TGFbeta(3) could promote their synthesis, but AAV-TGFbeta(1) could slightly inhibit their synthesis. Therefore, AAV-TGFbeta(1) and AAV-TGFbeta(3) could be used for the earlier dedifferentiated NP cells, and the TGFbeta(3) could be used as the objective gene for the later dedifferentiated NP cells.

  10. Peroneal tendon disorders.

    Science.gov (United States)

    Davda, Kinner; Malhotra, Karan; O'Donnell, Paul; Singh, Dishan; Cullen, Nicholas

    2017-06-01

    Pathological abnormality of the peroneal tendons is an under-appreciated source of lateral hindfoot pain and dysfunction that can be difficult to distinguish from lateral ankle ligament injuries.Enclosed within the lateral compartment of the leg, the peroneal tendons are the primary evertors of the foot and function as lateral ankle stabilisers.Pathology of the tendons falls into three broad categories: tendinitis and tenosynovitis, tendon subluxation and dislocation, and tendon splits and tears. These can be associated with ankle instability, hindfoot deformity and anomalous anatomy such as a low lying peroneus brevis or peroneus quartus.A thorough clinical examination should include an assessment of foot type (cavus or planovalgus), palpation of the peronei in the retromalleolar groove on resisted ankle dorsiflexion and eversion as well as testing of lateral ankle ligaments.Imaging including radiographs, ultrasound and MRI will help determine the diagnosis. Treatment recommendations for these disorders are primarily based on case series and expert opinion.The aim of this review is to summarise the current understanding of the anatomy and diagnostic evaluation of the peroneal tendons, and to present both conservative and operative management options of peroneal tendon lesions. Cite this article: EFORT Open Rev 2017;2:281-292. DOI: 10.1302/2058-5241.2.160047.

  11. Tendinopathy of the long head of the biceps tendon: histopathologic analysis of the extra-articular biceps tendon and tenosynovium.

    Science.gov (United States)

    Streit, Jonathan J; Shishani, Yousef; Rodgers, Mark; Gobezie, Reuben

    2015-01-01

    Bicipital tendinitis is a common cause of anterior shoulder pain, but there is no evidence that acute inflammation of the extra-articular long head of the biceps (LHB) tendon is the root cause of this condition. We evaluated the histologic findings of the extra-articular portion of the LHB tendon and synovial sheath in order to compare those findings to known histologic changes seen in other tendinopathies. Twenty-six consecutive patients (mean age 45.4±13.7 years) underwent an open subpectoral biceps tenodesis for anterior shoulder pain localized to the bicipital groove. Excised tendons were sent for histologic analysis. Specimens were graded using a semiquantitative scoring system to evaluate tenocyte morphology, the presence of ground substance, collagen bundle characteristics, and vascular changes. Chronic inflammation was noted in only two of 26 specimens, and no specimen demonstrated acute inflammation. Tenocyte enlargement and proliferation, characterized by increased roundness and size of the cell and nucleus with proteoglycan matrix expansion and myxoid degenerative changes, was found in all 26 specimens. Abundant ground substance, collagen bundle changes, and increased vascularization were visualized in all samples. Anterior shoulder pain attributed to the biceps tendon does not appear to be due to an inflammatory process in most cases. The histologic findings of the extra-articular portion of the LHB tendon and synovial sheath are similar to the pathologic findings in de Quervain tenosynovitis at the wrist, and may be due to a chronic degenerative process similar to this and other tendinopathies of the body.

  12. Collagen fiber with surface-grafted polyphenol as a novel support for Pd(0) nanoparticles: Synthesis, characterization and catalytic application

    Energy Technology Data Exchange (ETDEWEB)

    Wu Hao [Department of Biomass Chemistry and Engineering, Sichuan University, Chengdu 610065 (China); Wu Chao [National Engineering Laboratory for Clean Technology of Leather Manufacture, Sichuan University, Chengdu 610065 (China); He Qiang [Department of Biomass Chemistry and Engineering, Sichuan University, Chengdu 610065 (China); Liao Xuepin, E-mail: sibitannin@vip.163.com [National Engineering Laboratory for Clean Technology of Leather Manufacture, Sichuan University, Chengdu 610065 (China); Shi Bi, E-mail: xpliao@scu.edu.cn [Department of Biomass Chemistry and Engineering, Sichuan University, Chengdu 610065 (China); National Engineering Laboratory for Clean Technology of Leather Manufacture, Sichuan University, Chengdu 610065 (China)

    2010-06-15

    The aim of this study is to use collagen fiber (CF) as a natural polymeric support to synthesize a novel palladium (Pd) nanoparticle catalyst. To achieve a stable immobilization of Pd on CF support, epigallocatechin-3-gallate (EGCG), a typical plant polyphenol, was grafted onto CF surface, acting both as dispersing and stabilizing agent for Pd nanoparticles. Scanning electron microscopy showed that this catalyst was in ordered fibrous state with high flexibility. The presence of EGCG grafted on CF and the interaction mechanism of Pd ions with support was investigated by X-ray photoelectron spectroscopy. X-ray diffraction and transmission electron microscopy offered evidence that the well-dispersed Pd nanoparticles were generated on the outer surface of CF. By using the hydrogenation of allyl alcohol as a model reaction, the synthesized catalyst presented remarkably improved activity, selectivity and reusability as compared with the Pd catalyst supported by CF without grafting of EGCG.

  13. Stabilization and anomalous hydration of collagen fibril under heating.

    Directory of Open Access Journals (Sweden)

    Sasun G Gevorkian

    Full Text Available BACKGROUND: Type I collagen is the most common protein among higher vertebrates. It forms the basis of fibrous connective tissues (tendon, chord, skin, bones and ensures mechanical stability and strength of these tissues. It is known, however, that separate triple-helical collagen macromolecules are unstable at physiological temperatures. We want to understand the mechanism of collagen stability at the intermolecular level. To this end, we study the collagen fibril, an intermediate level in the collagen hierarchy between triple-helical macromolecule and tendon. METHODOLOGY/PRINCIPAL FINDING: When heating a native fibril sample, its Young's modulus decreases in temperature range 20-58°C due to partial denaturation of triple-helices, but it is approximately constant at 58-75°C, because of stabilization by inter-molecular interactions. The stabilization temperature range 58-75°C has two further important features: here the fibril absorbs water under heating and the internal friction displays a peak. We relate these experimental findings to restructuring of collagen triple-helices in fibril. A theoretical description of the experimental results is provided via a generalization of the standard Zimm-Bragg model for the helix-coil transition. It takes into account intermolecular interactions of collagen triple-helices in fibril and describes water adsorption via the Langmuir mechanism. CONCLUSION/SIGNIFICANCE: We uncovered an inter-molecular mechanism that stabilizes the fibril made of unstable collagen macromolecules. This mechanism can be relevant for explaining stability of collagen.

  14. Human Achilles tendon glycation and function in diabetes

    DEFF Research Database (Denmark)

    Couppe, Christian; Svensson, Rene Brüggebusch; Kongsgaard, Mads

    2016-01-01

    Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between...... tissue cross-linking were greater in diabetic patients compared to controls. The higher foot pressure indicates that material stiffness of tendon and other tissue (e.g skin and joint capsule) may influence on foot gait. The difference in foot pressure distribution may contribute to the development...... of foot ulcers in diabetic patients....

  15. Effect of Calendula officinalis cream on achilles tendon healing.

    Science.gov (United States)

    Aro, A A; Perez, M O; Vieira, C P; Esquisatto, M A M; Rodrigues, R A F; Gomes, L; Pimentel, E R

    2015-02-01

    In recent years, the scientific community has undertaken research on plant extracts, searching for compounds with pharmacological activities that can be used in diverse fields of medicine. Calendula officinalis L. is known to have antioxidant, anti-inflammatory, antibacterial, and wound healing properties when used to treat skin burns. Therefore, the purpose of this study was to analyze the effects of C. officinalis on the initial phase of Achilles tendon healing. Wistar rats were separated in three groups: Calendula (Cal)-rats with a transected tendon were treated with topical applications of C. officinalis cream and then euthanized 7 days after injury; Control (C)-rats were treated with only vehicle after transection; and Normal (N)-rats without tenotomy. Higher concentrations of hydroxyproline (an indicator of total collagen) and non-collagenous proteins were observed in the Cal group in relation to the C group. Zymography showed no difference in the amount of the isoforms of metalloproteinase-2 and of metalloproteinase-9, between C and Cal groups. Polarization microscopy images analysis showed that the Cal group presented a slightly higher birefringence compared with the C group. In sections of tendons stained with toluidine blue, the transected groups presented higher metachromasy as compared with the N group. Immunocytochemistry analysis for chondroitin-6-sulfate showed no difference between the C and Cal groups. In conclusion, the topical application of C. officinalis after tendon transection increases the concentrations of collagen and non-collagenous proteins, as well as the collagen organization in the initial phase of healing. © 2014 Wiley Periodicals, Inc.

  16. Alginate-Collagen Fibril Composite Hydrogel

    Directory of Open Access Journals (Sweden)

    Mahmoud Baniasadi

    2015-02-01

    Full Text Available We report on the synthesis and the mechanical characterization of an alginate-collagen fibril composite hydrogel. Native type I collagen fibrils were used to synthesize the fibrous composite hydrogel. We characterized the mechanical properties of the fabricated fibrous hydrogel using tensile testing; rheometry and atomic force microscope (AFM-based nanoindentation experiments. The results show that addition of type I collagen fibrils improves the rheological and indentation properties of the hydrogel.

  17. Adequacy of palmaris longus and plantaris tendons for tendon grafting.

    Science.gov (United States)

    Jakubietz, Michael G; Jakubietz, Danni F; Gruenert, Joerg G; Zahn, Robert; Meffert, Rainer H; Jakubietz, Rafael G

    2011-04-01

    The reconstruction of tendon defects is challenging. The palmaris longus and plantaris tendon are generally considered best for tendon grafting. Only a few studies have examined whether these tendons, when present, meet criteria for successful grafting. The purpose of this study was to evaluate these tendons in regard to adequacy as tendon grafts. To evaluate adequacy for grafting, the palmaris longus and plantaris tendons were harvested from 92 arms and legs of 46 cadavers. Macroscopic evaluation and measurements concerning presence, length, and diameter of the tendons were obtained. Criteria for adequacy were a minimum length of 15 cm with diameter of 3 mm or, alternatively, 30 cm with a diameter of 1.5 mm. The palmaris longus tendon was present bilaterally in 36 cases and was absent bilaterally in 4 cases. The plantaris tendon was present bilaterally in 38 cases and absent bilaterally in 4 cases. In 29 cadavers, the palmaris longus tendon did not meet the criteria to be used as a tendon graft. Only in 8 cases were the tendons satisfactory for grafting bilaterally. The plantaris tendon met criteria for grafting in 20 cases bilaterally. In 17 cases, the tendons were considered inadequate bilaterally. Despite their presence, the palmaris longus and plantaris tendons are adequate for grafting less often than previously thought. In less than 50%, the tendons, although present, would serve as useful grafts. Our findings underscore the importance of choosing a second donor site before surgery in case the primarily selected tendon is not found to be suitable. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  18. Tendon Transfers for Tetraplegia.

    Science.gov (United States)

    Bednar, Michael S

    2016-08-01

    It is estimated that 65% to 75% of patients with cervical spinal cord injuries could benefit from upper extremity tendon transfer surgery. The goals of surgery are to restore elbow extension, as well as hand pinch, grasp, and release. Patients who have defined goals, actively participate in therapy, and understand expected outcomes, appear to have the highest satisfaction following tendon transfer procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. COLLAGEN DRESSING: A PROSPECTIVE RANDOMIZED TRIAL OF COLLAGEN SHEET AS A BIOLOGICAL DRESSING AND ITS ROLE IN THE CHRONIC NON-HEALING WOUNDS

    OpenAIRE

    M. Ramula; J. Joyce Prabhakar; N. Lakshmipathy; Vaithiswaran Arikrishnan

    2016-01-01

    BACKGROUND Collagen is the most abundantly present connective tissue. In higher animals, primarily as extracellular insoluble fibres and the fibres account for large part of organic mass of skin, tendon, blood vessel, bone teeth, cornea and vitreous humour. Collagen also provides the framework of parenchymal organs and basement membrane. The collagens constitute a family of proteins selected during evolution for the execution of several (mainly structural) functions. During the...

  20. A Fibre-Reinforced Poroviscoelastic Model Accurately Describes the Biomechanical Behaviour of the Rat Achilles Tendon

    Science.gov (United States)

    Heuijerjans, Ashley; Matikainen, Marko K.; Julkunen, Petro; Eliasson, Pernilla; Aspenberg, Per; Isaksson, Hanna

    2015-01-01

    Background Computational models of Achilles tendons can help understanding how healthy tendons are affected by repetitive loading and how the different tissue constituents contribute to the tendon’s biomechanical response. However, available models of Achilles tendon are limited in their description of the hierarchical multi-structural composition of the tissue. This study hypothesised that a poroviscoelastic fibre-reinforced model, previously successful in capturing cartilage biomechanical behaviour, can depict the biomechanical behaviour of the rat Achilles tendon found experimentally. Materials and Methods We developed a new material model of the Achilles tendon, which considers the tendon’s main constituents namely: water, proteoglycan matrix and collagen fibres. A hyperelastic formulation of the proteoglycan matrix enabled computations of large deformations of the tendon, and collagen fibres were modelled as viscoelastic. Specimen-specific finite element models were created of 9 rat Achilles tendons from an animal experiment and simulations were carried out following a repetitive tensile loading protocol. The material model parameters were calibrated against data from the rats by minimising the root mean squared error (RMS) between experimental force data and model output. Results and Conclusions All specimen models were successfully fitted to experimental data with high accuracy (RMS 0.42-1.02). Additional simulations predicted more compliant and soft tendon behaviour at reduced strain-rates compared to higher strain-rates that produce a stiff and brittle tendon response. Stress-relaxation simulations exhibited strain-dependent stress-relaxation behaviour where larger strains produced slower relaxation rates compared to smaller strain levels. Our simulations showed that the collagen fibres in the Achilles tendon are the main load-bearing component during tensile loading, where the orientation of the collagen fibres plays an important role for the tendon

  1. Adaptation of bone and tendon to prolonged hindlimb suspension in rats

    Science.gov (United States)

    Vailas, Arthur C.; Deluna, Diane M.; Lewis, Lisa L.; Curwin, Sandra L.; Roy, Roland R.

    1988-01-01

    The effect of a sustained deprivation of ground reaction forces on mineralized and soft connective tissues was investigated in rats subjected to 28-d-long hind-limb suspension. The results of morphological and biochemical studies carried out on femurs and patellar tendons obtained from suspended and nonsuspended 110-d-old rats showed that prolonged suspension led to an increase of the minimum diameter of the femur middiaphysis (by 12 percent), without any significant alterations in cortical area, density, mineral and collagen concentrations, femur wet weight, length, and DNA and uronic acid concentrations. However, in the patellar tendons of suspended rats, the collagen and proteoglycan concentrations were 28 percent lower than in tendons obtained from nonsuspended animals. These results suggest that ground reaction forces are important for the maintenance of cortical bone and patellar tendon homeostasis during weight-bearing conditions.

  2. In vivo effects of ELF MFs on collagen synthesis, free radical processes, natural antioxidant system, respiratory burst system, immune system activities, and electrolytes in the skin, plasma, spleen, lung, kidney, and brain tissues.

    Science.gov (United States)

    Seyhan, Nesrin; Canseven, Ayse Gulnihal

    2006-01-01

    In this study, the results related with the effects of 50 Hz, 0.2 mT-3 mT MFs exposures on collagen synthesis, epilepsy, electrolytes, lipid peroxidation (MDA), Nitric Oxide (NOx), respiratory burst system (MPO), antioxidant defense system (GSH), and immune system (NK cell activity) in spleen, skin, lung, kidney, brain, and plasma tissues performed at Gazi Biophysics Department are reviewed. Our studies indicate that ELF MFs had effects on the tissues examined.

  3. Upregulation of Bone Morphogenetic Protein-2 Synthesis and Consequent Collagen II Expression in Leptin-stimulated Human Chondrocytes.

    Science.gov (United States)

    Chang, Shun-Fu; Hsieh, Rong-Ze; Huang, Kuo-Chin; Chang, Cheng Allen; Chiu, Fang-Yao; Kuo, Hsing-Chun; Chen, Cheng-Nan; Su, Yu-Ping

    2015-01-01

    Bone morphogenetic proteins (BMPs) play positive roles in cartilage development, but they can barely be detected in healthy articular cartilage. However, recent evidence has indicated that BMPs could be detected in osteoarthritic and damaged cartilage and their precise roles have not been well defined. Extremely high amounts of leptin have been reported in obese individuals, which can be associated with osteoarthritis (OA) development. The aim of this study was to investigate whether BMPs could be induced in human primary chondrocytes during leptin-stimulated OA development and the underlying mechanism. We found that expression of BMP-2 mRNA, but not BMP-4, BMP-6, or BMP-7 mRNA, could be increased in human primary chondrocytes under leptin stimulation. Moreover, this BMP-2 induction was mediated through transcription factor-signal transducer and activator of transcription (STAT) 3 activation via JAK2-ERK1/2-induced Ser727-phosphorylation. Of note, histone deacetylases (HDACs) 3 and 4 were both involved in modulating leptin-induced BMP-2 mRNA expression through different pathways: HDAC3, but not HDAC4, associated with STAT3 to form a complex. Our results further demonstrated that the role of BMP-2 induction under leptin stimulation is to increase collagen II expression. The findings in this study provide new insights into the regulatory mechanism of BMP-2 induction in leptin-stimulated chondrocytes and suggest that BMP-2 may play a reparative role in regulating leptin-induced OA development.

  4. Upregulation of Bone Morphogenetic Protein-2 Synthesis and Consequent Collagen II Expression in Leptin-stimulated Human Chondrocytes.

    Directory of Open Access Journals (Sweden)

    Shun-Fu Chang

    Full Text Available Bone morphogenetic proteins (BMPs play positive roles in cartilage development, but they can barely be detected in healthy articular cartilage. However, recent evidence has indicated that BMPs could be detected in osteoarthritic and damaged cartilage and their precise roles have not been well defined. Extremely high amounts of leptin have been reported in obese individuals, which can be associated with osteoarthritis (OA development. The aim of this study was to investigate whether BMPs could be induced in human primary chondrocytes during leptin-stimulated OA development and the underlying mechanism. We found that expression of BMP-2 mRNA, but not BMP-4, BMP-6, or BMP-7 mRNA, could be increased in human primary chondrocytes under leptin stimulation. Moreover, this BMP-2 induction was mediated through transcription factor-signal transducer and activator of transcription (STAT 3 activation via JAK2-ERK1/2-induced Ser727-phosphorylation. Of note, histone deacetylases (HDACs 3 and 4 were both involved in modulating leptin-induced BMP-2 mRNA expression through different pathways: HDAC3, but not HDAC4, associated with STAT3 to form a complex. Our results further demonstrated that the role of BMP-2 induction under leptin stimulation is to increase collagen II expression. The findings in this study provide new insights into the regulatory mechanism of BMP-2 induction in leptin-stimulated chondrocytes and suggest that BMP-2 may play a reparative role in regulating leptin-induced OA development.

  5. Collagenous gastritis.

    Science.gov (United States)

    Jin, Xiaoyi; Koike, Tomoyuki; Chiba, Takashi; Kondo, Yutaka; Ara, Nobuyuki; Uno, Kaname; Asano, Naoki; Iijima, Katsunori; Imatani, Akira; Watanabe, Mika; Shirane, Akio; Shimosegawa, Tooru

    2013-09-01

    In the present paper, we report a case of rare collagenous gastritis. The patient was a 25-year-old man who had experienced nausea, abdominal distention and epigastralgia since 2005. Esophagogastroduodenoscopy (EGD) carried out at initial examination by the patient's local doctor revealed an extensively discolored depression from the upper gastric body to the lower gastric body, mainly including the greater curvature, accompanied by residual mucosa with multiple islands and nodularity with a cobblestone appearance. Initial biopsies sampled from the nodules and accompanying atrophic mucosa were diagnosed as chronic gastritis. In August, 2011, the patient was referred to Tohoku University Hospital for observation and treatment. EGD at our hospital showed the same findings as those by the patient's local doctor. Pathological findings included a membranous collagen band in the superficial layer area of the gastric mucosa, which led to a diagnosis of collagenous gastritis. Collagenous gastritis is an extremely rare disease, but it is important to recognize its characteristic endoscopic findings to make a diagnosis. © 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.

  6. Influence of acute and chronic streptozotocin-induced diabetes on the rat tendon extracellular matrix and mechanical properties

    DEFF Research Database (Denmark)

    Volper, Brent D; Huynh, Richard T; Arthur, Kathryn A

    2015-01-01

    Diabetes is a major risk factor for tendinopathy, and tendon abnormalities are common in diabetic patients. The purpose of the present study was to evaluate the effect of streptozotocin (60 mg/kg)-induced diabetes and insulin therapy on tendon mechanical and cellular properties. Sprague-Dawley rats...... (n = 40) were divided into the following four groups: nondiabetic (control), 1 wk of diabetes (acute), 10 wk of diabetes (chronic), and 10 wk of diabetes with insulin treatment (insulin). After 10 wk, Achilles tendon and tail fascicle mechanical properties were similar between groups (P > 0.05). Cell.......05). In contrast, patellar tendon hydroxylysyl pyridinoline cross linking and collagen fibril organization were unchanged by diabetes or insulin (P > 0.05). Our findings suggest that 10 wk of streptozotocin-induced diabetes does not alter rat tendon mechanical properties even with an increase in collagen content...

  7. Synthesis of α-collagen fragments and research of their influence on the degree of hydration of a model of epidermis.

    Science.gov (United States)

    Lubkowska, Beata; Grobelna, Beata; Maćkiewicz, Zbigniew

    2013-02-01

    In recent years the interest into areas of science, such as cosmetology, dermatology, pharmacology or aesthetic medicine has increased significantly. Scientists are more frequently looking for ingredients that affect the skin's condition and slow down the aging process. Practically every year, the scientists discover a number of new chemical substances (both natural and synthetic) that can be potentially used to manufacture cosmetics. To evaluate the influence of selected peptides derived from α-collagen fragments on the degree of hydration of a model of epidermis isolated from a pig. The synthesis of selected cosmetic oligopeptides were performed manually, on the solid medium, using procedure of SPPS (solid phase peptide synthesis). Following components: aqua, carbomer, glycerine, phenonip, D-panthenol, dimethicone and triethanolamine were used to prepare a reference hydrogel masks. Both the number of components and the composition of hydrogels have been developed individually for the purposes of this research. For this study the skin from a domestic pig was used. The degree of the skin hydration was measured with the SKINTEST plus camera, which uses the latest semiconductor technology. During the study the absorption of hydrogels with peptides was faster than that of the reference hydrogel mask. The combination of hydrophilic properties of the peptide with hydrophobic properties of Palm enabled receiving an amphiphilic structure. Such molecules are considered to be able to penetrate the corneum barrier with the greatest ease. The results showed that the modified compounds have contributed to water retention in the cells, thereby increasing the degree of hydration of the biological material.

  8. Detection of partial-thickness tears in ligaments and tendons by Stokes-polarimetry imaging

    Science.gov (United States)

    Kim, Jihoon; John, Raheel; Walsh, Joseph T.

    2008-02-01

    A Stokes polarimetry imaging (SPI) system utilizes an algorithm developed to construct degree of polarization (DoP) image maps from linearly polarized light illumination. Partial-thickness tears of turkey tendons were imaged by the SPI system in order to examine the feasibility of the system to detect partial-thickness rotator cuff tear or general tendon pathology. The rotating incident polarization angle (IPA) for the linearly polarized light provides a way to analyze different tissue types which may be sensitive to IPA variations. Degree of linear polarization (DoLP) images revealed collagen fiber structure, related to partial-thickness tears, better than standard intensity images. DoLP images also revealed structural changes in tears that are related to the tendon load. DoLP images with red-wavelength-filtered incident light may show tears and related organization of collagen fiber structure at a greater depth from the tendon surface. Degree of circular polarization (DoCP) images exhibited well the horizontal fiber orientation that is not parallel to the vertically aligned collagen fibers of the tendon. The SPI system's DOLP images reveal alterations in tendons and ligaments, which have a tissue matrix consisting largely of collagen, better than intensity images. All polarized images showed modulated intensity as the IPA was varied. The optimal detection of the partial-thickness tendon tears at a certain IPA was observed. The SPI system with varying IPA and spectral information can improve the detection of partial-thickness rotator cuff tears by higher visibility of fiber orientations and thereby improve diagnosis and treatment of tendon related injuries.

  9. Determination of markers for collagen type I turnover in peritendinous human tissue by microdialysis

    DEFF Research Database (Denmark)

    Olesen, J L; Langberg, Henning; Heinemeier, K M

    2006-01-01

    Previous results from our group have shown that loading of human tendon elevates tendinous type I collagen production measured by microdialysis. However, exclusion of the observed elevation as a response to trauma from inserting the microdialysis catheters or a possible influence from the collagen...

  10. History of flexor tendon repair.

    Science.gov (United States)

    Manske, Paul R

    2005-05-01

    The first issue of Hand Clinics published 20 years ago was devoted to flexor tendon injuries. This was most appropriate, because no subject in hand surgery has sparked more interest or discussion. That inaugural issue included excellent presentations on the basic science of tendon injuries (anatomy, biomechanics, nutrition, healing, adhesions) and the clinical practice of tendon repair. Of interest, there was no presentation on the fascinating history of flexor tendon surgery. It is most appropriate, therefore, that this current update of the flexor tendon begins with a historical review of the evolution of flexor tendon repair.

  11. Focal experimental injury leads to widespread gene expression and histologic changes in equine flexor tendons.

    Directory of Open Access Journals (Sweden)

    Else Jacobson

    Full Text Available It is not known how extensively a localised flexor tendon injury affects the entire tendon. This study examined the extent of and relationship between histopathologic and gene expression changes in equine superficial digital flexor tendon after a surgical injury. One forelimb tendon was hemi-transected in six horses, and in three other horses, one tendon underwent a sham operation. After euthanasia at six weeks, transected and control (sham and non-operated contralateral tendons were regionally sampled (medial and lateral halves each divided into six 3 cm regions for histologic (scoring and immunohistochemistry and gene expression (real time PCR analysis of extracellular matrix changes. The histopathology score was significantly higher in transected tendons compared to control tendons in all regions except for the most distal (P ≤ 0.03 with no differences between overstressed (medial and stress-deprived (lateral tendon halves. Proteoglycan scores were increased by transection in all but the most proximal region (P < 0.02, with increased immunostaining for aggrecan, biglycan and versican. After correcting for location within the tendon, gene expression for aggrecan, versican, biglycan, lumican, collagen types I, II and III, MMP14 and TIMP1 was increased in transected tendons compared with control tendons (P < 0.02 and decreased for ADAMTS4, MMP3 and TIMP3 (P < 0.001. Aggrecan, biglycan, fibromodulin, and collagen types I and III expression positively correlated with all histopathology scores (P < 0.001, whereas lumican, ADAMTS4 and MMP14 expression positively correlated only with collagen fiber malalignment (P < 0.001. In summary, histologic and associated gene expression changes were significant and widespread six weeks after injury to the equine SDFT, suggesting rapid and active development of tendinopathy throughout the entire length of the tendon. These extensive changes distant to the focal injury may contribute to poor functional outcomes

  12. Tendon transfer or tendon graft for ruptured finger extensor tendons in rheumatoid hands.

    Science.gov (United States)

    Chung, U S; Kim, J H; Seo, W S; Lee, K H

    2010-05-01

    We evaluated the clinical outcome of tendon reconstruction using tendon graft or tendon transfer and the parameters related to clinical outcome in 51 wrists of 46 patients with rheumatoid arthritis with finger extensor tendon ruptures. At a mean follow-up of 5.6 years, the mean metacarpophalangeal (MP) joint extension lag was 8 degrees (range, 0-45) and the mean visual analogue satisfaction scale was 74 (range, 10-100). Clinical outcome did not differ significantly between tendon grafting and tendon transfer. The MP joint extension lag correlated with the patient's satisfaction score, but the pulp-to-palm distance did not correlate with patient satisfaction. We conclude that both tendon grafting and tendon transfer are reliable reconstruction methods for ruptured finger extensor tendons in rheumatoid hands.

  13. Mesenchymal stem cells modulate release of matrix proteins from tendon surfaces in vitro: a potential beneficial therapeutic effect.

    Science.gov (United States)

    Garvican, Elaine R; Dudhia, Jayesh; Alves, Ana-Liz; Clements, Lucy E; Plessis, Francois Du; Smith, Roger K W

    2014-05-01

    Injury of tendons contained within a synovial environment, such as joint, bursa or tendon sheath, frequently fails to heal and releases matrix proteins into the synovial fluid, driving inflammation. This study investigated the effectiveness of cells to seal tendon surfaces and provoke matrix synthesis as a possible effective injectable therapy. Equine flexor tendon explants were cultured overnight in suspensions of bone marrow and synovium-derived mesenchymal stems cells and, as controls, two sources of fibroblasts, derived from tendon and skin, which adhered to the explants. Release of the most abundant tendon extracellular matrix proteins into the media was assayed, along with specific matrix proteins synthesis by real-time PCR. Release of extracellular matrix proteins was influenced by the coating cell type. Fibroblasts from skin and tendon appeared less capable of preventing the release of matrix proteins than mesenchymal stems cells. The source of cell is an important consideration for cell therapy.

  14. Camel milk attenuates the biochemical and morphological features of diabetic nephropathy: inhibition of Smad1 and collagen type IV synthesis.

    Science.gov (United States)

    Korish, Aida A; Abdel Gader, Abdel Galil; Korashy, Hesham M; Al-Drees, Abdul Majeed; Alhaider, Abdulqader A; Arafah, Maha M

    2015-03-05

    Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM) that worsens its morbidity and mortality. There is evidence that camel milk (CM) improves the glycemic control in DM but its effect on the renal complications especially the DN remains unclear. Thus the current study aimed to characterize the effects of CM treatment on streptozotocin (STZ)-induced DN. Using STZ-induced diabetes, we investigated the effect of CM treatment on kidney function, proteinuria, renal Smad1, collagen type IV (Col4), blood glucose, insulin resistance (IR), lipid peroxidation, the antioxidant superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH). In addition renal morphology was also examined. The current results showed that rats with untreated diabetes exhibited marked hyperglycemia, IR, high serum urea and creatinine levels, excessive proteinuria, increased renal Smad1 and Col4, glomerular expansion, and extracellular matrix deposition. There was also increased lipid peroxidation products, decreased antioxidant enzyme activity and GSH levels. Camel milk treatment decreased blood glucose, IR, and lipid peroxidation. Superoxide dismutase and CAT expression, CAT activity, and GSH levels were increased. The renoprotective effects of CM were demonstrated by the decreased serum urea and creatinine, proteinuria, Smad1, Col4, and preserved normal tubulo-glomerular morphology. In conclusion, beside its hypoglycemic action, CM attenuates the early changes of DN, decreased renal Smad1 and Col4. This could be attributed to a primary action on the glomerular mesangial cells, or secondarily to the hypoglycemic and antioxidant effects of CM. The protective effects of CM against DN support its use as an adjuvant anti-diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study

    Directory of Open Access Journals (Sweden)

    Weinans Harrie

    2007-02-01

    Full Text Available Abstract Background Tendinosis lesions show an increase of glycosaminoglycan amount, calcifications, and lipid accumulation. Therefore, altered cellular differentiation might play a role in the etiology of tendinosis. This study investigates whether adolescent human tendon tissue contains a population of cells with intrinsic differentiation potential. Methods Cells derived from adolescent non-degenerative hamstring tendons were characterized by immunohistochemistry and FACS-analysis. Cells were cultured for 21 days in osteogenic, adipogenic, and chondrogenic medium and phenotypical evaluation was carried out by immunohistochemical and qPCR analysis. The results were compared with the results of similar experiments on adult bone marrow-derived stromal cells (BMSCs. Results Tendon-derived cells stained D7-FIB (fibroblast-marker positive, but α-SMA (marker for smooth muscle cells and pericytes negative. Tendon-derived cells were 99% negative for CD34 (endothelial cell marker, and 73% positive for CD105 (mesenchymal progenitor-cell marker. In adipogenic medium, intracellular lipid vacuoles were visible and tendon-derived fibroblasts showed upregulation of adipogenic markers FABP4 (fatty-acid binding protein 4 and PPARG (peroxisome proliferative activated receptor γ. In chondrogenic medium, some cells stained positive for collagen 2 and tendon-derived fibroblasts showed upregulation of collagen 2 and collagen 10. In osteogenic medium Von Kossa staining showed calcium deposition although osteogenic markers remained unaltered. Tendon-derived cells and BMCSs behaved largely comparable, although some distinct differences were present between the two cell populations. Conclusion This study suggests that our population of explanted human tendon cells has an intrinsic differentiation potential. These results support the hypothesis that there might be a role for altered tendon-cell differentiation in the pathophysiology of tendinosis.

  16. Tendon-derived progenitor cells improve healing of collagenase-induced flexor tendinitis.

    Science.gov (United States)

    Durgam, Sushmitha S; Stewart, Allison A; Sivaguru, Mayandi; Wagoner Johnson, Amy J; Stewart, Matthew C

    2016-12-01

    Tendinitis is a common and a performance-limiting injury in athletes. This study describes the value of intralesional tendon-derived progenitor cell (TDPC) injections in equine flexor tendinitis. Collagenase-induced tendinitis was created in both front superficial digital flexor (SDF) tendons. Four weeks later, the forelimb tendon lesions were treated with 1 × 107 autogenous TDPCs or saline. Tendinitis was also induced by collagenase in one hind SDF tendon, to study the survival and distribution of DiI-labeled TDPCs 1, 2, 4, and 6 weeks after injection. The remaining normal tendon was used as a "control." Twelve weeks after forelimb TDPC injections, tendons were harvested for assessment of matrix gene expression, biochemical, biomechanical, and histological characteristics. DiI-labeled TDPCs were abundant 1 week after injection but gradually declined over time and were undetectable after 6 weeks. Twelve weeks after TDPC injection, collagens I and III, COMP and tenomodulin mRNA levels were similar (p = 0.3) in both TDPC and saline groups and higher (p < 0.05) than normal tendon. Yield and maximal stresses of the TDPC group were significantly greater (p = 0.005) than the saline group's and similar (p = 0.6) to normal tendon. However, the elastic modulus of the TDPC and saline groups were not significantly different (p = 0.32). Histological assessment of the repair tissues with Fourier transform-second harmonic generation imaging demonstrated that collagen alignment was significantly better (p = 0.02) in TDPC group than in the saline controls. In summary, treating collagenase-induced flexor tendon lesions with TDPCs improved the tensile strength and collagen fiber alignment of the repair tissue. Study Design © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2162-2171, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. [Achilles tendon rupture].

    Science.gov (United States)

    Thermann, H; Hüfner, T; Tscherne, H

    2000-03-01

    The treatment of acute of Achilles tendon rupture experienced a dynamic development in the last ten years. Decisive for this development was the application of MRI and above all the ultrasonography in the diagnostics of the pathological changes and injuries of tendons. The question of rupture morphology as well as different courses of healing could be now evaluated objectively. These advances led consequently to new modalities in treatment concepts and rehabilitation protocols. The decisive input for improvements of the outcome results and particularly the shortening of the rehabilitation period came with introduction of the early functional treatment in contrast to immobilizing plaster treatment. In a prospective randomized study (1987-1989) at the Trauma Dept. of the Hannover Medical School could show no statistical differences comparing functional non-operative with functional operative therapy with a special therapy boot (Variostabil/Adidas). The crucial criteria for therapy selection results from the sonographically measured position of the tendon stumps in plantar flexion (20 degrees). With complete adaptation of the tendons' ends surgical treatment does not achieve better results than non-operative functional treatment in term of tendon healing and functional outcome. Regarding the current therapeutic standards each method has is advantages and disadvantages. Both, the operative and non-operative functional treatment enable a stable tendon healing with a low risk of re-rupture (1-2%). Meanwhile there is consensus for early functional after-treatment of the operated Achilles' tendons. There seems to be a trend towards non-operative functional treatment in cases of adequate sonographical findings, or to minimal invasive surgical techniques.

  18. The effect of platelet-rich plasma on Achilles tendon healing in a rabbit model.

    Science.gov (United States)

    Takamura, Masaki; Yasuda, Toshito; Nakano, Atsushi; Shima, Hiroaki; Neo, Masashi

    2017-01-01

    The aim of the present study was to evaluate the effects of PRP on Achilles tendon healing in rabbits during the inflammatory, proliferative, and remodeling phases by histological examination and quantitative assessments. Fifty mature male Japanese albino rabbits with severed Achilles tendons were divided into two equal groups and treated with platelet-rich plasma (PRP) or left untreated. Tendon tissue was harvested at 1, 2, 3, 4, and 6 weeks after treatment, and sections were stained with hematoxylin-eosin and monoclonal antibodies against CD31 and type I collagen. Collagen fibers proliferated more densely early after severance, and subsequent remodeling of the collagen fibers and approximation of normal tendinous tissue occurred earlier in the PRP group than in the control group. The fibroblast number was significantly higher in the PRP group than in the control group at 1 and 2 weeks. Similarly, the area ratio of CD31-positive cells was significantly higher in the PRP group than in the control group at 1 and 2 weeks. Positive staining for type I collagen was more intense in the PRP group than in the control group after 3 weeks, indicating tendon maturation. Administration of PRP shortened the inflammatory phase and promoted tendon healing during the proliferative phase. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

  19. Patellar Tendon Rupture after Lateral Release without Predisposing Systemic Disease or Steroid Use

    Directory of Open Access Journals (Sweden)

    S. De Giorgi

    2015-01-01

    Full Text Available Arthroscopic technique for lateral release is the most widely used procedure for the correction of recurrent dislocations of the patella. In the relevant literature, several complications of lateral release are described, but the spontaneous patellar tendon rupture has never been suggested as a possible complication of this surgical procedure. Patellar tendon rupture is a rather infrequent and often unilateral lesion. Nevertheless, in case of systemic diseases (LES, rheumatoid arthritis, and chronic renal insufficiency that can weaken collagen structures, bilateral patellar tendon ruptures are described. We report a case of a 24-year-old girl with spontaneous rupture of patellar tendon who, at the age of 16, underwent an arthroscopic lateral release for recurrent dislocation of the patella. This is the first case of described spontaneous patellar tendon rupture that occurred some years after an arthroscopic lateral release.

  20. The collagen microfibil model as a tool for leather scientists

    Science.gov (United States)

    Collagen, a structural protein of the extracellular matrix, gives strength and form to the skin, tendons, bones, cornea and teeth of mammals. The discovery by early humans that the skin of an animal, slaughtered for meat, could be preserved by exposing it to smoke or rubbing with fat, led to the pr...

  1. Expression of type XXIII collagen mRNA and protein.

    Science.gov (United States)

    Koch, Manuel; Veit, Guido; Stricker, Sigmar; Bhatt, Pinaki; Kutsch, Stefanie; Zhou, Peihong; Reinders, Elina; Hahn, Rita A; Song, Rich; Burgeson, Robert E; Gerecke, Donald R; Mundlos, Stefan; Gordon, Marion K

    2006-07-28

    Collagen XXIII is a member of the transmembranous subfamily of collagens containing a cytoplasmic domain, a membrane-spanning hydrophobic domain, and three extracellular triple helical collagenous domains interspersed with non-collagenous domains. We cloned mouse, chicken, and humanalpha1(XXIII) collagen cDNAs and showed that this non-abundant collagen has a limited tissue distribution in non-tumor tissues. Lung, cornea, brain, skin, tendon, and kidney are the major sites of expression. In contrast, five transformed cell lines were tested for collagen XXIII expression, and all expressed the mRNA. In vivo the alpha1(XXIII) mRNA is found in mature and developing organs, the latter demonstrated using stages of embryonic chick cornea and mouse embryos. Polyclonal antibodies were generated in guinea pig and rabbit and showed that collagen XXIII has a transmembranous form and a shed form. Comparison of collagen XXIII with its closest relatives in the transmembranous subfamily of collagens, types XIII and XXV, which have the same number of triple helical and non-collagenous regions, showed that there is a discontinuity in the alignment of domains but that striking similarities remain despite this.

  2. Glutaraldehyde cross-linking of tendon mechanical effects at the level of the tendon fascicle and fibril

    DEFF Research Database (Denmark)

    Hansen, Philip; Hassenkam, Tue; Svensson, Rene Bruggebusch

    2009-01-01

    Conclusive insight into the microscopic principles that govern the strength of tendon and related connective tissues is lacking and the importance of collagen cross-linking has not been firmly established. The combined application of whole-tissue mechanical testing and atomic force spectroscopy......-linking on the tensile properties of a single collagen fibril was investigated by a novel methodology based on atomic force spectroscopy. The Young's modulus of a secluded fibril increased from approximately 407 MPa to approximately 1.1 GPa with glutaraldehyde treatment. Collectively, the findings indicate that cross...

  3. Steroid injections - tendon, bursa, joint

    Science.gov (United States)

    ... gov/ency/article/007678.htm Steroid injections - tendon, bursa, joint To use the sharing features on this ... can be injected into a joint, tendon, or bursa. Description Your health care provider inserts a small ...

  4. Serum- and growth-factor-free three-dimensional culture system supports cartilage tissue formation by promoting collagen synthesis via Sox9-Col2a1 interaction.

    Science.gov (United States)

    Ahmed, Nazish; Iu, Jonathan; Brown, Chelsea E; Taylor, Drew Wesley; Kandel, Rita A

    2014-08-01

    One of the factors preventing clinical application of regenerative medicine to degenerative cartilage diseases is a suitable source of cells. Chondrocytes, the only cell type of cartilage, grown in vitro under culture conditions to expand cell numbers lose their phenotype along with the ability to generate hyaline cartilaginous tissue. In this study we determine that a serum- and growth-factor-free three-dimensional (3D) culture system restores the ability of the passaged chondrocytes to form cartilage tissue in vitro, a process that involves sox9. Bovine articular chondrocytes were passaged twice to allow for cell number expansion (P2) and cultured at high density on 3D collagen-type-II-coated membranes in high glucose content media supplemented with insulin and dexamethasone (SF3D). The cells were characterized after monolayer expansion and following 3D culture by flow cytometry, gene expression, and histology. The early changes in signaling transduction pathways during redifferentiation were characterized. The P2 cells showed a progenitor-like antigen profile of 99% CD44(+) and 40% CD105(+) and a gene expression profile suggestive of interzone cells. P2 in SF3D expressed chondrogenic genes and accumulated extracellular matrix. Downregulating insulin receptor (IR) with HNMPA-(AM3) or the PI-3/AKT kinase pathway (activated by insulin treatment) with Wortmannin inhibited collagen synthesis. HNMPA-(AM3) reduced expression of Col2, Col11, and IR genes as well as Sox6 and -9. Co-immunoprecipitation and chromatin immunoprecipitation analyses of HNMPA-(AM3)-treated cells showed binding of the coactivators Sox6 and Med12 with Sox9 but reduced Sox9-Col2a1 binding. We describe a novel culture method that allows for increase in the number of chondrocytes and promotes hyaline-like cartilage tissue formation in part by insulin-mediated Sox9-Col2a1 binding. The suitability of the tissue generated via this approach for use in joint repair needs to be examined in vivo.

  5. Can transcutaneous electrical nerve stimulation improve achilles tendon healing in rats?

    Directory of Open Access Journals (Sweden)

    Roberta A. C. Folha

    2015-12-01

    Full Text Available BACKGROUND: Tendon injury is one of the most frequent injuries in sports activities. TENS is a physical agent used in the treatment of pain but its influence on the tendon's healing process is unclear. OBJECTIVE: To evaluate the influence of TENS on the healing of partial rupture of the Achilles tendon in rats. METHOD: Sixty Wistar rats were submitted to a partial rupture of the Achilles tendon by direct trauma and randomized into six groups (TENS or Sham stimulation and the time of evaluation (7, 14, and 21 days post-injury. Burst TENS was applied for 30 minutes, 6 days, 100 Hz frequency, 2 Hz burst frequency, 200 µs pulse duration, and 300 ms pulse train duration. Microscopic analyses were performed to quantify the blood vessels and mast cells, birefringence to quantify collagen fiber alignment, and immunohistochemistry to quantify types I and III collagen fibers. RESULTS: A significant interaction was observed for collagen type I (p=0.020 where the TENS group presented lower percentage in 14 days after the lesion (p=0.33. The main group effect showed that the TENS group presented worse collagen fiber alignment (p=0.001 and lower percentage of collagen III (p=0.001 and the main time effect (p=0.001 showed decreased percentage of collagen III at 7 days (p=0.001 and 14 days (p=0.001 after lesion when compared to 21 days. CONCLUSIONS: Burst TENS inhibited collagen I and III production and impaired its alignment during healing of partial rupture of the Achilles tendon in rats.

  6. Tendon Driven Finger Actuation System

    Science.gov (United States)

    Ihrke, Chris A. (Inventor); Reich, David M. (Inventor); Bridgwater, Lyndon (Inventor); Linn, Douglas Martin (Inventor); Askew, Scott R. (Inventor); Diftler, Myron A. (Inventor); Platt, Robert (Inventor); Hargrave, Brian (Inventor); Valvo, Michael C. (Inventor); Abdallah, Muhammad E. (Inventor); hide

    2013-01-01

    A humanoid robot includes a robotic hand having at least one finger. An actuation system for the robotic finger includes an actuator assembly which is supported by the robot and is spaced apart from the finger. A tendon extends from the actuator assembly to the at least one finger and ends in a tendon terminator. The actuator assembly is operable to actuate the tendon to move the tendon terminator and, thus, the finger.

  7. Tendinopathy of the long head of the biceps tendon: histopathologic analysis of the extra-articular biceps tendon and tenosynovium

    Directory of Open Access Journals (Sweden)

    Streit JJ

    2015-03-01

    Full Text Available Jonathan J Streit,1 Yousef Shishani,1 Mark Rodgers,2 Reuben Gobezie1 1The Cleveland Shoulder Institute, 2Department of Pathology, University Hospitals of Cleveland, Cleveland, OH, USA Background: Bicipital tendinitis is a common cause of anterior shoulder pain, but there is no evidence that acute inflammation of the extra-articular long head of the biceps (LHB tendon is the root cause of this condition. We evaluated the histologic findings of the extra-articular portion of the LHB tendon and synovial sheath in order to compare those findings to known histologic changes seen in other tendinopathies. Methods: Twenty-six consecutive patients (mean age 45.4±13.7 years underwent an open subpectoral biceps tenodesis for anterior shoulder pain localized to the bicipital groove. Excised tendons were sent for histologic analysis. Specimens were graded using a semiquantitative scoring system to evaluate tenocyte morphology, the presence of ground substance, collagen bundle characteristics, and vascular changes. Results: Chronic inflammation was noted in only two of 26 specimens, and no specimen demonstrated acute inflammation. Tenocyte enlargement and proliferation, characterized by increased roundness and size of the cell and nucleus with proteoglycan matrix expansion and myxoid degenerative changes, was found in all 26 specimens. Abundant ground substance, collagen bundle changes, and increased vascularization were visualized in all samples. Conclusion: Anterior shoulder pain attributed to the biceps tendon does not appear to be due to an inflammatory process in most cases. The histologic findings of the extra-articular portion of the LHB tendon and synovial sheath are similar to the pathologic findings in de Quervain tenosynovitis at the wrist, and may be due to a chronic degenerative process similar to this and other tendinopathies of the body. Keywords: biceps tendinitis, biceps tendinopathy, tenosynovium, anterior shoulder pain, long head biceps

  8. Clinical aspects of tendon healing

    NARCIS (Netherlands)

    J.C.H.M. van der Meulen (Jacques)

    1974-01-01

    textabstractWe know that healing of a tendon wound takes place by an invasion of fibreblasts from the surrounding tissues; the tendon itself has no intrinsic healing capacity. lt was Potenza (1962) who proved that a traumatic suture of the tendons within their sheath is followed by disintegration of

  9. Open Achilles tendon lacerations.

    Science.gov (United States)

    Said, M Nader; Al Ateeq Al Dosari, Mohamed; Al Subaii, Nasser; Kawas, Alaa; Al Mas, Ali; Al Ser, Yaser; Abuodeh, Yousef; Shakil, Malik; Habash, Ali; Mukhter, Khalid

    2015-04-01

    In contrast to closed Achilles tendon ruptures, open injuries are rarely reported in the literature. This paper provides information about open Achilles tendon wounds that are eventually seen in the Middle East. The reporting unit, Hamad Medical Corporation, is one of the biggest trauma centers in the Gulf area and the major health provider in Qatar. This is a retrospective study including patients admitted and operated for open Achilles tendon injuries between January 2011 and December 2013. Two hundred and five cases of open Achilles tendon lacerations were operated in Hamad General Hospital in this period. Forty-eight cases showed partial injuries, and the remaining are complete tendons cut. In the same period, fifty-one closed ruptured Achilles tendons were operated in the same trauma unit. In the majority of cases, the open injury resulted from a slip in the floor-leveled traditional toilette seats. Local damage to the toilette seats resulted in sharp edges causing the laceration of the heel if the patient was slipping over the wet floor. This occurrence is the cause in the vast majority of the cases. Wounds were located 1-5 cm proximal to tendon insertion. Standard treatment principles were applied. This included thorough irrigation in the emergency room, intravenous antibiotics, surgical debridement and primary repair within 24 h. Patients were kept in the hospital 1-7 days for intravenous antibiotics and possible dressing changes. Postoperatively below knee slabs were applied in the majority of patients and were kept for about 4 weeks followed by gradual weight bearing and range of motion exercises. Outpatients follow up in 1-2 weeks. Further follow-up visits at around 2-, 4-, 8- and 12-week intervals until complete wound healing and satisfactory rehabilitation outcome. Sixteen cases needed a second procedure. A high incidence of Achilles tendon open injuries is reported. This seems to be related to partially damaged floor-level toilettes in the

  10. Immunostimulation effect of jellyfish collagen.

    Science.gov (United States)

    Sugahara, Takuya; Ueno, Masashi; Goto, Yoko; Shiraishi, Ryusuke; Doi, Mikiharu; Akiyama, Koichi; Yamauchi, Satoshi

    2006-09-01

    Certain edible large jellyfishes belonging to the order Rhizostomeae are consumed in large quantities in China and Japan. The exumbrella part of the edible jellyfish Stomolophus nomurai was cut and soaked in dilute hydrochloric acid solution (pH 3.0) for 12 h, and heated at 121 degrees C for 20 min. The immunostimulation effects of the jellyfish extract were examined. The jellyfish extract enhanced IgM production of human hybridoma HB4C5 cells 34-fold. IgM and IgG production of human peripheral blood lymphocytes (PBL) were also accelerated, 2.8- and 1.4-fold respectively. Moreover, production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha by human PBL was stimulated 100- and 17-fold respectively. Collagenase treatment inactivated the immunostimulation activity of the jellyfish extract. In addition, purified collagen from bovine Achilles' tendon accelerated IgM production of hybridoma cells. These facts mean that collagen has an immunostimulation effect, and that the active substance in jellyfish extract is collagen.

  11. Thermal stabilization of collagen in skin and decalcified bone

    Science.gov (United States)

    Miles, Christopher A.; Avery, Nicholas C.

    2011-04-01

    The state of collagen molecules in the fibres of tail tendon, skin and demineralized bone has been investigated in situ using differential scanning calorimetry (DSC). Hydroxyproline analysis and tissue digestion with bacterial collagenase and trypsin were used to confirm that the common cause of all the DSC endotherms was collagen denaturation. This occurred within a narrow temperature range in tendons, but over a wide temperature range in demineralized bone and old skin and demonstrated that in tendon and demineralized bone at least the same type I collagen molecule exists in different thermal states. Hypothesizing that this might be caused by different degrees of confinement within the fibre lattice, experiments were performed to measure the effect of changing the lattice dimensions by extracting the collagen into dilute solution with pepsin, swelling the lattice in acetic acid, and contracting the lattice by dehydration. A theoretical analysis was undertaken to predict the effect of dehydration. Results were consistent with the hypothesis, demonstrating that collagen molecules within the natural fibres of bone and old skin are located at different intermolecular spacings, revealing differences between molecules in the magnitude of either the attractive or repulsive forces controlling their separation. One potential cause of such variation is known differences in covalent cross-linking.

  12. Adherence, proliferation and collagen turnover by human fibroblasts seeded into different types of collagen sponges

    NARCIS (Netherlands)

    Middelkoop, E.; de Vries, H. J.; Ruuls, L.; Everts, V.; Wildevuur, C. H.; Westerhof, W.

    1995-01-01

    We describe an in vitro model that we have used to evaluate dermal substitutes and to obtain data on cell proliferation, the rate of degradation of the dermal equivalent, contractibility and de novo synthesis of collagen. We tested three classes of collagenous materials: (1) reconstituted

  13. ADHERENCE, PROLIFERATION AND COLLAGEN TURNOVER BY HUMAN FIBROBLASTS SEEDED INTO DIFFERENT TYPES OF COLLAGEN SPONGES

    NARCIS (Netherlands)

    MIDDELKOOP, E; DEVRIES, HJC; RUULS, L; EVERTS, [No Value; WILDEVUUR, CHR; WESTERHOF, W

    We describe an in vitro model that we have used to evaluate dermal substitutes and to obtain data on cell proliferation, the rate of degradation of the dermal equivalent, contractibility and de novo synthesis of collagen. We tested three classes of collagenous materials: (1) reconstituted

  14. Anisotropy of chemical bonds in collagen molecules studied by X-ray absorption near-edge structure (XANES) spectroscopy.

    Science.gov (United States)

    Lam, Raymond S K; Metzler, Rebecca A; Gilbert, Pupa U P A; Beniash, Elia

    2012-03-16

    Collagen type I fibrils are the major building blocks of connective tissues. Collagen fibrils are anisotropic supramolecular structures, and their orientation can be revealed by polarized light microscopy and vibrational microspectroscopy. We hypothesized that the anisotropy of chemical bonds in the collagen molecules, and hence their orientation, might also be detected by X-ray photoemission electron spectromicroscopy (X-PEEM) and X-ray absorption near-edge structure (XANES) spectroscopy, which use linearly polarized synchrotron light. To test this hypothesis, we analyzed sections of rat-tail tendon, composed of parallel arrays of collagen fibrils. The results clearly indicate that XANES-PEEM is sensitive to collagen fibril orientation and, more specifically, to the orientations of carbonyl and amide bonds in collagen molecules. These data suggest that XANES-PEEM is a promising technique for characterizing the chemical composition and structural organization at the nanoscale of collagen-based connective tissues, including tendons, cartilage, and bone.

  15. Effects of ethanol and acetaldehyde on collagen synthesis, prostaglandin release and resorption of fetal rat bone in organ culture.

    Science.gov (United States)

    Hurley, M M; Martin, D L; Kream, B E; Raisz, L G

    1990-01-01

    We tested the effect of ethanol and its metabolite, acetaldehyde, on bone formation as measured by [3H]proline incorporation into collagenase digestible protein (CDP) and noncollagen protein (NCP), and on DNA synthesis as measured by [3H]thymidine (TdR) incorporation in fetal rat calvaria. We also determined the effects of ethanol and acetaldehyde on prostaglandin E2 (PGE2) release from calvaria and on bone resorption as measured by 45Ca release from fetal rat long bones. Bones were cultured in multiwell plastic dishes (open system) or in stoppered Erlenmeyer flasks (closed system) for 24 to 96 h. In the open system, 1% ethanol (v/v; 172 mM) resulted in a 31% decrease in TdR incorporation at 24 h with no effect on CDP and NCP. At 0.1% (17.2 mM), ethanol increased TdR by 22%, CDP by 73% and NCP by 67% at 24 h, but these effects were not sustained at 96 h. At 24 h, 1% and 0.3% ethanol decreased PGE2 release by 88% and 75% respectively. This effect was sustained for 96 h only at the higher concentration. In the closed system, 0.1% ethanol increased TdR incorporation by 38% at 24 h. However, there was no effect on the labeling of CDP or NCP. Because its boiling point is 21 degrees C, acetaldehyde could only be tested in the closed system. Acetaldehyde markedly inhibited bone metabolism. At 24 h, 0.003% (0.54 mM) to 0.01% (1.79 mM) acetaldehyde caused a dose-related inhibition of TdR incorporation from 23 to 45%. At 0.01% and 0.03% acetaldehyde inhibited proline incorporation into CDP by 48% and 94% and NCP by 40% and 74% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Preparation of (3H)collagen for studies of the biologic fate of xenogenic collagen implants in vivo

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, J.M.; Sawamura, S.J.; Conti, A.

    1986-06-01

    Reduction of a commercially available, pepsin-solubilized, bovine dermal collagen (Vitrogen 100) with sodium (3H)borohydride provided radiolabeled collagen preparations with specific activities ranging from 7.1-12.0 muCi/mg collagen. These specific activities were 2-3 times greater than those obtained by reduction of intact rat tail tendon collagen under similar conditions. The alpha, beta, and higher aggregate components of type I collagen were radiolabeled as well as the alpha component of a small amount of type III collagen present in the samples. Fractionation of cyanogen bromide peptides showed that alpha 1(I)CB7, alpha 1(I)CB8, and alpha 2(I)CB3,5 were the predominant peptides labeled by this procedure. Amino acid analysis indicated that the majority of the radioactivity was in reducible cross-links, precursors of these cross-links, and in hexosyllysine residues. Reconstitution experiments comparing this radiolabeled collagen with nonlabeled collagen showed them to be indistinguishable. Bacterial collagenase digestion of this reconstituted fibrillar collagen in both a lightly cross-linked (glutaraldehyde 0.0075%) and noncross-linked form provided evidence that digestion of labeled and nonlabeled collagens proceeded at similar rates. Thus, labeling did not change the properties of the collagen. Cross-linking made the preparation refractory to proteolytic degradation. Injection of fibrillar collagen preparations, spiked with radiolabeled collagen, into the guinea pig dermis followed by quantitation of the amount of radioactivity recovered from implant sites as a function of time, indicated that the lightly cross-linked samples also were more resistant to degradation in vivo than the noncross-linked preparation. The half-life of noncross-linked collagen was about 4 days while that of the cross-linked collagen was about 25 days.

  17. The influence of physical activity during youth on structural and functional properties of the Achilles tendon

    DEFF Research Database (Denmark)

    Lenskjold, A; Kongsgaard, M; Larsen, J O

    2015-01-01

    were either physically active (HAY) or inactive (LAY) in young age. Twelve men in HAY group and eight men in LAY group participated. Structural, functional, and biochemical properties of Achilles tendon were estimated from magnetic resonance imaging, ultrasound video recordings, mechanical tests......-link density did not differ between the groups, nor did collagen fibril density, diameter, and area. There was a correlation between age and pentosidine/collagen within the groups [(HAY: P activity during youth...

  18. Collagen tissue engineering: development of novel biomaterials and applications.

    Science.gov (United States)

    Cen, Lian; Liu, Wei; Cui, Lei; Zhang, Wenjie; Cao, Yilin

    2008-05-01

    Scientific investigations involving collagen have inspired tissue engineering and design of biomaterials since collagen fibrils and their networks primarily regulate and define most tissues. The collagen networks form a highly organized, three-dimensional architecture to entrap other ingredients. Biomaterials are expected to function as cell scaffolds to replace native collagen-based extracellular matrix. The composition and properties of biomaterials used as scaffold for tissue engineering significantly affect the regeneration of neo-tissues and influence the conditions of collagen engineering. The complex scenario of collagen characteristics, types, fibril arrangement, and collagen structure-related functions (in a variety of connective tissues including bone, cartilage, tendon, skin and cornea) are addressed in this review. Discussion will focus on nanofibrillar assemblies and artificial synthetic peptides that mimic either the fibrillar structure or the elemental components of type I collagen as illustrated by their preliminary applications in tissue engineering. Conventional biomaterials used as scaffolds in engineering collagen-containing tissues are also discussed. The design of novel biomaterials and application of conventional biomaterials will facilitate development of additional novel tissue engineering bioproducts by refining the currently available techniques. The field of tissue engineering will ultimately be advanced by increasing control of collagen in native tissue and by continual manipulation of biomaterials.

  19. Achilles tendon rupture - aftercare

    Science.gov (United States)

    ... will cover your foot and go to your knee. Your toes will be pointing downward. The cast will be changed every 2 to 3 weeks to help stretch your tendon. If you have a leg brace, splint, or boot, it will keep you from ...

  20. Tendon Is Covered by a Basement Membrane Epithelium That Is Required for Cell Retention and the Prevention of Adhesion Formation

    Science.gov (United States)

    Taylor, Susan H.; Al-Youha, Sarah; Van Agtmael, Tom; Lu, Yinhui; Wong, Jason; McGrouther, Duncan A.; Kadler, Karl E.

    2011-01-01

    The ability of tendons to glide smoothly during muscle contraction is impaired after injury by fibrous adhesions that form between the damaged tendon surface and surrounding tissues. To understand how adhesions form we incubated excised tendons in fibrin gels (to mimic the homeostatic environment at the injury site) and assessed cell migration. We noticed cells exiting the tendon from only the cut ends. Furthermore, treatment of the tendon with trypsin resulted in cell extravagation from the shaft of the tendons. Electron microscopy and immunolocalisation studies showed that the tendons are covered by a novel cell layer in which a collagen type IV/laminin basement membrane (BM) overlies a keratinised epithelium. PCR and western blot analyses confirmed the expression of laminin β1 in surface cells, only. To evaluate the cell retentive properties of the BM in vivo we examined the tendons of the Col4a1+/Svc mouse that is heterozygous for a G-to-A transition in the Col4a1 gene that produces a G1064D substitution in the α1(IV) chain of collagen IV. The flexor tendons had a discontinuous BM, developed fibrous adhesions with overlying tissues, and were acellular at sites of adhesion formation. In further experiments, tenotomy of wild-type mice resulted in expression of laminin throughout the adhesion. In conclusion, we show the existence of a novel tendon BM-epithelium that is required to prevent adhesion formation. The Col4a1+/Svc mouse is an effective animal model for studying adhesion formation because of the presence of a structurally-defective collagen type IV-containing BM. PMID:21298098

  1. Tendon is covered by a basement membrane epithelium that is required for cell retention and the prevention of adhesion formation.

    Directory of Open Access Journals (Sweden)

    Susan H Taylor

    2011-01-01

    Full Text Available The ability of tendons to glide smoothly during muscle contraction is impaired after injury by fibrous adhesions that form between the damaged tendon surface and surrounding tissues. To understand how adhesions form we incubated excised tendons in fibrin gels (to mimic the homeostatic environment at the injury site and assessed cell migration. We noticed cells exiting the tendon from only the cut ends. Furthermore, treatment of the tendon with trypsin resulted in cell extravagation from the shaft of the tendons. Electron microscopy and immunolocalisation studies showed that the tendons are covered by a novel cell layer in which a collagen type IV/laminin basement membrane (BM overlies a keratinised epithelium. PCR and western blot analyses confirmed the expression of laminin β1 in surface cells, only. To evaluate the cell retentive properties of the BM in vivo we examined the tendons of the Col4a1(+/Svc mouse that is heterozygous for a G-to-A transition in the Col4a1 gene that produces a G1064D substitution in the α1(IV chain of collagen IV. The flexor tendons had a discontinuous BM, developed fibrous adhesions with overlying tissues, and were acellular at sites of adhesion formation. In further experiments, tenotomy of wild-type mice resulted in expression of laminin throughout the adhesion. In conclusion, we show the existence of a novel tendon BM-epithelium that is required to prevent adhesion formation. The Col4a1(+/Svc mouse is an effective animal model for studying adhesion formation because of the presence of a structurally-defective collagen type IV-containing BM.

  2. Adipose derived stromal vascular fraction improves early tendon healing: an experimental study in rabbits

    Directory of Open Access Journals (Sweden)

    Mehdi Behfar

    2011-11-01

    Full Text Available Tendon never restores the complete biological and mechanical properties after healing. Bone marrow and recently adipose tissue have been used as the sources of mesenchymal stem cells, which have been proven to enhance tendon healing. Stromal vascular fraction (SVF, derived from adipose tissue by an enzymatic digestion, represents an alternative source of multipotent cells, which undergo differentiation into multiple lineages to be used in regenerative medicine. In the present study, we investigated potentials of this source on tendon healing. Twenty rabbits were divided into control and treatment groups. Five rabbits were used as donors of adipose tissue. The injury model was unilateral complete transection through the middle one third of deep digital flexor tendon. Immediately after suture repair, either fresh stromal vascular fraction from enzymatic digestion of adipose tissue or placebo was intratendinously injected into the suture site in treatments and controls, respectively. Cast immobilization was continued for two weeks after surgery. Animals were sacrificed at the third week and tendons underwent histological, immunohistochemical, and mechanical evaluations. By histology, improved fibrillar organization and remodeling of neotendon were observed in treatment group. Immunohistochemistry revealed an insignificant increase in collagen type III and I expression in treatments over controls. Mechanical testing showed significant increase in maximum load and energy absorption in SVF treated tendons. The present study showed that intratendinous injection of uncultured adipose derived stromal vascular fraction improved structural and mechanical properties of repaired tendon and it could be an effective modality for treating tendon laceration.

  3. The effect of dry needling and treadmill running on inducing pathological changes in rat Achilles tendon.

    Science.gov (United States)

    Kim, Bom Soo; Joo, Young Chae; Choi, Byung Hyune; Kim, Kil Hwan; Kang, Joon Soon; Park, So Ra

    2015-11-01

    Achilles tendinopathy is a common degenerative condition without a definitive treatment. An adequate chronic animal model of Achilles tendinopathy has not yet been developed. The purpose of this study was to evaluate the individual and combined effects of dry needling and treadmill running on the Achilles tendon of rats. Percutaneous dry needling, designed to physically replicate microrupture of collagen fibers in overloaded tendons, was performed on the right Achilles tendon of 80 Sprague-Dawley rats. The rats were randomly divided into two groups: a treadmill group, which included rats that underwent daily uphill treadmill running (n = 40), and a cage group, which included rats that could move freely within their cages (n = 40). At the end of weeks 1 and 4, 20 rats from each group were sacrificed, and bilateral Achilles tendons were collected. The harvested tendons were subjected to mechanical testing and histological analysis. Dry needling induced histological and mechanical changes in the Achilles tendons at week 1, and the changes persisted at week 4. The needled Achilles tendons of the treadmill group tended to show more severe histological and mechanical changes than those of the cage group, although these differences were not statistically significant. Dry needling combined with free cage activity or treadmill running produced tendinopathy-like changes in rat Achilles tendons up to 4 weeks after injury. Dry needling is an easy procedure with a short induction period and a high success rate, suggesting it may have relevance in the design of an Achilles tendinopathy model.

  4. Collagen types I, III, and V constitute the thick collagen fibrils of the mouse decidua.

    Science.gov (United States)

    Spiess, Karin; Zorn, Telma Maria Tenório

    2007-01-01

    A mammal's endometrium is deeply remodeled while receiving and implanting an embryo. In addition to cell proliferation and growth, endometrial remodeling also comprises synthesis and degradation of several molecular components of the extracellular matrix. All of these events are orchestrated by a precise sequence of ovarian hormones and influenced by several types of cytokines. As we have previously reported, an intriguing and rapid increase in collagen fibril diameter occurs in the decidualized areas of the endometrium, surrounding the implantation crypt, whereas collagen fibrils situated far from the embryo remain unchanged. Collagen fibrilogenesis is a complex molecular process coordinated by a number of factors, such as the types and amounts of glycosaminoglycans and proteoglycans associated with collagen molecules. Collagen genetic type, mechanical stress, aging, and other factors not yet identified also contribute to this development. A recent study suggests that thick fibrils from mouse decidua are formed, at least in part, by aggregation of thin fibrils existing in the stroma before the onset of decidualization. In the present ultrastructural study using single and double immunogold localization, we showed that both thin and thick collagen fibrils present in the mouse pregnant endometrium endometrium are heterotypic structures formed at least by type I, type III, and type V collagens. However, type V collagen predominates in the thick collagen fibrils, whereas it is almost absent of the thin collagen fibrils. The putative role of type V homotrimer in the rapid increase of the diameter of collagen fibrils of the mouse decidua is discussed.

  5. Transplantation of Achilles Tendon Treated With Bone Morphogenetic Protein 7 Promotes Meniscus Regeneration in a Rat Model of Massive Meniscal Defect

    Science.gov (United States)

    Ozeki, Nobutake; Muneta, Takeshi; Koga, Hideyuki; Katagiri, Hiroki; Otabe, Koji; Okuno, Makiko; Tsuji, Kunikazu; Kobayashi, Eiji; Matsumoto, Kenji; Saito, Hirohisa; Saito, Tomoyuki; Sekiya, Ichiro

    2013-01-01

    Objective This study was undertaken to examine whether bone morphogenetic protein 7 (BMP-7) induces ectopic cartilage formation in the rat tendon, and whether transplantation of tendon treated with BMP-7 promotes meniscal regeneration. Additionally, we analyzed the relative contributions of host and donor cells on the healing process after tendon transplantation in a rat model. Methods BMP-7 was injected in situ into the Achilles tendon of rats, and the histologic findings and gene profile were evaluated. Achilles tendon injected with 1 μg of BMP-7 was transplanted into a meniscal defect in rats. The regenerated meniscus and articular cartilage were evaluated at 4, 8, and 12 weeks. Achilles tendon from LacZ-transgenic rats was transplanted into the meniscal defect in wild-type rats, and vice versa. Results Injection of BMP-7 into the rat Achilles tendon induced the fibrochondrocyte differentiation of tendon cells and changed the collagen gene profile of tendon tissue to more closely approximate meniscal tissue. Transplantation of the rat Achilles tendon into a meniscal defect increased meniscal size. The rats that received the tendon treated with BMP-7 had a meniscus matrix that exhibited increased Safranin O and type II collagen staining, and showed a delay in articular cartilage degradation. Using LacZ-transgenic rats, we determined that the regeneration of the meniscus resulted from contribution from both donor and host cells. Conclusion Our findings indicate that BMP-7 induces ectopic cartilage formation in rat tendons. Transplantation of Achilles tendon treated with BMP-7 promotes meniscus regeneration and prevents cartilage degeneration in a rat model of massive meniscal defect. Native cells in the rat Achilles tendon contribute to meniscal regeneration. PMID:23897174

  6. Tendon injuries of the hand

    Science.gov (United States)

    Schöffl, Volker; Heid, Andreas; Küpper, Thomas

    2012-01-01

    Tendon injuries are the second most common injuries of the hand and therefore an important topic in trauma and orthopedic patients. Most injuries are open injuries to the flexor or extensor tendons, but less frequent injuries, e.g., damage to the functional system tendon sheath and pulley or dull avulsions, also need to be considered. After clinical examination, ultrasound and magnetic resonance imaging have proved to be important diagnostic tools. Tendon injuries mostly require surgical repair, dull avulsions of the distal phalanges extensor tendon can receive conservative therapy. Injuries of the flexor tendon sheath or single pulley injuries are treated conservatively and multiple pulley injuries receive surgical repair. In the postoperative course of flexor tendon injuries, the principle of early passive movement is important to trigger an “intrinsic” tendon healing to guarantee a good outcome. Many substances were evaluated to see if they improved tendon healing; however, little evidence was found. Nevertheless, hyaluronic acid may improve intrinsic tendon healing. PMID:22720265

  7. Mechanical stimulation (pulsed electromagnetic fields "PEMF" and extracorporeal shock wave therapy "ESWT" and tendon regeneration: a possible alternative.

    Directory of Open Access Journals (Sweden)

    Federica eRosso

    2015-11-01

    Full Text Available The pathogenesis of tendon degeneration and tendinopathy is still partially unclear. However, an active role of metalloproteinases (MMP, growth factors, such as vascular endothelial growth factor (VEGF and a crucial role of inflammatory elements and cytokines was demonstrated. Mechanical stimulation may play a role in regulation of inflammation. In vitro studies demonstrated that both pulsed electromagnetic fields (PEMF and extracorporeal shock wave therapy (ESWT increased the expression of pro-inflammatory cytokine such as interleukin (IL-6 and IL-10. Moreover ESWT increases the expression of growth factors, such as transforming growth factor beta (TGF-beta, Vascular Endothelial Growth Factor (VEGF, and insulin-like growth factor 1 (IGF1, as well as the synthesis of collagen I fibers. These pre-clinical results, in association with several clinical studies, suggest a potential effectiveness of ESWT for tendinopathy treatment. Recently PEMF gained popularity as adjuvant for fracture healing and bone regeneration. Similarly to ESWT, the mechanical stimulation obtained using PEMFs may play a role for treatment of tendinopathy and for tendon regeneration, increasing in-vitro TGF-beta production, as well as scleraxis and collagen I gene expression. In this manuscript the rational of mechanical stimulations and the clinical studies on the efficacy of extracorporeal shock wave (ESW and PEMF will be discussed. However, no clear evidence of a clinical value of ESW and PEMF has been found in literature with regards to the treatment of tendinopathy in human, so further clinical trials are needed to confirm the promising hypotheses concerning the effectiveness of ESWT and PEMF mechanical stimulation.

  8. Low-Level Light Therapy with 410 nm Light Emitting Diode Suppresses Collagen Synthesis in Human Keloid Fibroblasts: An In Vitro Study

    OpenAIRE

    Lee, Hyun Soo; Jung, Soo-Eun; Kim, Sue Kyung; Kim, You-Sun; Sohn, Seonghyang; Kim, You Chan

    2017-01-01

    Background Keloids are characterized by excessive collagen deposition in the dermis, in which transforming growth factor ? (TGF-?)/Smad signaling plays an important role. Low-level light therapy (LLLT) is reported as effective in preventing keloids in clinical reports, recently. To date, studies investigating the effect of LLLT on keloid fibroblasts are extremely rare. Objective We investigated the effect of LLLT with blue (410 nm), red (630 nm), and infrared (830 nm) light on the collagen sy...

  9. The Effects of a Crosslinked, Modified Hyaluronic Acid (xCMHA-S) Gel on Equine Tendon Healing.

    Science.gov (United States)

    Jann, Henry W; Hart, James C A; Stein, Larry E; Ritchey, Jerry; Blaik, Margaret; Payton, Mark; Fackelman, Gustave E; Rezabek, Grant B; Mann, Brenda K

    2016-02-01

    To assess the effects of a crosslinked, modified hyaluronic acid (xCMHA-S) gel on equine tendon healing using an in vivo surgical model. In vivo experimental study. Adult horses (n = 5). Full thickness bilateral forelimb window tenectomies were surgically created in both forelimb superficial digital flexor tendons and xCMHA-S gel was implanted intraoperatively into the right forelimb lesion of each horse whereas the left forelimb served as the untreated control. Healing was monitored by serial ultrasound examinations every 14 days over the course of the 84 day study. In addition, gross pathology, scanning electron microscopy for fiber diameter, and histological scoring were completed on tendon samples harvested after euthanasia at 84 days. Ultrasound assessment demonstrated a significant decrease in mean lesion size of treated (0%) compared to control (30%) tendons at 84 days. Mean (±SD) cumulative histologic tendon scores for control tendons (17.7 ± 2.7) were significantly higher than treated tendons (13.6 ± 1.9), indicating less advanced healing in the control group. Tendon cell density was increased and neovascularization, intensity of inflammation, and uniformity of fiber diameter were increased in control compared to treated tendons. There were no differences in fibroblast shape, levels of intralesional hemorrhage, linearity of collagen fibers, or collagen fiber diameter or distribution between treated and control tendons. Tendons treated with xCMHA-S gel at the time of model induction had superior histologic healing scores and sonographically smaller lesions compared to controls, suggesting that xCMHA-S gel may aid the natural healing process. © Copyright 2016 by The American College of Veterinary Surgeons.

  10. Effects of fish collagen peptides on collagen post-translational modifications and mineralization in an osteoblastic cell culture system.

    Science.gov (United States)

    Yamada, Shizuka; Nagaoka, Hideaki; Terajima, Masahiko; Tsuda, Nobuaki; Hayashi, Yoshihiko; Yamauchi, Mitsuo

    2013-01-01

    Collagen is one of the most widely used biomaterials for tissue engineering and regenerative medicine. Fish collagen peptides (FCP) have been used as a dietary supplement, but their effects on the cellular function are still poorly understood. The objective of this study was to investigate the effects of FCP on collagen synthesis, quality and mineralization using an osteoblastic MC3T3-E1 cell culture system. Cells treated with FCP significantly upregulated the gene expression of several collagen modifying enzymes and more collagen was deposited in the cultures. Collagen in the treated group showed a greater extent of lysine hydroxylation, higher levels of hydroxylysine-aldehyde derived cross-links and accelerated cross-link maturation compared with the untreated group. Furthermore, the treated group showed accelerated matrix mineralization. These results indicate that FCP exerts a positive effect on osteoblastic cells in terms of collagen synthesis, quality and mineralization, thereby suggesting the potential utility of FCP for bone tissue engineering.

  11. Miscellaneous conditions of tendons, tendon sheaths, and ligaments.

    Science.gov (United States)

    Dyson, S J; Dik, K J

    1995-08-01

    The use of diagnostic ultrasonography has greatly enhances our ability to diagnose injuries of tendons and tendon sheaths that were previously either unrecognized or poorly understood. For may of these injuries, there is currently only a small amount of follow-up data. This article considers injuries of the deep digital flexor tendon and its accessory ligament, the carpal tunnel syndrome soft tissue swellings on the dorsal aspect of the carpus, intertubercular (bicipital) bursitis and bicipital tendinitis, injuries of the gastrocnemius tendon, common calcaneal tendinitis, rupture of peroneus (fibularis tertius) and ligaments injuries of the back.

  12. Exercise & NSAID: Effect on muscle protein synthesis in knee osteoarthritis patients?

    DEFF Research Database (Denmark)

    Petersen, S.G.; Miller, Ben F; Hansen, M

    2011-01-01

    the exercise-induced response of muscle contractile protein FSR. However, we cannot exclude that a minor inhibition of muscle sarcoplasmic proteins may have been present with NSAID treatment. This study suggests that muscle hypertrophy after long-term training is not influenced by NSAIDs.......PURPOSE:The purpose of this study was to determine muscle and tendon protein fractional synthesis rates (FSR) at rest and after a one-legged kicking exercise in patients with knee osteoarthritis (OA) receiving either placebo or nonsteroidal anti-inflammatory drugs (NSAIDs).METHODS:Twenty patients...... the contralateral leg remained rested. Twenty-four hours after exercise, we determined circulating concentrations of inflammatory parameters and measured FSR of myofibrillar and sarcoplasmic protein fractions of vastus lateralis muscle and patellar tendon collagen protein by the direct incorporation method using...

  13. MRI of the Achilles tendon

    Energy Technology Data Exchange (ETDEWEB)

    Naegele, M.; Lienemann, A.; Hahn, D.; Lissner, J.; Boehm, P.

    1987-06-01

    The Achilles tendon and preachillar space of 30 patients was studied by MRI. A surface coil (Helmholtz' principle) was applied and all patients were examined with a superconducting magnet operating at 1.0 Tesla field strength. The purpose of the study was to illustrate pathological changes of the tendon and the surrounding soft tissue. In 3 cases MRI diagnosed a total rupture of the Achilles tendon. Furthermore, the strain of the tendon and side effects of an inflammatory process could be demonstrated. The use of a surface coil yields a high resolution of the normal anatomy of the region and of the pathological changes of the tendon and the surrounding soft tissue structures. The advantages of MRI for Achilles tendon diagnostics against competitive modalities are 1) excellent soft tissue contrast, 2) multiplanar imaging, 3) as well as exact delineation and visualisation of the lesion.

  14. Contribution of glycosaminoglycans to the microstructural integrity of fibrillar and fiber crimps in tendons and ligaments.

    Science.gov (United States)

    Franchi, Marco; De Pasquale, Viviana; Martini, Désirée; Quaranta, Marilisa; Macciocca, Maria; Dionisi, Alessio; Ottani, Vittoria

    2010-10-01

    The biomechanical roles of both tendons and ligaments are fulfilled by the extracellular matrix of these tissues. In particular, tension is mainly transmitted and resisted by protein (collagen, elastin) fibers, whereas compression is opposed by water-soluble glycosaminoglycans (GAGs). GAGs spanning the interfibrillar spaces and interacting with fibrils through the interfibrillar proteoglycans also seem to play a part in transmitting and resisting tensile stresses. Both tendons and ligaments showing similar composition, but different functional roles and collagen array, exhibit periodic undulations of collagen fibers or crimps. Each crimp is composed of many knots of each single fibril or fibrillar crimps. Fibrillar and fiber crimps play a mechanical role in absorbing the initial loading during elongation of both tendons and ligaments, and in recoiling fibrils and fibers when tissues have to return to their original length. This study investigated whether GAGs covalently attached to proteoglycan core proteins directly affect the 3D microstructural integrity of fibrillar crimp regions and fiber crimps in both tendons and ligaments. Achilles tendons and medial collateral ligaments of the knee from eight female Sprague-Dawley rats (90 days old) incubated in a chondroitinase ABC solution to remove GAGs were observed under a scanning electron microscope (SEM). In addition, isolated fibrils of these tissues obtained by mechanical disruption were analyzed by a transmission electron microscope (TEM). Both Achilles tendons and medial collateral ligaments of the rats after chemical or mechanical removal of GAGs still showed crimps and fibrillar crimps comparable to tissues with a normal GAG content. All fibrils in the fibrillar crimp region always twisted leftwards, thus changing their running plane, and then sharply bent, changing their course on a new plane. These data suggest that GAGs do not affect structural integrity or fibrillar crimp functions that seem mainly related

  15. Experimental intrinsic healing of flexor tendons based upon synovial fluid nutrition.

    Science.gov (United States)

    Lundborg, G; Rank, F

    1978-01-01

    The healing process of totally cut and subsequently resutured rabbit flexor tendons kept isolated in the knee joint cavity and free in the synovial fluid was studied by histological and ultrastructural techniques. This experimental model represents a "tissue culture in situ," where the tendon is nourished by diffusion from the synovial fluid only and where no adhesions are formed. Under these conditions there is a proliferation of tendon cells and deposition of collagen resulting in bridging of the suture line. On the basis of these findings, it is assumed that the tendon cells possess an intrinsic potential of repair, provided they obtain a sufficient nutritional supply. In the present experimental model, this nutrition was provided by way of diffusional pathways from the synovial fluid.

  16. Epigallocatechin-3-gallate inhibits transforming-growth-factor-β1-induced collagen synthesis by suppressing early growth response-1 in human buccal mucosal fibroblasts.

    Science.gov (United States)

    Hsieh, Yu-Ping; Chen, Hsin-Ming; Lin, Hung-Ying; Yang, Hsiang; Chang, Jenny Zwei-Chieng

    2017-02-01

    Transforming growth factor (TGF)-β is a key regulator in the pathogenesis of oral submucous fibrosis (OSF). Early growth response (Egr)-1 is essential for fibrotic responses to TGF-β. Because TGF-β signaling is cell-type- and context-dependent, we investigated the signaling involved in TGF-β-induced Egr-1 in primary human buccal mucosal fibroblasts (BMFs). TGF-β-induced Egr-1 and its signaling were assessed by western blotting in BMFs. Egr-1 small interfering RNA was used to define the role of Egr-1 on TGF-β-induced mRNAs of the α1- and α2-chains of type I collagen (COL1A1 and COL1A2) and acid-soluble collagen production (via Sircol collagen assay). The effects of epigallocatechin-3-gallate (EGCG) on TGF-β-induced Egr-1 protein and acid-soluble collagen were also evaluated. TGF-β1 stimulated Egr-1 production in BMFs. Pretreatment with PD98059, SP600125, SB431542, and SIS3, but not SB203580, significantly reduced TGF-β1-induced Egr-1 protein expression. Genetic targeting of Egr-1 completely inhibited TGF-β1-induced type I collagen mRNAs and collagen protein expression. EGCG fully inhibited TGF-β1-induced Egr-1 and TGF-β1-stimulated production of acid-soluble collagens. We conclude that activin receptor-like kinase (ALK)5, Smad3, extracellular signal-regulated kinase, and c-Jun N-terminal kinase are involved in the TGF-β1-induced Egr-1 protein production in BMFs. Egr-1 mediates TGF-β1-induced COL1A1 and COL1A2 mRNA expression and acid-soluble collagen production in BMFs. EGCG can block TGF-β1-induced collagen production by attenuating Egr-1 expression in BMFs. Egr-1 is a key mediator in TGF-β1-induced pathogenesis of OSF. EGCG may be useful in the prevention or treatment of OSF. Copyright © 2016. Published by Elsevier B.V.

  17. Laser welding and collagen crosslinks

    Energy Technology Data Exchange (ETDEWEB)

    Reiser, K.M.; Last, J.A. [California Univ., Davis, CA (United States). Dept. of Medicine; Small, W. IV; Maitland, D.J.; Heredia, N.J.; Da Silva, L.B.; Matthews, D.L. [Lawrence Livermore National Lab., CA (United States)

    1997-02-20

    Strength and stability of laser-welded tissue may be influenced, in part, by effects of laser exposure on collagen crosslinking. We therefore studied effects of diode laser exposure (805 nm, 1-8 watts, 30 seconds) + indocyanine green dye (ICG) on calf tail tendon collagen crosslinks. Effect of ICG dye alone on crosslink content prior to laser exposure was investigated; unexpectedly, we found that ICG-treated tissue had significantly increased DHLNL and OHP, but not HLNL. Laser exposure after ICG application reduced elevated DHLNL and OHP crosslink content down to their native levels. The monohydroxylated crosslink HLNL was inversely correlated with laser output (p<0.01 by linear regression analysis). DHLNL content was highly correlated with content of its maturational product, OHP, suggesting that precursor-product relations are maintained. We conclude that: (1)ICG alone induces DHLNL and OHP crosslink formation; (2)subsequent laser exposure reduces the ICG-induced crosslinks down to native levels; (3)excessive diode laser exposure destroys normally occurring HLNL crosslinks.

  18. Fibroma of the tendon sheath - a rare hand tumor.

    Science.gov (United States)

    Heckert, Reed; Bear, Jonathan; Summers, Thomas; Frew, Michael; Gwinn, David; McKay, Patricia

    2012-12-01

    Fibroma of the tendon sheath (FTS) is a rare, benign, soft tissue lesion. Clinically, FTS presents similarly to the more common giant cell tumor of the tendon sheath. It is distinguished histologically by the lack of giant cells, foamy histiocytes and synovial cells. We presented a case of FTS involving the common tendon sheath surrounding the flexor tendons leading to the third metacarpal. A 63-year-old man presented with a 3-month history of a painless mass in his right palm that had recently tripled in size. Examination demonstrated a 5x4 cm firm, nodular, superficial mass that was adherent to the overlying skin. Radiographs of the hand revealed a soft tissue mass without bony abnormality. Ultrasound demonstrated a solid, heterogeneous and hypoechoic mass and computed tomography demonstrated that the mass centered predominantly at the mid and distal portions of the third metacarpal. The patient underwent excisional biopsy of the lesion and a palmar, longitudinal incision was made from the wrist to the third metacarpal. Submitted histologic sections revealed a well-circumscribed lesion closely resembling hyalinized collagen. Neither vascular proliferations, necrosis, nor mitoses were observed. Similarly, multinucleated giant cells, pigment-laden macrophages, and inflammatory cells were also not identified. A diagnosis of FTS was rendered. We provided an additional rare case to the literature of a FTS and highlight the need to consider this entity in the differential diagnosis for any soft tissue lesion in the hand. Three months post surgery the patient demonstrated full range of motion of the hand.

  19. Effects of montelukast sodium on tendon healing: An experimental study

    Directory of Open Access Journals (Sweden)

    Atilla Polat

    2013-01-01

    Full Text Available Introduction: Montelukast sodium (MS a selective leukotriene antagonist of the cysteinyl leukotriene receptor, has been used in the treatment of asthma and allergic rhinitis. In this study, we evaluated the effect of MS on the early inflammatory phase (histological of nonsynovial tendon healing. Materials and Methods: Rats were divided randomly into two groups (n = 6 each. MS (Singulair was administered to one group at 10 mg/kg/day [250 g/day intraperitoneally (i.p.]. The control group was administered 250 g/day of 0.9% saline i.p. This nonsynovial tendon was longitudinally divided at the midportion, cut transversely and then sutured. In both groups, the rats were sacrificed by decapitation 10 days later. Results: Decreased inflammatory cell infiltration and more properly oriented collagen fibres were observed in the MS group′s histopathological specimens as compared to the control group′s (P < 0.05. Additionally, vascularity was decreased in the MS group. Conclusion: MS decreased tendon healing, apparently by inhibiting the early inflammatory phase of nonsynovial tendon healing.

  20. The effects of scaffold architecture and fibrin gel addition on tendon cell phenotype.

    Science.gov (United States)

    Pawelec, K M; Wardale, R J; Best, S M; Cameron, R E

    2015-01-01

    Development of tissue engineering scaffolds relies on careful selection of pore architecture and chemistry of the cellular environment. Repair of skeletal soft tissue, such as tendon, is particularly challenging, since these tissues have a relatively poor healing response. When removed from their native environment, tendon cells (tenocytes) lose their characteristic morphology and the expression of phenotypic markers. To stimulate tendon cells to recreate a healthy extracellular matrix, both architectural cues and fibrin gels have been used in the past, however, their relative effects have not been studied systematically. Within this study, a combination of collagen scaffold architecture, axial and isotropic, and fibrin gel addition was assessed, using ovine tendon-derived cells to determine the optimal strategy for controlling the proliferation and protein expression. Scaffold architecture and fibrin gel addition influenced tendon cell behavior independently in vitro. Addition of fibrin gel within a scaffold doubled cell number and increased matrix production for all architectures studied. However, scaffold architecture dictated the type of matrix produced by cells, regardless of fibrin addition. Axial scaffolds, mimicking native tendon, promoted a mature matrix, with increased tenomodulin, a marker for mature tendon cells, and decreased scleraxis, an early transcription factor for connective tissue. This study demonstrated that both architectural cues and fibrin gel addition alter cell behavior and that the combination of these signals could improve clinical performance of current tissue engineering constructs.

  1. The Use of Hyaluronic Acid after Tendon Surgery and in Tendinopathies

    Directory of Open Access Journals (Sweden)

    Michele Abate

    2014-01-01

    Full Text Available Viscosupplementation with hyaluronic acid is safe and effective in the management of osteoarthritis, but its use in the treatment of tendon disorders has received less attention. The aim of this review is to summarize the current knowledge on this topic, evaluating experimental and clinical trials. A search of English-language articles was performed using the key search terms “hyaluronic acid” or “viscosupplementation” combined with “tendon,” “tendinopathy,“ “adhesions,“ or “gliding,“ independently. In quite all the experimental studies, performed after surgical procedures for tendon injuries or in the treatment of chronic tendinopathies, using different hyaluronic acid compounds, positive results (reduced formation of scars and granulation tissue after tendon repair, less adhesions and gliding resistance, and improved tissue healing were observed. In a limited number of cases, hyaluronic acid has been employed in clinical practice. After flexor tendon surgery, a greater total active motion and fingers function, with an earlier return to work and daily activities, were observed. Similarly, in patients suffering from elbow, patellar, and shoulder tendons disorders, pain was reduced, and function improved. The positive effect of hyaluronic acid can be attributed to the anti-inflammatory activity, enhanced cell proliferation, and collagen deposition, besides the lubricating action on the sliding surface of the tendon.

  2. Wide-Awake Primary Flexor Tendon Repair, Tenolysis, and Tendon Transfer

    OpenAIRE

    Tang, Jin Bo

    2015-01-01

    Tendon surgery is unique because it should ensure tendon gliding after surgery. Tendon surgery now can be performed under local anesthesia without tourniquet, by injecting epinephrine mixed with lidocaine, to achieve vasoconstriction in the area of surgery. This method allows the tendon to move actively during surgery to test tendon function intraoperatively and to ensure the tendon is properly repaired before leaving the operating table. I applied this method to primary flexor tendon repair ...

  3. Gastrocnemius tendon length and strain are different when assessed using straight or curved tendon model

    OpenAIRE

    Stosic, Jelena; Finni Juutinen, Taija

    2011-01-01

    The present study investigated the effects of tendon curvature on measurements of tendon length using 3D-kinematic analysis. Curved and straight tendon models were employed for assessing medial gastrocnemius tendon length and strain during hopping (N = 8). Tendon curvature was identified using small reflective markers placed on the skin surface along the length of the tendon and a sum of vectors between the markers from the calcaneous up to the marker at the origin of tendon was calculated. T...

  4. Development of a surgically optimized graft insertion suture technique to accommodate a tissue-engineered tendon in vivo.

    Science.gov (United States)

    Sawadkar, Prasad; Alexander, Susan; Tolk, Marten; Wong, Jason; McGrouther, Duncan; Bozec, Laurent; Mudera, Vivek

    2013-10-01

    The traumatic rupture of tendons is a common clinical problem. Tendon repair is surgically challenging because the tendon often retracts, resulting in a gap between the torn end and its bony insertion. Tendon grafts are currently used to fill this deficit but are associated with potential complications relating to donor site morbidity and graft necrosis. We have developed a highly reproducible, rapid process technique to manufacture compressed cell-seeded type I collagen constructs to replace tendon grafts. However, the material properties of the engineered constructs are currently unsuitable to withstand complete load bearing in vivo. A modified suture technique has been developed to withstand physiological loading and off load the artificial construct while integration occurs. Lapine tendons were used ex vivo to test the strength of different suture techniques with different sizes of Prolene sutures and tissue-engineered collagen constructs in situ. The data were compared to standard modified Kessler suture using a standard tendon graft. Mechanical testing was carried out and a finite element analysis stress distribution model constructed using COMSOL 3.5 software. The break point for modified suture technique with a tissue-engineered scaffold was significantly higher (50.62 N) compared to a standard modified Kessler suture (12.49 N, ptechnique is suitable for testing in vivo, and this will be the next stage of our research.

  5. Novel methods for tendon investigations

    DEFF Research Database (Denmark)

    Kjær, Michael; Langberg, Henning; Bojsen-Møller, J.

    2008-01-01

    Purpose. Tendon structures have been studied for decades, but over the last decade, methodological development and renewed interest for metabolic, circulatory and tissue protein turnover in tendon tissue has resulted in a rising amount of investigations. Method. This paper will detail the various...

  6. Capacity of muscle derived stem cells and pericytes to promote tendon graft integration and ligamentization following anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Ćuti, Tomislav; Antunović, Maja; Marijanović, Inga; Ivković, Alan; Vukasović, Andreja; Matić, Igor; Pećina, Marko; Hudetz, Damir

    2017-06-01

    The aim of this study is to examine the capacity of muscle tissue preserved on hamstring tendons forming candy-stripe grafts in order to improve tendon to bone ingrowth and ligamentization. We hypothesized that muscle tissue does possess a stem cell population that could enhance the healing process of the ACL graft when preserved on the tendons. Human samples from gracilis and semitendinosus muscles were collected during ACL surgery from ten patients and from these tissue samples human muscle-derived stem cells and tendon-derived stem cells were isolated and propagated. Both stem cell populations were in-vitro differentiated into osteogenic lineage. Alkaline phosphatase activity was determined at days zero and 14 of the osteogenic induction and von Kossa staining to assess mineralization of the cultures. Total RNA was collected from osteoblast cultures and real time quantitative PCR was performed. Western-blot for osteocalcin and collagen type I followed protein isolation. Immunofluorescence double labeling of pericytes in muscle and tendon tissue was performed. Mesenchymal stem cells from muscle and tendon tissue were isolated and expanded in cell culture. More time was needed to grow the tendon derived culture compared to muscle derived culture. Muscle derived stem cells exhibited more alkaline phosphatase actvity compared to tendon derived stem cells, whereas tendon derived stem cells formed more mineralized nodules after 14 days of osteoinduction. Muscle derived stem cells exhibited higher expression levels of bone sialoprotein, and tendon derived stem cells showed higher expression of dental-matrix-protein 1 and osteocalcin. Immunofluorescent staining against pericytes indicated that they are more abundant in muscle tissue. These results indicate that muscle tissue is a better source of stem cells than tendon tissue. Achievement of this study is proof that there is vast innate capacity of muscle tissue for enhancement of bone-tendon integration and

  7. Ultrasound-guided tendon fenestration.

    Science.gov (United States)

    Chiavaras, Mary M; Jacobson, Jon A

    2013-02-01

    A potential treatment for chronic tendinosis or tendinopathy is percutaneous ultrasound-guided tendon fenestration, also termed dry needling or tenotomy. This procedure involves gently passing a needle through the abnormal tendon multiple times to change a chronic degenerative process into an acute condition that is more likely to heal. This article reviews the literature on tendon fenestration and describes the technical aspects of this procedure including postprocedural considerations. Although peer-reviewed literature on this topic is limited, studies to date have shown that ultrasound-guided tendon fenestration can improve patient symptoms. Several other percutaneous treatments for tendinopathy that include prolotherapy, autologous whole-blood injection, and autologous platelet-rich plasma injection are often performed in conjunction with fenestration. It is currently unknown if these other percutaneous procedures have any benefit over ultrasound-guided tendon fenestration alone. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Modelling the mechanics of partially mineralized collagen fibrils, fibres and tissue

    Science.gov (United States)

    Liu, Yanxin; Thomopoulos, Stavros; Chen, Changqing; Birman, Victor; Buehler, Markus J.; Genin, Guy M.

    2014-01-01

    Progressive stiffening of collagen tissue by bioapatite mineral is important physiologically, but the details of this stiffening are uncertain. Unresolved questions about the details of the accommodation of bioapatite within and upon collagen's hierarchical structure have posed a central hurdle, but recent microscopy data resolve several major questions. These data suggest how collagen accommodates bioapatite at the lowest relevant hierarchical level (collagen fibrils), and suggest several possibilities for the progressive accommodation of bioapatite at higher hierarchical length scales (fibres and tissue). We developed approximations for the stiffening of collagen across spatial hierarchies based upon these data, and connected models across hierarchies levels to estimate mineralization-dependent tissue-level mechanics. In the five possible sequences of mineralization studied, percolation of the bioapatite phase proved to be an important determinant of the degree of stiffening by bioapatite. The models were applied to study one important instance of partially mineralized tissue, which occurs at the attachment of tendon to bone. All sequences of mineralization considered reproduced experimental observations of a region of tissue between tendon and bone that is more compliant than either tendon or bone, but the size and nature of this region depended strongly upon the sequence of mineralization. These models and observations have implications for engineered tissue scaffolds at the attachment of tendon to bone, bone development and graded biomimetic attachment of dissimilar hierarchical materials in general. PMID:24352669

  9. Do cells contribute to tendon and ligament biomechanics?

    Directory of Open Access Journals (Sweden)

    Niels Hammer

    Full Text Available Acellular scaffolds are increasingly used for the surgical repair of tendon injury and ligament tears. Despite this increased use, very little data exist directly comparing acellular scaffolds and their native counterparts. Such a comparison would help establish the effectiveness of the acellularization procedure of human tissues. Furthermore, such a comparison would help estimate the influence of cells in ligament and tendon stability and give insight into the effects of acellularization on collagen.Eighteen human iliotibial tract samples were obtained from nine body donors. Nine samples were acellularized with sodium dodecyl sulphate (SDS, while nine counterparts from the same donors remained in the native condition. The ends of all samples were plastinated to minimize material slippage. Their water content was adjusted to 69%, using the osmotic stress technique to exclude water content-related alterations of the mechanical properties. Uniaxial tensile testing was performed to obtain the elastic modulus, ultimate stress and maximum strain. The effectiveness of the acellularization procedure was histologically verified by means of a DNA assay.The histology samples showed a complete removal of the cells, an extensive, yet incomplete removal of the DNA content and alterations to the extracellular collagen. Tensile properties of the tract samples such as elastic modulus and ultimate stress were unaffected by acellularization with the exception of maximum strain.The data indicate that cells influence the mechanical properties of ligaments and tendons in vitro to a negligible extent. Moreover, acellularization with SDS alters material properties to a minor extent, indicating that this method provides a biomechanical match in ligament and tendon reconstruction. However, the given protocol insufficiently removes DNA. This may increase the potential for transplant rejection when acellular tract scaffolds are used in soft tissue repair. Further research

  10. Heat Shock Protein 90 Inhibitor Decreases Collagen Synthesis of Keloid Fibroblasts and Attenuates the Extracellular Matrix on the Keloid Spheroid Model.

    Science.gov (United States)

    Lee, Won Jai; Lee, Ju Hee; Ahn, Hyo Min; Song, Seung Yong; Kim, Yong Oock; Lew, Dae Hyun; Yun, Chae-Ok

    2015-09-01

    The 90-kDa heat-shock protein (heat-shock protein 90) is an abundant cytosolic chaperone, and inhibition of heat-shock protein 90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) compromises transforming growth factor (TGF)-β-mediated transcriptional responses by enhancing TGF-β receptor I and II degradation, thus preventing Smad2/3 activation. In this study, the authors evaluated whether heat-shock protein 90 regulates TGF-β signaling in the pathogenesis and treatment of keloids. Keloid fibroblasts were treated with 17-AAG (10 μM), and mRNA levels of collagen types I and III were determined by real-time reverse- transcriptase polymerase chain reaction. Also, secreted TGF-β1 was assessed by enzyme-linked immunosorbent assay. The effect of 17-AAG on protein levels of Smad2/3 complex was determined by Western blot analysis. In addition, in 17-AAG-treated keloid spheroids, the collagen deposition and expression of major extracellular matrix proteins were investigated by means of Masson trichrome staining and immunohistochemistry. The authors found that heat-shock protein 90 is overexpressed in human keloid tissue compared with adjacent normal tissue, and 17-AAG decreased mRNA levels of type I collagen, secreted TGF-ß1, and Smad2/3 complex protein expression in keloid fibroblasts. Masson trichrome staining revealed that collagen deposition was decreased in 17-AAG-treated keloid spheroids, and immunohistochemical analysis showed that expression of collagen types I and III, elastin, and fibronectin was markedly decreased in 17-AAG-treated keloid spheroids. These results suggest that the antifibrotic action of heat-shock protein 90 inhibitors such as 17-AAG may have therapeutic effects on keloids.

  11. Tensile properties of human collagen fibrils and fascicles are insensitive to environmental salts

    DEFF Research Database (Denmark)

    Svensson, René B; Hassenkam, Tue; Grant, Colin A

    2010-01-01

    loading direction of tendon is along its longitudinal axis. Thus, in this study, we focus on the tensile mechanical properties of two hierarchical levels from human patellar tendon, namely: individual collagen fibrils and fascicles. Investigations on collagen fibrils and fascicles were made at pH 7.......4 in solutions of phosphate-buffered saline at three different concentrations as well as two HEPES buffered solutions containing NaCl or NaCl + CaCl2. An atomic force microscope technique was used for tensile testing of individual collagen fibrils. Only a slight increase in relative energy dissipation...... was observed at the highest phosphate-buffered saline concentration for both the fibrils and fascicles, indicating a stabilizing effect of ionic screening, but changes were much less than reported for radial compression. Due to the small magnitude of the effects, the tensile mechanical properties of collagen...

  12. The Collagen Family

    Science.gov (United States)

    Ricard-Blum, Sylvie

    2011-01-01

    Collagens are the most abundant proteins in mammals. The collagen family comprises 28 members that contain at least one triple-helical domain. Collagens are deposited in the extracellular matrix where most of them form supramolecular assemblies. Four collagens are type II membrane proteins that also exist in a soluble form released from the cell surface by shedding. Collagens play structural roles and contribute to mechanical properties, organization, and shape of tissues. They interact with cells via several receptor families and regulate their proliferation, migration, and differentiation. Some collagens have a restricted tissue distribution and hence specific biological functions. PMID:21421911

  13. Regulation of collagen biosynthesis by ascorbic acid: a review.

    OpenAIRE

    Pinnell, S R

    1985-01-01

    L-ascorbic acid is an essential cofactor for lysyl hydroxylase and prolyl hydroxylase, enzymes essential for collagen biosynthesis. In addition, L-ascorbic acid preferentially stimulates collagen synthesis in a manner which appears unrelated to the effect of L-ascorbic acid on hydroxylation reactions. This reaction is stereospecific and unrelated to intracellular degradation of collagen. The effect apparently occurs at a transcriptional or translational level, since L-ascorbic acid preferenti...

  14. Comparative study of laser and LED systems of low intensity applied to tendon healing

    Science.gov (United States)

    Bastos, J. L. N.; Lizarelli, R. F. Z.; Parizotto, N. A.

    2009-09-01

    The aim of this study was to compare the effects of Low-intensity Laser Therapy (LILT) and Light Emitting Diode Therapy (LEDT) of low intensity on the treatment of lesioned Achilles tendon of rats. The experimental model consisted of a partial mechanical lesion on the right Achilles tendon deep portion of 90 rats. One hour after the lesion, the injured animals received applications of laser/LED (685, 830/630, 880 nm), and the same procedure was repeated at 24-h intervals, for 10 days. The healing process and deposition of collagen were evaluated based on a polarization microscopy analysis of the alignment and organization of collagen bundles, through the birefringence (optical retardation-OR). The results showed a real efficiency of treatments based on LEDT and confirmed that LILT seems to be effective on healing process. Although absence of coherence of LED light, tendon healing treatment with this feature was satisfactory and can certainly replace treatments based on laser light applications. Applications of infrared laser at 830 nm and LED 880 nm were more efficient when the aim is a good organization, aggregation, and alignment of the collagen bundles on tendon healing. However, more research is needed for a safety and more efficient determination of a protocol with LED.

  15. Collagen fibril diameter and leather strength.

    Science.gov (United States)

    Wells, Hannah C; Edmonds, Richard L; Kirby, Nigel; Hawley, Adrian; Mudie, Stephen T; Haverkamp, Richard G

    2013-11-27

    The main structural component of leather and skin is type I collagen in the form of strong fibrils. Strength is an important property of leather, and the way in which collagen contributes to the strength is not fully understood. Synchrotron-based small angle X-ray scattering (SAXS) is used to measure the collagen fibril diameter of leather from a range of animals, including sheep and cattle, that had a range of tear strengths. SAXS data were fit to a cylinder model. The collagen fibril diameter and tear strength were found to be correlated in bovine leather (r(2) = 0.59; P = 0.009), with stronger leather having thicker fibrils. There was no correlation between orientation index, i.e., fibril alignment, and fibril diameter for this data set. Ovine leather showed no correlation between tear strength and fibril diameter, nor was there a correlation across a selection of other animal leathers. The findings presented here suggest that there may be a different structural motif in skin compared with tendon, particularly ovine skin or leather, in which the diameter of the individual fibrils contributes less to strength than fibril alignment does.

  16. Effect of androgenic-anabolic steroids and heavy strength training on patellar tendon morphological and mechanical properties.

    Science.gov (United States)

    Seynnes, Olivier R; Kamandulis, Sigitas; Kairaitis, Ramutis; Helland, Christian; Campbell, Emma-Louise; Brazaitis, Marius; Skurvydas, Albertas; Narici, Marco V

    2013-07-01

    Combined androgenic-anabolic steroids (AAS) and overloading affects tendon collagen metabolism and ultrastructure and is often associated with a higher risk of injury. The aim of this prospective study was to investigate whether such effects would be reflected in the patellar tendon properties of individuals with a history of long-term resistance training and AAS abuse (RTS group), compared with trained (RT) and untrained (CTRL) nonsteroids users. Tendon cross-sectional area (CSA), stiffness, Young's modulus, and toe limit strain were measured in vivo, from synchronized ultrasonography and dynamometry data. The patellar tendon of RT and RTS subjects was much stiffer and larger than in the CTRL group. However, stiffness and modulus were higher in the RTS group (26%, P < 0.05 and 30%, P < 0.01, respectively) than in the RT group. Conversely, tendon CSA was 15% (P < 0.05) larger in the RT group than in RTS, although differences disappeared when this variable was normalized to quadriceps maximal isometric torque. Yet maximal tendon stress was higher in RTS than in RT (15%, P < 0.05), without any statistical difference in maximal strain and toe limit strain between groups. The present lack of difference in toe limit strain does not substantiate the hypothesis of changes in collagen crimp pattern associated with AAS abuse. However, these findings indicate that tendon adaptations from years of heavy resistance training are different in AAS users, suggesting differences in collagen remodeling. Some of these adaptations (e.g., higher stress) could be linked to a higher risk of tendon injury.

  17. Effect of Aloe vera application on the content and molecular arrangement of glycosaminoglycans during calcaneal tendon healing.

    Science.gov (United States)

    Aro, Andrea Aparecida de; Esquisatto, Marcelo Augusto Marretto; Nishan, Umar; Perez, Mylena Oliveira; Rodrigues, Rodney Alexandre Ferreira; Foglio, Mary Ann; Carvalho, João Ernesto de; Gomes, Laurecir; Vidal, Benedicto De Campos; Pimentel, Edson Rosa

    2014-12-01

    Although several treatments for tendon lesions have been proposed, successful tendon repair remains a great challenge for orthopedics, especially considering the high incidence of re-rupture of injured tendons. Our aim was to evaluate the pharmacological potential of Aloe vera on the content and arrangement of glycosaminoglycans (GAGs) during tendon healing, which was based on the effectiveness of A. vera on collagen organization previously observed by our group. In rats, a partial calcaneal tendon transection was performed with subsequent topical A. vera application at the injury site. The tendons were treated with A. vera ointment for 7 days and excised on the 7(th) , 14(th) , or 21(st) day post-surgery. Control rats received ointment without A. vera. A higher content of GAGs and a lower amount of dermatan sulfate were detected in the A. vera-treated group on the 14(th) day compared with the control. Also at 14 days post-surgery, a lower dichroic ratio in toluidine blue stained sections was observed in A. vera-treated tendons compared with the control. No differences were observed in the chondroitin-6-sulfate and TGF-β1 levels between the groups, and higher amount of non-collagenous proteins was detected in the A. vera-treated group on the 21(st) day, compared with the control group. No differences were observed in the number of fibroblasts, inflammatory cells and blood vessels between the groups. The application of A. vera during tendon healing modified the arrangement of GAGs and increased the content of GAGs and non-collagenous proteins. © 2014 Wiley Periodicals, Inc.

  18. Composition and structure of porcine digital flexor tendon-bone insertion tissues.

    Science.gov (United States)

    Chandrasekaran, Sandhya; Pankow, Mark; Peters, Kara; Huang, Hsiao-Ying Shadow

    2017-11-01

    Tendon-bone insertion is a functionally graded tissue, transitioning from 200 MPa tensile modulus at the tendon end to 20 GPa tensile modulus at the bone, across just a few hundred micrometers. In this study, we examine the porcine digital flexor tendon insertion tissue to provide a quantitative description of its collagen orientation and mineral concentration by using Fast Fourier Transform (FFT) based image analysis and mass spectrometry, respectively. Histological results revealed uniformity in global collagen orientation at all depths, indicative of mechanical anisotropy, although at mid-depth, the highest fiber density, least amount of dispersion, and least cellular circularity were evident. Collagen orientation distribution obtained through 2D FFT of histological imaging data from fluorescent microscopy agreed with past measurements based on polarized light microscopy. Results revealed global fiber orientation across the tendon-bone insertion to be preserved along direction of physiologic tension. Gradation in the fiber distribution orientation index across the insertion was reflective of a decrease in anisotropy from the tendon to the bone. We provided elemental maps across the fibrocartilage for its organic and inorganic constituents through time-of-flight secondary ion mass spectrometry (TOF-SIMS). The apatite intensity distribution from the tendon to bone was shown to follow a linear trend, supporting past results based on Raman microprobe analysis. The merit of this study lies in the image-based simplified approach to fiber distribution quantification and in the high spatial resolution of the compositional analysis. In conjunction with the mechanical properties of the insertion tissue, fiber, and mineral distribution results for the insertion from this may potentially be incorporated into the development of a structural constitutive approach toward computational modeling. Characterizing the properties of the native insertion tissue would provide the

  19. Ultrasound elasticity imaging of human posterior tibial tendon

    Science.gov (United States)

    Gao, Liang

    Posterior tibial tendon dysfunction (PTTD) is a common degenerative condition leading to a severe impairment of gait. There is currently no effective method to determine whether a patient with advanced PTTD would benefit from several months of bracing and physical therapy or ultimately require surgery. Tendon degeneration is closely associated with irreversible degradation of its collagen structure, leading to changes to its mechanical properties. If these properties could be monitored in vivo, it could be used to quantify the severity of tendonosis and help determine the appropriate treatment. Ultrasound elasticity imaging (UEI) is a real-time, noninvasive technique to objectively measure mechanical properties in soft tissue. It consists of acquiring a sequence of ultrasound frames and applying speckle tracking to estimate displacement and strain at each pixel. The goals of my dissertation were to 1) use acoustic simulations to investigate the performance of UEI during tendon deformation with different geometries; 2) develop and validate UEI as a potentially noninvasive technique for quantifying tendon mechanical properties in human cadaver experiments; 3) design a platform for UEI to measure mechanical properties of the PTT in vivo and determine whether there are detectable and quantifiable differences between healthy and diseased tendons. First, ultrasound simulations of tendon deformation were performed using an acoustic modeling program. The effects of different tendon geometries (cylinder and curved cylinder) on the performance of UEI were investigated. Modeling results indicated that UEI accurately estimated the strain in the cylinder geometry, but underestimated in the curved cylinder. The simulation also predicted that the out-of-the-plane motion of the PTT would cause a non-uniform strain pattern within incompressible homogeneous isotropic material. However, to average within a small region of interest determined by principal component analysis (PCA

  20. Effects of fish collagen peptides on collagen post-translational modifications and mineralization in an osteoblastic cell culture system

    OpenAIRE

    Yamada, Shizuka; Nagaoka, Hideaki; Terajima, Masahiko; Tsuda, Nobuaki; Hayashi, Yoshihiko; Yamauchi, Mitsuo

    2013-01-01

    Collagen is one of the most widely used biomaterials for tissue engineering and regenerative medicine. Fish collagen peptides (FCP) have been used as a dietary supplement, but their effects on the cellular function are still poorly understood. The objective of this study was to investigate the effects of FCP on collagen synthesis, quality and mineralization using an osteoblastic MC3T3-E1 cell culture system. Cells treated with FCP significantly upregulated the gene expression of several colla...

  1. Lineage tracing of resident tendon progenitor cells during growth and natural healing.

    Directory of Open Access Journals (Sweden)

    Nathaniel A Dyment

    Full Text Available Unlike during embryogenesis, the identity of tissue resident progenitor cells that contribute to postnatal tendon growth and natural healing is poorly characterized. Therefore, we utilized 1 an inducible Cre driven by alpha smooth muscle actin (SMACreERT2, that identifies mesenchymal progenitors, 2 a constitutively active Cre driven by growth and differentiation factor 5 (GDF5Cre, a critical regulator of joint condensation, in combination with 3 an Ai9 Cre reporter to permanently label SMA9 and GDF5-9 populations and their progeny. In growing mice, SMA9+ cells were found in peritendinous structures and scleraxis-positive (ScxGFP+ cells within the tendon midsubstance and myotendinous junction. The progenitors within the tendon midsubstance were transiently labeled as they displayed a 4-fold expansion from day 2 to day 21 but reduced to baseline levels by day 70. SMA9+ cells were not found within tendon entheses or ligaments in the knee, suggesting a different origin. In contrast to the SMA9 population, GDF5-9+ cells extended from the bone through the enthesis and into a portion of the tendon midsubstance. GDF5-9+ cells were also found throughout the length of the ligaments, indicating a significant variation in the progenitors that contribute to tendons and ligaments. Following tendon injury, SMA9+ paratenon cells were the main contributors to the healing response. SMA9+ cells extended over the defect space at 1 week and differentiated into ScxGFP+ cells at 2 weeks, which coincided with increased collagen signal in the paratenon bridge. Thus, SMA9-labeled cells represent a unique progenitor source that contributes to the tendon midsubstance, paratenon, and myotendinous junction during growth and natural healing, while GDF5 progenitors contribute to tendon enthesis and ligament development. Understanding the mechanisms that regulate the expansion and differentiation of these progenitors may prove crucial to improving future repair strategies.

  2. Hemodynamic study for the healing process of ruptured achilles tendon by dynamic MRI

    Energy Technology Data Exchange (ETDEWEB)

    Mizuno, Toshiyuki [Hyogo Rehabilitation Center (Japan); Hamanishi, Hiroji; Nishikawa, Tetsuo; Mizuno, Kosaku

    2000-12-01

    Dynamic MR imaging with a combination of fast MR imaging technique and intravenous bolus administration of Gd-DTPA is a useful method to evaluate the vascularity of the soft tissue. By using this technique, we evaluated the healing processes of ruptured Achilles tendon. Eighteen patients who underwent percutaneous suture of the ruptured Achilles tendon were examined monthly by dynamic MRI in their course of healing. We evaluated time intensity curve obtained from each data of dynamic MRI. Time intensity curve showed slow fill in-slow wash out pattern 4 weeks after operation. Eight weeks after operation, the time course of the fill in-wash out changed to be shorter. Rapid fill in-rapid wash out pattern was observed about 12 weeks after surgery. After that period, time intensity curve tended to change into non-fitting pattern. (normal pattern) Eight functional parameters were obtained from time-intensity curve. We analyzed which parameters are useful for evaluation of tendon healing. In addition, we studied the healing processes of rabbit Achilles tendon following surgical incision. Twelve rabbits underwent tenotomy of Achilles tendon. The tendons excised at 1, 2, 4, 6, 8, 10, 12 weeks after operation were examined using microangiography and a light microscope. Four weeks after tenotomy, many capillary vessels filled with Gd-DTPA were observed in the ruptured area. About 10 weeks after operation, the capillary vessels decreased and collageneous fibers were arranged along the long axis of the tendon. This term would be thought to correspond to the condition about 12-14 weeks after surgery in clinical cases. From this study, dynamic MRI is thought to be useful method to know the hemodynamic conditions of the healing tendons. Especially, four parameters-Mean Transit Time, Corrected Transit Time, Time to Peak, Inflection Width, -seemed to have absolute value and be useful for the quantitative evaluation of the healing processes in human Achilles tendon. (author)

  3. Collagen Gel Contraction by Fibroblasts: The Role of Myosin 2 and Gravity Effects

    Science.gov (United States)

    Johnson-Wint, Barbara P.; Malouvier, Alexandre; Holton, Emily

    1996-01-01

    Several lines of evidence suggest that collagen organization by connective tissue cells is sensitive to force. For instance, in flight experiments on rats the collagen fibrils which were produced under weightlessness and which were immediately next to the tendon fibroblasts were shown to be oriented randomly around the cells while the older fibrils right next to these and which were produced under 1 G, were highly organized.

  4. High-intensity focused ultrasound ablation of ex vivo bovine achilles tendon.

    Science.gov (United States)

    Muratore, Robert; Akabas, Tal; Muratore, Isabella B

    2008-12-01

    Small tears in tendons are a common occurrence in athletes and others involved in strenuous physical activity. Natural healing in damaged tendons can result in disordered regrowth of the underlying collagen matrix of the tendon. These disordered regions are weaker than surrounding ordered regions of normal tendon and are prone to re-injury. Multiple cycles of injury and repair can lead to chronic tendinosis. Current treatment options either are invasive or are relatively ineffective in tendinosis without calcifications. High-intensity focused ultrasound (HIFU) has the potential to treat tendinosis noninvasively. HIFU ablation of tendons is based on a currently-used surgical analog, viz., needle tenotomy. This study tested the ability of HIFU beams to ablate bovine tendons ex vivo. Two ex vivo animal models were employed: a bare bovine Achilles tendon (deep digital flexor) on an acoustically absorbent rubber pad, and a layered model (chicken breast proximal, bovine Achilles tendon central and a glass plate distal to the transducer). The bare-tendon model enables examination of lesion formation under simple, ideal conditions; the layered model enables detection of possible damage to intervening soft tissue and consideration of the possibly confounding effects of distal bone. In both models, the tissues were degassed in normal phosphate-buffered saline. The bare tendon was brought to 23 degrees C or 37 degrees C before insonification; the layered model was brought to 37 degrees C before insonification. The annular array therapy transducer had an outer diameter of 33 mm, a focal length of 35 mm and a 14-mm diameter central hole to admit a confocal diagnostic transducer. The therapy transducer was excited with a continuous sinusoidal wave at 5.25 MHz to produce nominal in situ intensities from 0.23-2.6 kW/cm(2). Insonification times varied from 2-10 s. The focus was set over the range from the proximal tendon surface to 7 mm deep. The angle of incidence ranged from 0

  5. Incorporation of a Decorin Biomimetic Enhances the Mechanical Properties of Electrochemically Aligned Collagen Threads

    Science.gov (United States)

    Kishore, Vipuil; Paderi, John E.; Akkus, Anna; Smith, Katie M.; Balachandran, Dave; Beaudoin, Stephen; Panitch, Alyssa; Akkus, Ozan

    2011-01-01

    Orientational anisotropy of collagen molecules is integral for the mechanical strength of collagen-rich tissues. We have previously reported a novel methodology to synthesize highly oriented electrochemically aligned collagen (ELAC) threads with mechanical properties converging upon those of native tendon. Decorin, a small leucine rich proteoglycan (SLRP), binds to fibrillar collagen and has been suggested to enhance the mechanical properties of tendon. Based on the structure of natural decorin, we have previously designed and synthesized a peptidoglycan (DS-SILY) that mimics decorin both structurally and functionally. In this study, we investigated the effect of the incorporation of DS-SILY on the mechanical properties and structural organization of ELAC threads. The results indicated that the addition of DS-SILY at a molar ratio of 30:1 (Collagen:DS-SILY) significantly enhanced the ultimate stress and ultimate strain of the ELAC threads. Furthermore, differential scanning calorimetry revealed that the addition of DS-SILY at a molar ratio of 30:1 resulted in a more thermally stable collagen structure. However, addition of DS-SILY at a higher concentration (10:1 Collagen:DS-SILY) yielded weaker threads with mechanical properties comparable to collagen control threads. Transmission emission microscopy revealed that the addition of DS-SILY at a higher concentration (10:1) resulted in pronounced aggregation of collagen fibrils. More importantly, these aggregates were not aligned along the long axis of the ELAC thereby compromising on the overall tensile properties of the material. We conclude that incorporation of an optimal amount of DS-SILY is a promising approach to synthesize mechanically competent collagen based biomaterials for tendon tissue engineering applications. PMID:21356334

  6. Collagen vascular disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on this page, ... previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many specific conditions ...

  7. Rectus Femoris Tendon Calcification

    Science.gov (United States)

    Zini, Raul; Panascì, Manlio; Papalia, Rocco; Franceschi, Francesco; Vasta, Sebastiano; Denaro, Vincenzo

    2014-01-01

    Background: Since it was developed, hip arthroscopy has become the favored treatment for femoroacetabular impingement. Due to recent considerable improvements, the indications for this technique have been widely extended. Injuries of the rectus femoris tendon origin, after an acute phase, could result in a chronic tendinopathy with calcium hydroxyapatite crystal deposition, leading to pain and loss of function. Traditionally, this condition is addressed by local injection of anesthetic and corticosteroids or, when conservative measures fail, by open excision of the calcific lesion by an anterior approach. Purpose: To assess whether arthroscopic excision of calcification of the proximal rectus is a safe and effective treatment. Study Design: Case series; Level of evidence, 4. Methods: Outcomes were studied from 6 top amateur athletes (age range, 30-43 years; mean, 32.6 years) affected by calcification of the proximal rectus who underwent arthroscopic excision of the calcification. Patients were preoperatively assessed radiographically, and diagnosis was confirmed by a 3-dimensional computed tomography scan. To evaluate the outcome, standardized hip rating scores were used pre- and postoperatively (at 6 and 12 months): the Hip disability and Osteoarthritis Outcome Score, Oxford Hip Score, and Modified Harris Hip Score. Moreover, visual analog scales (VAS) for pain, sport activity level (SAL), and activities of daily living (ADL) were also used. Results: One year after surgery, all patients reported satisfactory outcomes, with 3 of 6 rating their return-to-sport level as high as preinjury level, and the remaining 3 with a percentage higher than 80%. Five patients ranked their ability to carry on daily activities at 100%. Statistical analysis showed significant improvement of the Oxford Hip Score, the Modified Harris Hip Score, and all 3 VAS subscales (pain, SAL, and ADL) from pre- to latest postoperative assessment (P < .05). Conclusion: Arthroscopic excision of

  8. Biceps Tendon Rupture

    Directory of Open Access Journals (Sweden)

    Daniel M Polvino

    2018-01-01

    Full Text Available History of present illness: A 55-year-old male presented to the emergency department with a chief complaint of right arm pain. Five days prior to arrival, he attempted to lift himself up on his van and experienced what he described as a “rubber band snapping” in his right arm. He reported severe pain at the time that persisted but lessened in severity. Additionally, he reported increasing bruising over the proximal right arm. He had no history of prior right arm or shoulder injury. Significant findings: Physical exam was significant for ecchymosis and mild swelling of the right bicep. When the right arm was flexed at the elbow, a prominent mass was visible and palpable over the right bicep. Right upper extremity strength was 4/5 with flexion at the elbow. Discussion: The biceps brachii muscle is comprised of a long and short head, which share a common attachment at the bicipital tuberosity on the radius. The short head originates from the coracoid process of the scapula and the long head originates from the supraglenoid tubercle.1 Biceps tendon rupture has been found to occur at a rate of 0.53/100,000 over five years, and is three times more likely to occur in men than women.2 Risk factors for biceps tendon rupture include male sex, old age, increased body mass index, smoking, and pre-existing shoulder pathology.3,4 Diagnosis of biceps tendon rupture is typically a clinical diagnosis utilizing inspection and palpation as well as special testing such as the Speed’s and/or Yergason’s tests. Ultrasound may be used to aid in diagnosis; in full-thickness tears, ultrasound was found to have a sensitivity of 88% and a specificity of 98%. However, in partial thickness tears ultrasound has a sensitivity of 27% and a specificity of 100%.5 Often considered the gold standard in diagnosis, MRI has been found to have a sensitivity of only 67% and specificity of 98% in detecting complete tears6. Treatment initially consists of rest, ice, compression

  9. [Pathophysiology of overuse tendon injury].

    Science.gov (United States)

    Kannus, P; Paavola, M; Paakkala, T; Parkkari, J; Järvinen, T; Järvinen, M

    2002-10-01

    Overuse tendon injury is one of the most common injuries in sports. The etiology as well as the pathophysiological mechanisms leading to tendinopathy are of crucial medical importance. At the moment intrinsic and extrinsic factors are assumed as mechanisms of overuse tendon injury. Except for the acute, extrinsic trauma, the chronic overuse tendon injury is a multifactorial process. There are many other factors, such as local hypoxia, less of nutrition, impaired metabolism and local inflammatory that may also contribute to the development of tissue damage. The exact interaction of these factors cannot be explained entirely at the moment. Further studies will be necessary in order to get more information.

  10. Experimental diabetes induces structural, inflammatory and vascular changes of Achilles tendons.

    Directory of Open Access Journals (Sweden)

    Rodrigo R de Oliveira

    Full Text Available This study aims to demonstrate how the state of chronic hyperglycemia from experimental Diabetes Mellitus can influence the homeostatic imbalance of tendons and, consequently, lead to the characteristics of tendinopathy. Twenty animals were randomly divided into two experimental groups: control group, consisting of healthy rats and diabetic group constituted by rats induced to Diabetes Mellitus I. After twenty-four days of the induction of Diabetes type I, the Achilles tendon were removed for morphological evaluation, cellularity, number and cross-sectional area of blood vessel, immunohistochemistry for Collagen type I, VEGF and NF-κB nuclear localization sequence (NLS and nitrate and nitrite level. The Achilles tendon thickness (µm/100g of diabetic animals was significantly increased and, similarly, an increase was observed in the density of fibrocytes and mast cells in the tendons of the diabetic group. The average number of blood vessels per field, in peritendinous tissue, was statistically higher in the diabetic group 3.39 (2.98 vessels/field when compared to the control group 0.89 (1.68 vessels/field p = 0.001 and in the intratendinous region, it was observed that blood vessels were extremely rare in the control group 0.035 (0.18 vessels/field and were often present in the tendons of the diabetic group 0.89 (0.99 vessels/field. The immunohistochemistry analysis identified higher density of type 1 collagen and increased expression of VEGF as well as increased immunostaining for NFκB p50 NLS in the nucleus in Achilles tendon of the diabetic group when compared to the control group. Higher levels of nitrite/nitrate were observed in the experimental group induced to diabetes. We conclude that experimental DM induces notable structural, inflammatory and vascular changes in the Achilles tendon which are compatible with the process of chronic tendinopathy.

  11. Ultrasonographic assessment of flexor tendon mobilization: Effect of different protocols on tendon excursion

    NARCIS (Netherlands)

    J.-W.H. Korstanje (Jan-Wiebe); J. Soeters (Johannes); A.R. Schreuders (Ton); P.C. Amadio (Peter ); S.E.R. Hovius (Steven); H.J. Stam (Henk); R.W. Selles (Ruud)

    2012-01-01

    textabstractBackground: Different mobilization protocols have been proposed for rehabilitation after hand flexor tendon repair to provide tendon excursion sufficient to prevent adhesions. Several cadaver studies have shown that the position of the neighboring fingers influences tendon excursions of

  12. Synthesis and super-swelling behavior of a novel low salt-sensitive protein-based superabsorbent hydrogel: collagen-g-poly(AMPS)

    OpenAIRE

    Sadeghi, Mohammad; Hosseinzadeh, Hossein

    2014-01-01

    Superabsorbent polymers are obtained by the graft copolymerization of 2-acrylamido-2-methylpropanesul- fonic acid (AMPS) monomer onto collagen, using ammonium persulfate as a free radical initiator in the presence of methylene bisacrylamide as a crosslinker. Infrared spectroscopy and TGA thermal analysis were carried out to confirm the chemical structure of the hydrogel. Moreover, morphology of the samples was examined by scanning electron microscopy (SEM). The effect of reaction var...

  13. Piezoelectric Collagen Hydrogels

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Piezoelectric Collagen Hydrogels. Stress-induced potential in bone is produced by shear piezoelectricity in collagen fibers and streaming potential in canaliculae. The growth of bone is regulated to best resist external force. Piezo electrical property of collagen has ...

  14. Achilles tendon reattachment after surgical treatment of insertional tendinosis using the suture bridge technique: a case series.

    Science.gov (United States)

    Witt, Bryan L; Hyer, Christopher F

    2012-01-01

    Achilles tendinopathy is a clinical diagnosis characterized as a triad of symptoms including pain, swelling, and impaired performance of the diseased tendon. Achilles tendinopathy is divided into Achilles tendonitis and tendinosis based on histopathological examination. Achilles tendinosis is viewed microscopically as disorganized collagen, abnormal neovascularization, necrosis, and mucoid degeneration. Insertional Achilles tendinosis is a degenerative process of the tendon at the junction of the tendon and calcaneus. This disease is initially treated conservatively with activity modification, custom orthotic devices, heel lifts, and immobilization. After 3 to 6 months of conservative therapy has failed to alleviate symptoms, surgical management is indicated. Surgical management of insertional Achilles tendinosis includes Achilles tendon debridement, calcaneal exostosis ostectomy, and retrocalcaneal bursa excision. In this case series, we present 4 patients who underwent surgical management of insertional Achilles tendinosis with complete tendon detachment. All patients underwent reattachment of the Achilles tendon with the suture bridge technique. The Arthrex SutureBridge(®) (Arthrex, Inc., Naples, FL) device uses a series of 4 suture anchors and FiberWire(®) (Arthrex Inc.) to reattach the Achilles tendon to its calcaneal insertion. This hourglass pattern of FiberWire(®) provides a greater area of tendon compression, consequently allowing greater stability and possible earlier return to weightbearing activities. The patients were followed up for approximately 2 years' duration. There were no intraoperative or postoperative complications. At final follow-up there was no evidence of Achilles tendon ruptures or device failures. All patients were able to return to their activities of daily living without the use of assistive devices. The patients' average visual analog pain scale was 1 (range 0 to 4), and their average foot functional index score was 3.41 (range 0

  15. Tendon exhibits complex poroelastic behavior at the nanoscale as revealed by high-frequency AFM-based rheology.

    Science.gov (United States)

    Connizzo, Brianne K; Grodzinsky, Alan J

    2017-03-21

    Tendons transmit load from muscle to bone by utilizing their unique static and viscoelastic tensile properties. These properties are highly dependent on the composition and structure of the tissue matrix, including the collagen I hierarchy, proteoglycans, and water. While the role of matrix constituents in the tensile response has been studied, their role in compression, particularly in matrix pressurization via regulation of fluid flow, is not well understood. Injured or diseased tendons and tendon regions that naturally experience compression are known to have alterations in glycosaminoglycan content, which could modulate fluid flow and ultimately mechanical function. While recent theoretical studies have predicted tendon mechanics using poroelastic theory, no experimental data have directly demonstrated such behavior. In this study, we use high-bandwidth AFM-based rheology to determine the dynamic response of tendons to compressive loading at the nanoscale and to determine the presence of poroelastic behavior. Tendons are found to have significant characteristic dynamic relaxation behavior occurring at both low and high frequencies. Classic poroelastic behavior is observed, although we hypothesize that the full dynamic response is caused by a combination of flow-dependent poroelasticity as well as flow-independent viscoelasticity. Tendons also demonstrate regional dependence in their dynamic response, particularly near the junction of tendon and bone, suggesting that the structural and compositional heterogeneity in tendon may be responsible for regional poroelastic behavior. Overall, these experiments provide the foundation for understanding fluid-flow-dependent poroelastic mechanics of tendon, and the methodology is valuable for assessing changes in tendon matrix compressive behavior at the nanoscale. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Firm anchoring between a calcium phosphate-hybridized tendon and bone for anterior cruciate ligament reconstruction in a goat model

    Energy Technology Data Exchange (ETDEWEB)

    Mutsuzaki, Hirotaka [Department of Orthopaedic Surgery, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Sakane, Masataka; Ochiai, Naoyuki [Department of Orthopaedic Surgery, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Hattori, Shinya; Kobayashi, Hisatoshi, E-mail: sakane-m@md.tsukuba.ac.j [Biomaterial Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan)

    2009-08-15

    Using an alternative soaking process improved the tendon-bone attachment for a calcium phosphate (CaP)-hybridized tendon graft. We characterized the deposited CaP on and in tendons and analyzed the histology and mechanical properties of the tendon-bone interface in anterior cruciate ligament (ACL) reconstruction in goats. The tendon grafts to be implanted were soaked ten times alternately in a Ca-containing solution and a PO{sub 4}-containing solution for 30 s each. Needlelike CaP nanocrystals including low-crystalline apatite were deposited on and between collagen fibrils from the surface to a depth of 200{mu}m inside the tendon. The structure resembles the extracellular matrix of bone. In animal experiments, the CaP-hybridized tendon directly bonded with newly formed bone at 6 weeks (n = 3), while fibrous bonding was observed in the control (n = 3). The ultimate failure load was not statistically different between the CaP (n = 7) and control (n = 7). However, in the failure mode, all the tendon-bone interfaces were intact in the CaP group, while three of seven specimens were pulled out from bone tunnels in the control. The result suggested that the strength of the tendon-bone interface in the CaP group is superior to that in the control group. Clinically, firm tendon-bone anchoring may lead to good results without the knee instability associated with the loosening of the bone-tendon junction in ACL reconstruction.

  17. Effect of alpine skiing training on tendon mechanical properties in older men and women.

    Science.gov (United States)

    Seynnes, O R; Koesters, A; Gimpl, M; Reifberger, A; Niederseer, D; Niebauer, J; Pirich, C; Müller, E; Narici, M V

    2011-08-01

    Strain is one of the parameters determining tendon adaptation to mechanical stimuli. The aim of this study was to test whether the patellar tendon strain induced during recreational alpine skiing would affect tendon mechanical properties in older individuals. Twenty-two older males and females (67 ± 2 years) were assigned to a 12-week guided skiing programme (IG) and 20 aged-matched volunteers served as controls (CG). Patellar tendon mechanical properties and cross-sectional area (CSA) were measured before and after training, with combined dynamometry and ultrasonography scanning. None of the variables changed significantly in the CG after training. In the IG, tendon stiffness and Young's modulus were increased (respectively, 14% and 12%, Palpine skiing is sufficient to elicit adaptive changes in patellar tendon mechanical and material properties in older subjects. Furthermore, the present sex-specific adaptations are consistent with previous reports of lower collagen metabolic responsiveness in women and may be underpinned by anthropometric and metabolic differences. © 2011 John Wiley & Sons A/S.

  18. Effect of the Position of Immobilization Upon the Tensile Properties in Injured Achilles Tendon of Rat

    Science.gov (United States)

    Min, Yong; Kwon, Young-Bae; Lee, Min-Ho

    2013-01-01

    Objective To examine the effect of the posture of immobilization upon the tensile properties in injured Achilles tendon of rat for an initial period of immobilization. Methods Forty-two Sprague-Dawley rats were used in the present study. Eighteen rats received a total tenotomy of the right Achilles tendon to mimic total rupture and were divided into three groups comprising of 6 rats each. Ankles of group A were immobilized at 60° of plantarflexion. Ankles of group B were immobilized at neutral position. Whereas, those of group C were immobilized at 60° of dorsiflexion. Other 18 rats received hemitenotomy to mimic partial rupture and were divided into three groups. The remaining 6 rats were kept free as control. After 14 days, we dissected the tendons and analyzed maximum force, stiffness, and energy uptake during pulling of the tendons until they ruptured. The tendons of 6 rats in each group and control were reserved for histology. Picrosirius staining was done for the analysis of collagen organization. Results In total tenotomy, tensile properties were significantly different between the control and the intervention groups (p0.05). In partial tenotomy, tensile properties were significantly different between the control and the intervention groups (pdorsiflexion posture were higher than the ones for plantarflexion. Conclusion Dorsiflexion posture in partial ruptured Achilles tendon showed better functional recovery than other immobilized postures. In total ruptured case, the tensile properties showed increasing tendency in dorsiflexion posture. PMID:23525566

  19. Expression of extracellular matrix components and related growth factors in human tendon and muscle after acute exercise

    DEFF Research Database (Denmark)

    Heinemeier, K M; Bjerrum, S S; Schjerling, P

    2013-01-01

    the patellar tendon and vastus lateralis muscle of each leg at 2 (n = 10), 6 (n = 11), or 26 h (n = 10) after exercise. Levels of messenger ribonucleic acid mRNA for collagens, noncollagenous matrix proteins, and growth factors were measured with real-time reverse transcription polymerase chain reaction...

  20. Nonsurgical treatment and early return to activity leads to improved Achilles tendon fatigue mechanics and functional outcomes during early healing in an animal model.

    Science.gov (United States)

    Freedman, Benjamin R; Gordon, Joshua A; Bhatt, Pankti R; Pardes, Adam M; Thomas, Stephen J; Sarver, Joseph J; Riggin, Corinne N; Tucker, Jennica J; Williams, Alexis W; Zanes, Robert C; Hast, Michael W; Farber, Daniel C; Silbernagel, Karin G; Soslowsky, Louis J

    2016-12-01

    Achilles tendon ruptures are common and devastating injuries; however, an optimized treatment and rehabilitation protocol has yet to be defined. Therefore, the objective of this study was to investigate the effects of surgical repair and return to activity on joint function and Achilles tendon properties after 3 weeks of healing. Sprague-Dawley rats (N = 100) received unilateral blunt transection of their Achilles tendon. Animals were then randomized into repaired or non-repaired treatments, and further randomized into groups that returned to activity after 1 week (RTA1) or after 3 weeks (RTA3) of limb casting in plantarflexion. Limb function, passive joint mechanics, and tendon properties (mechanical, organizational using high frequency ultrasound, histological, and compositional) were evaluated. Results showed that both treatment and return to activity collectively affected limb function, passive joint mechanics, and tendon properties. Functionally, RTA1 animals had increased dorsiflexion ROM and weight bearing of the injured limb compared to RTA3 animals 3-weeks post-injury. Such functional improvements in RTA1 tendons were evidenced in their mechanical fatigue properties and increased cross sectional area compared to RTA3 tendons. When RTA1 was coupled with nonsurgical treatment, superior fatigue properties were achieved compared to repaired tendons. No differences in cell shape, cellularity, GAG, collagen type I, or TGF-β staining were identified between groups, but collagen type III was elevated in RTA3 repaired tendons. The larger tissue area and increased fatigue resistance created in RTA1 tendons may prove critical for optimized outcomes in early Achilles tendon healing following complete rupture. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2172-2180, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. Exercise-dependent IGF-I, IGFBPs, and type I collagen changes in human peritendinous connective tissue determined by microdialysis

    DEFF Research Database (Denmark)

    Olesen, Jens L; Heinemeier, Katja M; Gemmer, Carsten

    2007-01-01

    and exercise groups after 48 h (P human peritendinous tissue in response to prolonged mechanical loading with part of the increase due to trauma from the sampling......Microdialysis studies indicate that mechanical loading of human tendon during exercise elevates type I collagen production in tendon. However, the possibility that the insertion of microdialysis fibers per se may increase the local collagen production due to trauma has not been explored. Insulin......-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen] were measured by microdialysis in peritendinous tissue of the human Achilles tendon in an exercise group (performing a 36-km run, n = 6) and a control group (no intervention, n = 6). An increase in local PICP concentration was seen in both...

  2. Histologic pattern of biomechanic properties of the carbon fiber-augmented ligament tendon. A laboratory and clinical study.

    Science.gov (United States)

    Mendes, D G; Iusim, M; Angel, D; Rotem, A; Roffman, M; Grishkan, A; Mordohohovich, D; Boss, J

    1985-06-01

    Implantation of carbon fiber tow (CFT) for ligament and tendon augmentation was investigated in ten dogs and 45 patients. CFT produced a new structure with a remarkably consistent structural pattern. The basic pattern of the CFT-augmented unit consisted of a core of carbon fiber surround by concentric layers of fibroblasts and collagen fibers. This unit structure was developed from continuous irritation of physical structure of the carbon fiber. In dogs, ultimate tensile strength of the augmented tendon one year after surgery averaged 88% of natural tendon. Digestion of the connective tissue component of the CFT unit exposed the original carbon fiber tow. The connective tissue-free CFT maintained its original tensile strength. The continuous production of collagenous tissue surrounding carbon fibers produced a ligamentous structure that was physiologically compatible and biomechanically sufficient.

  3. The tendon approximator device in traumatic injuries.

    Science.gov (United States)

    Forootan, Kamal S; Karimi, Hamid; Forootan, Nazilla-Sadat S

    2015-01-01

    Precise and tension-free approximation of two tendon endings is the key predictor of outcomes following tendon lacerations and repairs. We evaluate the efficacy of a new tendon approximator device in tendon laceration repairs. In a comparative study, we used our new tendon approximator device in 99 consecutive patients with laceration of 266 tendons who attend a university hospital and evaluated the operative time to repair the tendons, surgeons' satisfaction as well as patient's outcomes in a long-term follow-up. Data were compared with the data of control patients undergoing tendon repair by conventional method. Totally 266 tendons were repaired by approximator device and 199 tendons by conventional technique. 78.7% of patients in first group were male and 21.2% were female. In approximator group 38% of patients had secondary repair of cut tendons and 62% had primary repair. Patients were followed for a mean period of 3years (14-60 months). Time required for repair of each tendon was significantly reduced with the approximator device (2 min vs. 5.5 min, ptendon repair were identical in the two groups and were not significantly different. 1% of tendons in group A and 1.2% in group B had rupture that was not significantly different. The new nerve approximator device is cheap, feasible to use and reduces the time of tendon repair with sustained outcomes comparable to the conventional methods.

  4. Therapeutic Mechanisms of Human Adipose-Derived Mesenchymal Stem Cells in a Rat Tendon Injury Model.

    Science.gov (United States)

    Lee, Sang Yoon; Kwon, Bomi; Lee, Kyoungbun; Son, Young Hoon; Chung, Sun G

    2017-05-01

    Although survival of transplanted stem cells in vivo and differentiation of stem cells into tenocytes in vitro have been reported, there have been no in vivo studies demonstrating that mesenchymal stem cells (MSCs) could secrete their own proteins as differentiated tenogenic cells. Purpose/Hypothesis: Using a xenogeneic MSC transplantation model, we aimed to investigate whether MSCs could differentiate into the tenogenic lineage and secrete their own proteins. The hypothesis was that human MSCs would differentiate into the human tenogenic lineage and the cells would be able to secrete human-specific proteins in a rat tendon injury model. Controlled laboratory study. The Achilles tendons of 57 Sprague Dawley rats received full-thickness rectangular defects. After the modeling, the defective tendons were randomly assigned to 3 groups: (1) cell group, implantation with human adipose-derived mesenchymal stem cells (hASCs) and fibrin glue (106 cells in 60 μL); (2) fibrin group, implantation with fibrin glue and same volume of cell media; and (3) sham group, identical surgical procedure without any treatment. Gross observation and biomechanical, histopathological, immunohistochemistry, and Western blot analyses were performed at 2 and 4 weeks after modeling. hASCs implanted into the defective rat tendons were viable for 4 weeks as detected by immunofluorescence staining. Tendons treated with hASCs showed better gross morphological and biomechanical recovery than those in the fibrin and sham groups. Furthermore, the expression of both human-specific collagen type I and tenascin-C was significantly higher in the cell group than in the other 2 groups. Transplantation of hASCs enhanced rat tendon healing biomechanically. hASCs implanted into the rat tendon defect model survived for at least 4 weeks and secreted human-specific collagen type I and tenascin-C. These findings suggest that transplanted MSCs may be able to differentiate into the tenogenic lineage and contribute

  5. On the synthesis of tailored biomimetic hydroxyapatite nanoplates through a bioinspired approach in the presence of collagen or chitosan and L-arginine

    Energy Technology Data Exchange (ETDEWEB)

    Tsetsekou, A., E-mail: athtse@metal.ntua.gr; Brasinika, D.; Vaou, V.; Chatzitheodoridis, E.

    2014-10-01

    Controlling the structure of hydroxyapatite nanocrystals is vital for acquiring a consistent product. In an effort to synthesize crystals mimicking the morphology of natural bone's apatite, a bioinspired process was developed based on the use of a natural biomacromolecule, collagen or chitosan, in conjunction with L-arginine to direct the formation of hydroxyapatite from H{sub 3}PO{sub 4} and Ca(OH){sub 2}. Different cases were investigated by employing various concentrations of the precursors and two molar ratios of Ca/P 1/1 and 10/6. The reaction was carried out at basic pH conditions and at biomimetic temperature (40 °C). The resulting aqueous suspensions were characterized in terms of their rheological behavior, whereas the derived powders were fully evaluated by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction analysis and Raman spectroscopy. The analysis showed that in all cases, the only phase detected was hydroxyapatite of a plate-like morphology very similar to that of natural apatite. The homogeneity of the morphology and the crystal size distribution depend on the precursors' final concentration with the mean size ranging from 5 nm up to 20 nm. The powder that demonstrated the best characteristics in terms of homogeneity was that produced in the presence of collagen for molar ratio of Ca/P 1/1. - Highlights: • Hydroxyapatite nanoplates similar to those of bone's apatite were developed. • A novel approach simulating the biomineralization environment was developed. • L-Arginine was combined with collagen or chitosan to direct HAp nucleation. • Depending on reaction conditions a very homogeneous nanostructure is attained.

  6. On the fail-safe design of tendon-driven manipulators with redundant tendons

    Energy Technology Data Exchange (ETDEWEB)

    Sheu, Jinn Biau; Liu, Tyng; Lee, Jyh Jone [National Taiwan University, Taipei (China)

    2012-06-15

    A tendon-driven manipulator having redundant tendons may possess more flexibility in operation, such as optimizing the performance of tendons, reducing the burden of each tendon, and providing fail-safe features. The purpose of this paper is to investigate the design of tendon-driven manipulators with a fail-safe feature, that is, to synthesize a system that may still remain controllable as any of the tendons have broken down or malfunctioned. Characteristics of tendon-driven manipulators are briefly discussed. Criteria for tendon-driven manipulators with redundant tendons and fail-safe feature are then established. Subsequently, constraints for such system are derived from the structure of tendon-driven manipulator. Associated with the criteria, manipulators can remain controllable when any of the tendons fails to function. Finally, a geometric method for determining the structure is developed. Examples of two-DOF and three-DOF tendondriven manipulators are demonstrated.

  7. Functional assessment of gap junctions in monolayer and three-dimensional cultures of human tendon cells using fluorescence recovery after photobleaching

    OpenAIRE

    Kuzma-Kuzniarska, Maria; Yapp, Clarence; Pearson-Jones, Thomas W.; Jones, Andrew K; Hulley, Philippa A.

    2014-01-01

    Gap junction-mediated intercellular communication influences a variety of cellular activities. In tendons, gap junctions modulate collagen production, are involved in strain-induced cell death, and are involved in the response to mechanical stimulation. The aim of the present study was to investigate gap junction-mediated intercellular communication in healthy human tendon-derived cells using fluorescence recovery after photobleaching (FRAP). The FRAP is a noninvasive technique that allows qu...

  8. Radioprotection of tendon tissue via crosslinking and free radical scavenging.

    Science.gov (United States)

    Seto, Aaron; Gatt, Charles J; Dunn, Michael G

    2008-08-01

    Ionizing radiation could supplement tissue bank screening to further reduce the probability of diseases transmitted by allografts if denaturation effects can be minimized. It is important, however, such sterilization procedures be nondetrimental to tissues. We compared crosslinking and free radical scavenging potential methods to accomplish this task in tendon tissue. In addition, two forms of ionizing irradiation, gamma and electron beam (e-beam), were also compared. Crosslinkers included 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and glucose, which were used to add exogenous crosslinks to collagen. Free radical scavengers included mannitol, ascorbate, and riboflavin. Radioprotective effects were assessed through tensile testing and collagenase resistance testing after irradiation at 25 kGy and 50 kGy. Gamma and e-beam irradiation produced similar degenerative effects. Crosslinkers had the highest strength at 50 kGy, EDC treated tendons had 54% and 49% higher strength than untreated, for gamma and e-beam irradiation respectively. Free radical scavengers showed protective effects up to 25 kGy, especially for ascorbate and riboflavin. Crosslinked samples had higher resistance to collagenase and over a wider dose range than scavenger-treated. Of the options studied, the data suggest EDC precrosslinking or glucose treatment provides the best maintenance of native tendon properties after exposure to ionizing irradiation.

  9. Overload and neovascularization of shoulder tendons in volleyball players

    Science.gov (United States)

    2012-01-01

    Background In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the supraspinatus tendons by oximetry. Results No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7%) than middle hitters (53.7%) (p = 0.01), opposite hitters (55.5%) (p = 0.02) and libero players (54.4%) (p = 0.008), whereas there were no differences in setters (56.2%) (p > 0.05). Conclusions The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles. PMID:22853746

  10. Overload and neovascularization of shoulder tendons in volleyball players.

    Science.gov (United States)

    Notarnicola, Angela; Fischetti, Francesco; Gallone, Donato; Moretti, Lorenzo; Pignataro, Pasquale; Tafuri, Silvio; Moretti, Biagio

    2012-08-01

    In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the supraspinatus tendons by oximetry. No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7%) than middle hitters (53.7%) (p = 0.01), opposite hitters (55.5%) (p = 0.02) and libero players (54.4%) (p = 0.008), whereas there were no differences in setters (56.2%) (p > 0.05). The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles.

  11. Overload and neovascularization of shoulder tendons in volleyball players

    Directory of Open Access Journals (Sweden)

    Notarnicola Angela

    2012-08-01

    Full Text Available Abstract Background In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the supraspinatus tendons by oximetry. Results No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7% than middle hitters (53.7% (p = 0.01, opposite hitters (55.5% (p = 0.02 and libero players (54.4% (p = 0.008, whereas there were no differences in setters (56.2% (p > 0.05. Conclusions The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles.

  12. Multipotent Mesenchymal Stem Cells from Human Subacromial Bursa: Potential for Cell Based Tendon Tissue Engineering

    Science.gov (United States)

    Song, Na; Armstrong, April D.; Li, Feng; Ouyang, Hongsheng

    2014-01-01

    Rotator cuff injuries are a common clinical problem either as a result of overuse or aging. Biological approaches to tendon repair that involve use of scaffolding materials or cell-based approaches are currently being investigated. The cell-based approaches are focused on applying multipotent mesenchymal stem cells (MSCs) mostly harvested from bone marrow. In the present study, we focused on characterizing cells harvested from tissues associated with rotator cuff tendons based on an assumption that these cells would be more appropriate for tendon repair. We isolated MSCs from bursa tissue associated with rotator cuff tendons and characterized them for multilineage differentiation in vitro and in vivo. Human bursa was obtained from patients undergoing rotator cuff surgery and cells within were isolated using collagenase and dispase digestion. The cells isolated from the tissues were characterized for osteoblastic, adipogenic, chondrogenic, and tenogenic differentiation in vitro and in vivo. The results showed that the cells isolated from bursa tissue exhibited MSCs characteristics as evidenced by the expression of putative cell surface markers attributed to MSCs. The cells exhibited high proliferative capacity and differentiated toward cells of mesenchymal lineages with high efficiency. Bursa-derived cells expressed markers of tenocytes when treated with bone morphogenetic protein-12 (BMP-12) and assumed aligned morphology in culture. Bursa cells pretreated with BMP-12 and seeded in ceramic scaffolds formed extensive bone, as well as tendon-like tissue in vivo. Bone formation was demonstrated by histological analysis and immunofluorescence for DMP-1 in tissue sections made from the scaffolds seeded with the cells. Tendon-like tissue formed in vivo consisted of parallel collagen fibres typical of tendon tissues. Bursa-derived cells also formed a fibrocartilagenous tissue in the ceramic scaffolds. Taken together, the results demonstrate a new source of MSCs with a

  13. Demineralized Bone Matrix to Augment Tendon-Bone Healing: A Systematic Review.

    Science.gov (United States)

    Hexter, Adam T; Pendegrass, Catherine; Haddad, Fares; Blunn, Gordon

    2017-10-01

    Following injury to the rotator cuff and anterior cruciate ligament, a direct enthesis is not regenerated, and healing occurs with biomechanically inferior fibrous tissue. Demineralized bone matrix (DBM) is a collagen scaffold that contains growth factors and is a promising biological material for tendon and ligament repair because it can regenerate a direct fibrocartilaginous insertion via endochondral ossification. To provide a comprehensive review of the literature investigating the use of DBM to augment tendon-bone healing in tendon repair and anterior cruciate ligament reconstruction (ACLR). Systematic review. Electronic databases (MEDLINE and EMBASE) were searched for preclinical and clinical studies that evaluated the use of DBM in tendon repair and ACLR. Search terms included the following: ("demineralized bone matrix" OR "demineralized cortical bone") AND ("tissue scaffold" OR "tissue engineering" OR "ligament" OR "tendon" OR "anterior cruciate ligament" OR "rotator cuff"). Peer-reviewed articles written in English were included, and no date restriction was applied (searches performed February 10, 2017). Methodological quality was assessed with peer-reviewed scoring criteria. The search strategy identified 339 articles. After removal of duplicates and screening according to inclusion criteria, 8 studies were included for full review (tendon repair, n = 4; ACLR, n = 4). No human clinical studies were identified. All 8 studies were preclinical animal studies with good methodological quality. Five studies compared DBM augmentation with non-DBM controls, of which 4 (80%) reported positive findings in terms of histological and biomechanical outcomes. Preclinical evidence indicates that DBM can improve tendon-bone healing, although clinical studies are lacking. A range of animal models of tendon repair and ACLR showed that DBM can re-create a direct fibrocartilaginous enthesis, although the animal models are not without limitations. Before clinical trials are

  14. Functional adaptation of tendon and skeletal muscle to resistance training in three patients with genetically verified classic Ehlers Danlos Syndrome

    DEFF Research Database (Denmark)

    Møller, Mathias Bech; Kjær, Michael; Svensson, René Brüggebusch

    2014-01-01

    N, and 117 to 123 W). The tendon stiffness was tested and an average increase in response to physical training, from 1795 to 2519 N/mm was found. On average, the training loads both in upper and lower body exercises increased by around 30% over the training period. When testing balance, the average......BACKGROUND: tendon and skeletal muscle function adapts to physical training of resistive nature, but it is unknown to what extent persons with genetically altered connective tissue - who have a higher than normal tendon extensibility - will obtain any effect upon their tendon and muscle when...... undergoing muscle strength training. We investigated patients with classical Ehlers Danlos Syndrome (EDS) (collagen type V defect) who display articular hypermobility, skin extensibility and tissue fragility. METHODS: subjects underwent strength training 3 times a week for 4 months and were tested before...

  15. On the synthesis of tailored biomimetic hydroxyapatite nanoplates through a bioinspired approach in the presence of collagen or chitosan and L-arginine.

    Science.gov (United States)

    Tsetsekou, A; Brasinika, D; Vaou, V; Chatzitheodoridis, E

    2014-10-01

    Controlling the structure of hydroxyapatite nanocrystals is vital for acquiring a consistent product. In an effort to synthesize crystals mimicking the morphology of natural bone's apatite, a bioinspired process was developed based on the use of a natural biomacromolecule, collagen or chitosan, in conjunction with l-arginine to direct the formation of hydroxyapatite from H3PO4 and Ca(OH)2. Different cases were investigated by employing various concentrations of the precursors and two molar ratios of Ca/P 1/1 and 10/6. The reaction was carried out at basic pH conditions and at biomimetic temperature (40°C). The resulting aqueous suspensions were characterized in terms of their rheological behavior, whereas the derived powders were fully evaluated by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction analysis and Raman spectroscopy. The analysis showed that in all cases, the only phase detected was hydroxyapatite of a plate-like morphology very similar to that of natural apatite. The homogeneity of the morphology and the crystal size distribution depend on the precursors' final concentration with the mean size ranging from 5 nm up to 20 nm. The powder that demonstrated the best characteristics in terms of homogeneity was that produced in the presence of collagen for molar ratio of Ca/P 1/1. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Synthesis and character investigation of new collagen Hydrolysate/polyvinyl alcohol/hydroxyapatite Polymer-Nano-Porous Membranes: I. Experimental design optimization in thermal and structural properties.

    Science.gov (United States)

    Imanieh, Hossein; Aghahosseini, Hamideh

    2013-12-01

    Development of bioorganic-inorganic composites has drawn eyes to extensive attention in biomedical fields and tissue engineering. So many attempts to prepare hydroxyapatite (HA), in conjunction with various binders including polyvinyl alcohol (PVA), and collagen has performed for late 20 years. We applied a method based on the phase separation for making of polymer porous membranes. This procedure is induced through the addition of a small quantity of water (polymer-rich phase) to a solution with HA precursors (polymer-poor phase). Thermal and structural composite properties of collagen Hydrolysate (CH)-PVA/HA Polymer-Nano-Porous Membranes were analyzed by Design of experiment that was undertaken using D-optimal approach, to select the optimal combination of nano composites precursor. The resulted composite characters were investigated by Fourier transform infrared, scanning electron microscopy (SEM) and thermal gravimetric analysis. Based on the SEM images, this new method could be clearly concluded to porous CH-PVA/HA hybrid materials. Finally the hemocompatibility of nanocomposite membranes were evaluated by the hemolysis study.

  17. An advanced glycation endproduct (AGE)-rich diet promotes accumulation of AGEs in Achilles tendon

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Svensson, Rene B; Scheijen, Jean

    2017-01-01

    the relationship between AGE content in the diet and accumulation of AGEs in weight-bearing animal Achilles tendon. Two groups of mice (C57BL/6Ntac) were fed with either high-fat diet low in AGEs high-fat diet (HFD) (n = 14) or normal diet high in AGEs (ND) (n = 11). AGE content in ND was six to 50-fold higher......Advanced Glycation Endproducts (AGEs) accumulate in long-lived tissue proteins like collagen in bone and tendon causing modification of the biomechanical properties. This has been hypothesized to raise the risk of orthopedic injury such as bone fractures and tendon ruptures. We evaluated...... both ND and HFD) (P diet (ND) resulted in an increase in CML (P

  18. The fate of tendon grafts used to reconstruct the digital annular pulleys.

    Science.gov (United States)

    Deffino, H L; Barbieri, C H; Velludo, M A

    1991-02-01

    An experimental morphological study on the reconstruction of the digital annular pulleys has been carried out in dogs. The segment corresponding to zones 1 and 2 of the flexor apparatus of the 2nd and 5th digits of the left forepaw was chosen for the experiment. The whole flexor apparatus was resected and a single digital pulley (A 2) was reconstructed, using segments of the animals own deep flexor tendon. A length of silicone rubber tube was used as tendon spacer. The new pulleys showed marked degeneration of the collagen fibres and thinning which increased with time and may be the cause of decrease in strength. A layer of mesothelial cells with secretory properties developed at the interface between the tendon graft and the spacer.

  19. Influence of nanofibers on growth and gene expression of human tendon derived fibroblast

    Directory of Open Access Journals (Sweden)

    Schmitt Jan

    2010-02-01

    Full Text Available Abstract Background Rotator cuff tears are a common and frequent lesion especially in older patients. The mechanisms of tendon repair are not fully understood. Common therapy options for tendon repair include mini-open or arthroscopic surgery. The use of growth factors in experimental studies is mentioned in the literature. Nanofiber scaffolds, which provide several criteria for the healing process, might be a suitable therapy option for operative treatment. The aim of this study was to explore the effects of nanofiber scaffolds on human tendon derived fibroblasts (TDF's, as well as the gene expression and matrix deposition of these fibroblasts. Methods Nanofibers composed of PLLA and PLLA/Col-I were seeded with human tendon derived fibroblasts and cultivated over a period of 22 days under growth-inductive conditions, and analyzed during the course of culture, with respect to gene expression of different extra cellular matrix components such as collagens, bigylcan and decorin. Furthermore, we measured cell densities and proliferation by using fluorescene microscopy. Results PLLA nanofibers possessed a growth inhibitory effect on TDF's. Furthermore, no meaningful influence on the gene expression of collagen I, collagen III and decorin could be observed, while the expression of collagen X increased during the course of cultivation. On the other hand, PLLA/Col-I blend nanofibers had no negative influence on the growth of TDF's. Furthermore, blending PLLA nanofibers with collagen had a positive effect on the gene expression of collagen I, III, X and decorin. Here, gene expression indicated that focal adherence kinases might be involved. Conclusion This study indicates that the use of nanofibers influence expression of genes associated with the extra cellular matrix formation. The composition of the nanofibers plays a critical role. While PLLA/Col-I blend nanofibers enhance the collagen I and III formation, their expression on PLLA nanofibers was

  20. Pseudomembranous collagenous colitis.

    Science.gov (United States)

    Yuan, Shan; Reyes, Victoria; Bronner, Mary P

    2003-10-01

    The classic clinical and histologic features of collagenous colitis are well characterized; however, the acute or neutrophilic inflammatory changes that may accompany this entity are less well established. In this report of 10 patients, we describe the first series of pseudomembranous collagenous colitis. Because superimposed Clostridium difficile infection was only demonstrated in one patient and no other causes of pseudomembranous colitis were evident in the remaining nine patients, we conclude that pseudomembranes are part of the spectrum of collagenous colitis itself. This case series illustrates the importance of searching for collagenous colitis in the evaluation of pseudomembranous colitis. At the same time, superimposed infectious or ischemic etiologies need to be excluded clinically in any patient with superimposed pseudomembranes. The existence of pseudomembranes in collagenous colitis also lends support to the hypothesis that toxin- and/or ischemia-mediated injury may be involved in the pathogenesis of collagenous colitis.

  1. Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: First pre-clinical study on a murine model

    Energy Technology Data Exchange (ETDEWEB)

    Dallaudière, Benjamin, E-mail: bendallau64@hotmail.fr [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Inserm U698, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Lempicki, Marta [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Pesquer, Lionel [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Louedec, Liliane [Inserm U698, Hôpital universitaire Bichat, Paris (France); Preux, Pierre Marie [Laboratoire de Biostatistiques, Faculté de médecine, Limoges (France); Meyer, Philippe [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Hess, Agathe [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Durieux, Marie Hèlène Moreau [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Hummel, Vincent; Larbi, Ahmed [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Deschamps, Lydia [Service d’ Anatomopathologie, Hôpital universitaire Bichat, Paris (France); and others

    2013-12-01

    Purpose: Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity. Materials and method: Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1{sup ®} (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T−) after injecting AA in 40 (AAT−). Results: All AAT+ showed a better joint mobilization compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p < 0.004), and less disorganized collagen fibers and neovessels on histology (p < 0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology (p > 0.05). Comparison between AAT− and T− showed no AA toxicity on tendon (p = 0.18). Conclusion: Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendon's healing, with no local toxicity.

  2. Adult Cells Combined With Platelet-Rich Plasma for Tendon Healing

    Science.gov (United States)

    Rubio-Azpeitia, Eva; Sánchez, Pello; Delgado, Diego; Andia, Isabel

    2017-01-01

    Background: The combination of cells with platelet-rich plasma (PRP) may fulfill tendon deficits and help overcome the limited ability of tendons to heal. Purpose: To examine the suitability of 3 human cell types in combination with PRP and the potential impact of the tenocyte-conditioned media (CM) to enhance tendon healing. Study Design: Controlled laboratory study. Methods: Tenocytes, bone marrow–derived mesenchymal stem cells, and skin fibroblasts were cultured in 3-dimensional PRP hydrogels supplemented or not with CM, and cell proliferation and migration were examined. The effect of tendon-derived CM on matrix-forming phenotype and secretion of inflammatory proteins was determined through their administration to mesenchymal stem cells, tendon, and skin fibroblasts by reverse transcription quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Results: Differences were found in the matrix-forming phenotype between each of the cell types. The ratio of collagen I:collagen III was greater in bone marrow–derived mesenchymal stem cells than in skin fibroblasts and tenocytes. The bone marrow–derived mesenchymal stem cells expressed increased levels of cartilage-related genes than tenocytes or skin fibroblasts. The presence of the tenocyte-CM stimulated basic healing mechanisms including proliferation and chemotaxis in all cell types. In addition, the tenocyte-CM modified the matrix-forming phenotype of every cell type when cultured in PRP hydrogels. Each cell type secreted interleukin-6, interleukin-8, and monocyte chemotactic protein-1 in PRP hydrogels, but mesenchymal stem cells secreted less interleukin-8 and monocyte chemotactic protein-1 than tenocytes or skin fibroblasts. Conclusion: The tenocyte-CM combined with PRP stimulated tenogenesis in mesenchymal stem cells and in skin fibroblasts and reduced the secretion of inflammatory proteins. Clinical Relevance: Modifying the target tissue with PRP prior to cell

  3. Experimental Diabetes Alters the Morphology and Nano-Structure of the Achilles Tendon.

    Science.gov (United States)

    Oliveira, Rodrigo Ribeiro de; Medina de Mattos, Rômulo; Magalhães Rebelo, Luciana; Guimarães Meireles Ferreira, Fernanda; Tovar-Moll, Fernanda; Eurico Nasciutti, Luiz; de Castro Brito, Gerly Anne

    2017-01-01

    Although of several studies that associate chronic hyperglycemia with tendinopathy, the connection between morphometric changes as witnessed by magnetic resonance (MR) images, nanostructural changes, and inflammatory markers have not yet been fully established. Therefore, the present study has as a hypothesis that the Achilles tendons of rats with diabetes mellitus (DM) exhibit structural changes. The animals were randomly divided into two experimental groups: Control Group (n = 06) injected with a vehicle (sodium citrate buffer solution) and Diabetic Group (n = 06) consisting of rats submitted to intraperitoneal administration of streptozotocin. MR was performed 24 days after the induction of diabetes and images were used for morphometry using ImageJ software. Morphology of the collagen fibers within tendons was examined using Atomic Force microscopy (AFM). An increase in the dimension of the coronal plane area was observed in the diabetic group (8.583 ± 0.646 mm2/100g) when compared to the control group (4.823 ± 0.267 mm2/100g) resulting in a significant difference (p = 0.003) upon evaluating the Achilles tendons. Similarly, our analysis found an increase in the size of the transverse section area in the diabetic group (1.328 ± 0.103 mm2/100g) in comparison to the control group (0.940 ± 0.01 mm2/100g) p = 0.021. The tendons of the diabetic group showed great irregularity in fiber bundles, including modified grain direction and jagged junctions and deformities in the form of collagen fibrils bulges. Despite the morphological changes observed in the Achilles tendon of diabetic animals, IL1 and TNF-α did not change. Our results suggest that DM promotes changes to the Achilles tendon with important structural modifications as seen by MR and AFM, excluding major inflammatory changes.

  4. Autologous tendon-derived cell-seeded nanofibrous scaffolds improve rotator cuff repair in an age-dependent fashion.

    Science.gov (United States)

    Huegel, Julianne; Kim, Dong Hwa; Cirone, James M; Pardes, Adam M; Morris, Tyler R; Nuss, Courtney A; Mauck, Robert L; Soslowsky, Louis J; Kuntz, Andrew F

    2017-06-01

    Rotator cuff tendon tears are one of the most common shoulder pathologies, especially in the aging population. Due to a poor healing response and degenerative changes associated with aging, rotator cuff repair failure remains common. Although cell-based therapies to augment rotator cuff repair appear promising, it is unknown whether the success of such a therapy is age-dependent. We hypothesized that autologous cell therapy would improve tendon-to-bone healing across age groups, with autologous juvenile cells realizing the greatest benefit. In this study, juvenile, adult, and aged rats underwent bilateral supraspinatus tendon repair with augmentation of one shoulder with autologous tendon-derived cell-seeded polycaprolactone scaffolds. At 8 weeks, shoulders treated with cells in both juvenile and aged animals exhibited increased cellularity, increased collagen organization, and improved mechanical properties. No changes between treated and control limbs were seen in adult rats. These findings suggest that cell delivery during supraspinatus repair initiates earlier matrix remodeling in juvenile and aged animals. This may be due to the relative "equilibrium" of adult tendon tissue with regards to catabolic and anabolic processes, contrasted with actively growing juvenile tendons and degenerative aged tendons. This study demonstrates the potential for autologous cell-seeded scaffolds to improve repairs in both the juvenile and aged population. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1250-1257, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  5. Human multipotent mesenchymal stem cells improve healing after collagenase tendon injury in the rat.

    Science.gov (United States)

    Machova Urdzikova, Lucia; Sedlacek, Radek; Suchy, Tomas; Amemori, Takashi; Ruzicka, Jiri; Lesny, Petr; Havlas, Vojtech; Sykova, Eva; Jendelova, Pavla

    2014-04-09

    Mesenchymal stromal cells attract much interest in tissue regeneration because of their capacity to differentiate into mesodermal origin cells, their paracrine properties and their possible use in autologous transplantations. The aim of this study was to investigate the safety and reparative potential of implanted human mesenchymal stromal cells (hMSCs), prepared under Good Manufacturing Practice (GMP) conditions utilizing human mixed platelet lysate as a culture supplement, in a collagenase Achilles tendon injury model in rats. Eighty-one rats with collagenase-induced injury were divided into two groups. The first group received human mesenchymal stromal cells injected into the site of injury 3 days after lesion induction, while the second group received saline. Biomechanical testing, morphometry and semiquantitative immunohistochemistry of collagens I, II and III, versican and aggrecan, neovascularization, and hMSC survival were performed 2, 4, and 6 weeks after injury. Human mesenchymal stromal cell-treated rats had a significantly better extracellular matrix structure and a larger amount of collagen I and collagen III. Neovascularization was also increased in hMSC-treated rats 2 and 4 weeks after tendon injury. MTCO2 (Cytochrome c oxidase subunit II) positivity confirmed the presence of hMSCs 2, 4 and 6 weeks after transplantation. Collagen II deposits and alizarin red staining for bone were found in 6 hMSC- and 2 saline-treated tendons 6 weeks after injury. The intensity of anti-versican and anti-aggrecan staining did not differ between the groups. hMSCs can support tendon healing through better vascularization as well as through larger deposits and better organization of the extracellular matrix. The treatment procedure was found to be safe; however, cartilage and bone formation at the implantation site should be taken into account when planning subsequent in vivo and clinical trials on tendinopathy as an expected adverse event.

  6. Collagens and proteoglycans of the corneal extracellular matrix

    Directory of Open Access Journals (Sweden)

    Y.M. Michelacci

    2003-08-01

    Full Text Available The cornea is a curved and transparent structure that provides the initial focusing of a light image into the eye. It consists of a central stroma that constitutes 90% of the corneal depth, covered anteriorly with epithelium and posteriorly with endothelium. Its transparency is the result of the regular spacing of collagen fibers with remarkably uniform diameter and interfibrillar space. Corneal collagen is composed of heterotypic fibrils consisting of type I and type V collagen molecules. The cornea also contains unusually high amounts of type VI collagen, which form microfibrillar structures, FACIT collagens (XII and XIV, and other nonfibrillar collagens (XIII and XVIII. FACIT collagens and other molecules, such as leucine-rich repeat proteoglycans, play important roles in modifying the structure and function of collagen fibrils.Proteoglycans are macromolecules composed of a protein core with covalently linked glycosaminoglycan side chains. Four leucine-rich repeat proteoglycans are present in the extracellular matrix of corneal stroma: decorin, lumican, mimecan and keratocan. The first is a dermatan sulfate proteoglycan, and the other three are keratan sulfate proteoglycans. Experimental evidence indicates that the keratan sulfate proteoglycans are involved in the regulation of collagen fibril diameter, and dermatan sulfate proteoglycan participates in the control of interfibrillar spacing and in the lamellar adhesion properties of corneal collagens. Heparan sulfate proteoglycans are minor components of the cornea, and are synthesized mainly by epithelial cells. The effect of injuries on proteoglycan synthesis is discussed.

  7. The effect of running, strength, and vibration strength training on the mechanical, morphological, and biochemical properties of the Achilles tendon in rats

    DEFF Research Database (Denmark)

    Legerlotz, Kirsten; Schjerling, Peter; Langberg, Henning

    2007-01-01

    on the mechanical, morphological, and biochemical properties of the Achilles tendon. Sixty-four female Sprague-Dawley rats were divided into five groups: nonactive age-matched control (AMC; n = 20), voluntary wheel running (RT; n = 20), vibration strength-trained (LVST; n = 12), high-vibration strength......-trained (HVST; n = 6), and high strength-trained (HST; n = 6) group. After a 12-wk-long experimental period, the Achilles tendon was tested mechanically and the cross-sectional area, the soleus and gastrocnemius muscle mass, and mRNA concentration of collagen I, collagen III, tissue inhibitor...

  8. Acute calcific tendinitis simulating tendon sheath infection.

    Science.gov (United States)

    Omololu, B; Alonge, T O; Ogunlade, S O

    2001-01-01

    Tendon sheath infection has catastrophic consequences if not diagnosed. We present acute calcific tendinitis, a simulator of tendon sheath infection with a good prognosis in a 14 year old athletic tennis player.

  9. Nanoscale characterization of isolated individual type I collagen fibrils: polarization and piezoelectricity

    Energy Technology Data Exchange (ETDEWEB)

    Minary-Jolandan, Majid; Yu Minfeng [Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, 1206 West Green Street, Urbana, IL 61801 (United States)], E-mail: mfyu@uiuc.edu

    2009-02-25

    Piezoresponse force microscopy was applied to directly study individual type I collagen fibrils with diameters of {approx}100 nm isolated from bovine Achilles tendon. It was revealed that single collagen fibrils behave predominantly as shear piezoelectric materials with a piezoelectric coefficient on the order of 1 pm V{sup -1}, and have unipolar axial polarization throughout their entire length. It was estimated that, under reasonable shear load conditions, the fibrils were capable of generating an electric potential up to tens of millivolts. The result substantiates the nanoscale origin of piezoelectricity in bone and tendons, and implies also the potential importance of the shear load-transfer mechanism, which has been the principle basis of the nanoscale mechanics model of collagen, in mechanoelectric transduction in bone.

  10. Collagen and gelatin.

    Science.gov (United States)

    Liu, Dasong; Nikoo, Mehdi; Boran, Gökhan; Zhou, Peng; Regenstein, Joe M

    2015-01-01

    Collagen and gelatin have been widely used in the food, pharmaceutical, and cosmetic industries due to their excellent biocompatibility, easy biodegradability, and weak antigenicity. Fish collagen and gelatin are of renewed interest, owing to the safety and religious concerns of their mammalian counterparts. The structure of collagen has been studied using various modern technologies, and interpretation of the raw data should be done with caution. The structure of collagen may vary with sources and seasons, which may affect its applications and optimal extraction conditions. Numerous studies have investigated the bioactivities and biological effects of collagen, gelatin, and their hydrolysis peptides, using both in vitro and in vivo assay models. In addition to their established nutritional value as a protein source, collagen and collagen-derived products may exert various potential biological activities on cells in the extracellular matrix through the corresponding food-derived peptides after ingestion, and this might justify their applications in dietary supplements and pharmaceutical preparations. Moreover, an increasing number of novel applications have been found for collagen and gelatin. Therefore, this review covers the current understanding of the structure, bioactivities, and biological effects of collagen, gelatin, and gelatin hydrolysates as well as their most recent applications.

  11. Basic mechanisms of tendon fatigue damage

    OpenAIRE

    Neviaser, Andrew; Andarawis-Puri, Nelly; Flatow, Evan

    2012-01-01

    Pathologic processes intrinsic and extrinsic to the tendons have been proposed as the underlying cause of rotator cuff disease, but the precise etiology is not known. Tear formation is, in part, attributable to the accumulation of subrupture tendon fatigue damage. We review the molecular, mechanical, and structural changes induced in tendons subjected to controlled amounts of fatigue loading in an animal model of early tendinopathy. The distinct tendon responses to low and moderate levels of ...

  12. Collagen type I as a ligand for receptor-mediated signaling

    Science.gov (United States)

    Boraschi-Diaz, Iris; Wang, Jennifer; Mort, John S.; Komarova, Svetlana V.

    2017-05-01

    Collagens form the fibrous component of the extracellular matrix in all multi-cellular animals. Collagen type I is the most abundant collagen present in skin, tendons, vasculature, as well as the organic portion of the calcified tissue of bone and teeth. This review focuses on numerous receptors for which collagen acts as a ligand, including integrins, discoidin domain receptors DDR1 and 2, OSCAR, GPVI, G6b-B and Lair-1 of the leukocyte receptor complex and mannose family receptor uPARAP/Endo 180. We explore the process of collagen production and self-assembly, as well as its degradation by collagenases and gelatinases in order to predict potential temporal and spatial sites of action of different collagen receptors. While the interactions of the mature collagen matrix with integrins and DDR are well-appreciated, potential signals from immature matrix as well as collagen degradation products are possible but not yet described. The role of multiple collagen receptors in physiological processes and their contribution to pathophysiology of diseases affecting collagen homeostasis require further studies.

  13. Collagen Type I as a Ligand for Receptor-Mediated Signaling

    Directory of Open Access Journals (Sweden)

    Iris Boraschi-Diaz

    2017-05-01

    Full Text Available Collagens form the fibrous component of the extracellular matrix in all multi-cellular animals. Collagen type I is the most abundant collagen present in skin, tendons, vasculature, as well as the organic portion of the calcified tissue of bone and teeth. This review focuses on numerous receptors for which collagen acts as a ligand, including integrins, discoidin domain receptors DDR1 and 2, OSCAR, GPVI, G6b-B, and LAIR-1 of the leukocyte receptor complex (LRC and mannose family receptor uPARAP/Endo180. We explore the process of collagen production and self-assembly, as well as its degradation by collagenases and gelatinases in order to predict potential temporal and spatial sites of action of different collagen receptors. While the interactions of the mature collagen matrix with integrins and DDR are well-appreciated, potential signals from immature matrix as well as collagen degradation products are possible but not yet described. The role of multiple collagen receptors in physiological processes and their contribution to pathophysiology of diseases affecting collagen homeostasis require further studies.

  14. Forkhead box protein P1 as a downstream target of transforming growth factor-β induces collagen synthesis and correlates with a more stable plaque phenotype.

    Science.gov (United States)

    Bot, Pieter T; Grundmann, Sebastian; Goumans, Marie-José; de Kleijn, Dominique; Moll, Frans; de Boer, Onno; van der Wal, Allard C; van Soest, Alex; de Vries, Jean-Paul; van Royen, Niels; Piek, Jan J; Pasterkamp, Gerard; Hoefer, Imo E

    2011-09-01

    Atherosclerosis is an inflammatory disease, modulated by plaque stabilizing and de-stabilizing cell populations such as infiltrating monocytes and vascular smooth muscle cells (vSMCs). Transcription factors regulating proliferation and differentiation of atherosclerosis relevant cell types are of interest in this context. The forkhead box transcription factor FoxP1 modulates monocyte differentiation. We studied FoxP1 expression in atherosclerotic tissue, correlated FoxP1 expression with plaque characteristics and identified associations between FoxP1 and plaque proteins. 116 Atherosclerotic plaques from carotid endarterectomy samples were histologically classified (fibrous, fibroatheromatous, atheromatous) and subjected to semi-quantitative protein analysis. Macrophage, SMC content and intraplaque thrombus amount were determined histologically. FoxP1 expression was investigated by western blotting and immunohistochemistry. In addition FoxP1 was overexpressed in vitro to identify causal relations between FoxP1 and plaque proteins. FoxP1 expression was observed in SMCs, macrophages, endothelial cells and T-cells within the plaque. High SMC and collagen content correlated with increased FoxP1 isoform (72 kD and 95 kD) levels. 72 kD FoxP1 expression was lower in plaques containing intraplaque thrombus. FoxP1 correlated with active intraplaque TGFβ signaling. In vitro stimulation of SMCs with TGFβ resulted in increased FoxP1 levels. 72 kD FoxP1 correlated with expression of pro-fibrotic EGR-1 and increased Col1A1 expression. FoxP1 is expressed by different cell types in atherosclerotic lesions and associated with more stable plaque characteristics and intraplaque TGFβ signaling. FoxP1 expression in vitro is induced by TGFβ, resulting in increased collagen and EGR-1 expression, providing a mechanism for the observed association with a more stable plaque phenotype. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. MRI of normal achilles tendon

    Energy Technology Data Exchange (ETDEWEB)

    Rollandi, G.A. [Institute of Radiology, Univ. of Genoa (Italy); Bertolotto, M. [Institute of Radiology, Univ. of Genoa (Italy); Perrone, R. [Institute of Radiology, Univ. of Genoa (Italy); Garlaschi, G. [Institute of Radiology, Univ. of Genoa (Italy); Derchi, L.E. [Institute of Radiology, Univ. of Genoa (Italy)

    1995-12-01

    To investigate the normal internal structure of tendons 11 volunteers without clinical evidence of tendinopathy were examined using conventional spin-echo T1-, T2- and proton-density weighted sequences. The Achilles tendon was chosen because of its high frequency of injury in athletic activity, large size, superficial position and because it is oriented nearly parallel to the static magnetic field, therefore minimizing the ``magic angle phenomenon``. The tendons exhibited areas of slighly increased signal in four T1-weighted and in all but one proton-density-weighted scans. No intratendinous signal was detected in T2-weighted images. The possible origin of these findings is discussed. We conclude that the knowledge of these normal signals may be useful to avoid incorrectly diagnosing as pathological. (orig.). With 2 figs.

  16. Achilles tendon reflex measuring system

    Science.gov (United States)

    Szebeszczyk, Janina; Straszecka, Joanna

    1995-06-01

    The examination of Achilles tendon reflex is widely used as a simple, noninvasive clinical test in diagnosis and pharmacological therapy monitoring in such diseases as: hypothyroidism, hyperthyroidism, diabetic neuropathy, the lower limbs obstructive angiopathies and intermittent claudication. Presented Achilles tendon reflect measuring system is based on the piezoresistive sensor connected with the cylinder-piston system. To determinate the moment of Achilles tendon stimulation a detecting circuit was used. The outputs of the measuring system are connected to the PC-based data acquisition board. Experimental results showed that the measurement accuracy and repeatability is good enough for diagnostics and therapy monitoring purposes. A user friendly, easy-to-operate measurement system fulfills all the requirements related to recording, presentation and storing of the patients' reflexograms.

  17. Histological and Immunohistochemical Evaluation of Autologous Cultured Bone Marrow Mesenchymal Stem Cells and Bone Marrow Mononucleated Cells in Collagenase-Induced Tendinitis of Equine Superficial Digital Flexor Tendon

    Science.gov (United States)

    Crovace, Antonio; Lacitignola, Luca; Rossi, Giacomo; Francioso, Edda

    2010-01-01

    The aim of this study was to compare treatment with cultured bone marrow stromal cells (cBMSCs), bone marrow Mononucleated Cells (BMMNCs), and placebo to repair collagenase-induced tendinitis in horses. In six adult Standardbred horses, 4000 IU of collagenase were injected in the superficial digital flexor tendon (SDFT). Three weeks after collagenase treatment, an average of either 5.5 × 106 cBMSCs or 1.2 × 108 BMMNCs, fibrin glue, and saline solution was injected intralesionally in random order. In cBMSC- and BMMNCS-treated tendons, a high expression of cartilage oligomeric matrix protein (COMP) and type I collagen, but low levels of type III collagen were revealed by immunohistochemistry, with a normal longitudinally oriented fiber pattern. Placebo-treated tendons expressed very low quantities of COMP and type I collagen but large numbers of randomly oriented type III collagen fibers. Both cBMSC and BMMNCS grafts resulted in a qualitatively similar heling improvement of tendon extracellular matrix, in terms of the type I/III collagen ratio, fiber orientation, and COMP expression. PMID:20445779

  18. Midportion Achilles tendinosis and the plantaris tendon.

    Science.gov (United States)

    Alfredson, Håkan

    2011-10-01

    When re-operating patients with midportion Achilles tendinosis, having had a poor effect of ultrasound (US) and Doppler-guided scraping, the author found the involvement of the plantaris tendon to be a likely reason for the poor result. The aim of this study was to investigate the occurrence of a plantaris tendon in close relation to the Achilles tendon in consecutive patients with midportion Achilles tendinosis undergoing treatment with US and Doppler-guided scraping. This study includes 73 consecutive tendons with chronic painful midportion Achilles tendinosis, where US+Doppler examination showed thickening, irregular tendon structure, hypo-echoic regions, and localised high blood flow outside and inside the ventral Achilles midportion. The tendons were treated with US+Doppler-guided scraping, via a medial incision. If there was a plantaris tendon located in close relation to the medial Achilles, it was extirpated. An invaginated, or 'close by located', enlarged plantaris tendon was found in 58 of 73 (80%) tendons. Preliminary clinical results of the combined procedure, US + Doppler-guided surgical scraping and extirpation of the plantaris tendon, are very promising. A thickened plantaris tendon located in close relation to the medial Achilles seems common in patients with chronic painful midportion tendinosis. The role of the plantaris tendon in midportion Achilles tendinosis needs to be further evaluated and should be kept in mind when treating this condition.

  19. Heel pain and Achilles tendonitis -- aftercare

    Science.gov (United States)

    ... About Your Injury The Achilles tendon connects your calf muscles to your heel bone. Together, they help ... running or jumping. Do activities that do not strain the tendon, such as ... and strengthen the muscles and tendon. Range of motion exercises will help ...

  20. Spontaneous Achilles tendon rupture in alkaptonuria | Mohammed ...

    African Journals Online (AJOL)

    Spontaneous Achilles tendon ruptures are uncommon. We present a 46-year-old man with spontaneous Achilles tendon rupture due to ochronosis. To our knowledge, this has not been previously reported in Sudan literature. The tendon of the reported patient healed well after debridement and primary repairs.

  1. Chronic Achilles tendon rupture reconstructed using hamstring tendon autograft.

    Science.gov (United States)

    Ellison, Philip; Mason, Lyndon William; Molloy, Andrew

    2016-03-01

    Chronic rupture of the Achilles tendon (delayed diagnosis of more than 4 weeks) can result in retraction of the tendon and inadequate healing. Direct repair may not be possible and augmentation methods are challenging when the defect exceeds 5-6 cm, especially if the distal stump is grossly tendinopathic. We describe our method of Achilles tendon reconstruction with ipsilateral semitendinosis autograft and interference screw fixation in a patient with chronic rupture, a 9 cm defect and gross distal tendinopathy. Patient reported outcome measures consistently demonstrated improved health status at 12 months post surgery: MOXFQ-Index 38-25, EQ5D-5L 18-9, EQ VAS 70-90 and VISA-A 1-64. The patient was back to full daily function, could single leg heel raise and was gradually returning to sport. No complications or adverse events were recorded. Reconstruction of chronic tears of the Achilles tendon with large defects and gross tendinopathy using an ipsilateral semitendinosis autograft and interference screw fixation can achieve satisfactory improvements in patient reported outcomes up to 1 year post-surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Recombinant fibroblast growth protein enhances healing ability of experimentally induced tendon injury in vivo.

    Science.gov (United States)

    Oryan, A; Moshiri, A

    2014-06-01

    This study was designed to investigate the effects of recombinant human basic fibroblast growth factor (bFGF) on a complete superficial digital flexor tendon (SDFT) rupture after surgical repair in rabbits. Eighty mature New Zealand White rabbits of both sexes were randomly divided into two equal groups: Treated and Control. Each group was subdivided into two 28- and 84-day post-injury subgroups. After tenotomy and surgical repair, the animals were immobilized for 14 days. In the treated group, bFGF was directly applied subcutaneously over the lesion on days 3, 7 and 10 after injury. The control animals received normal saline injection of the same viscosity and volume and at the same intervals. Ultrasonographical observations were conducted at weekly intervals. The animals were euthanized at 28 and 84 days after injury. The tendons were evaluated at macroscopic, histopathologic and ultrastructural levels and were assessed for biomechanical and percentage dry weight parameters. Compared to injured control animals, treated animals showed a decrease in the diameter of the injured tendon and peritendinous adhesion as well as increased tenoblast proliferation, collagen production and ultimate strength of the injured tendons (p tendons compared to controls (p = 0.001). bFGF showed promising curative effects on restoration of the biomechanical and morphological properties of the ruptured SDFT in rabbits and may be applicable in clinical studies. Copyright © 2012 John Wiley & Sons, Ltd.

  3. Nutrition of flexor tendons in monkeys.

    Science.gov (United States)

    Manske, P R; Bridwell, K; Whiteside, L A; Lesker, P A

    1978-10-01

    The hydrogen washout technique was used to investigate the role of synovial diffusion versus vascular perfusion in the nutrition of monkey flexor tendons within the digital sheath. There was no significant difference in the uptake and washout of hydrogen tracer by tendons in contact with synovium but detached from the surrounding vasculature, compared to control tendons. However, there was insignificant uptake of tracer by tendons with intact vasculature, but separated from synovium. Synovial diffusion is a primary nutrient pathway of monkey flexor tendons within the digital sheath.

  4. Can PRP effectively treat injured tendons?

    Science.gov (United States)

    Wang, James H-C

    2014-01-01

    PRP is widely used to treat tendon and other tissue injuries in orthopaedics and sports medicine; however, the efficacy of PRP treatment on injured tendons is highly controversial. In this commentary, I reason that there are many PRP- and patient-related factors that influence the outcomes of PRP treatment on injured tendons. Therefore, more basic science studies are needed to understand the mechanism of PRP on injured tendons. Finally, I suggest that better understanding of the PRP action mechanism will lead to better use of PRP for the effective treatment of tendon injuries in clinics.

  5. Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: Promoted tendon-to-bone healing and opposed corticosteroid aggravation.

    Science.gov (United States)

    Krivic, Andrija; Anic, Tomislav; Seiwerth, Sven; Huljev, Dubravko; Sikiric, Predrag

    2006-05-01

    Stable gastric pentadecapeptide BPC 157 (BPC 157, as an antiulcer agent in clinical trials for inflammatory bowel disease; PLD-116, PL 14736, Pliva, no toxicity reported) alone (without carrier) ameliorates healing of tendon and bone, respectively, as well as other tissues. Thereby, we focus on Achilles tendon-to-bone healing: tendon to bone could not be healed spontaneously, but it was recovered by this peptide. After the rat's Achilles tendon was sharply transected from calcaneal bone, agents [BPC 157 (10 microg, 10 ng, 10 pg), 6alpha-methylprednisolone (1 mg), 0.9% NaCl (5 mL)] were given alone or in combination [/kg body weight (b.w.) intraperitoneally, once time daily, first 30-min after surgery, last 24 h before analysis]. Tested at days 1, 4, 7, 10, 14, and 21 after Achilles detachment, BPC 157 improves healing functionally [Achilles functional index (AFI) values substantially increased], biomechanically (load to failure, stiffness, and Young elasticity modulus significantly increased), macro/microscopically, immunohistochemistry (better organization of collagen fibers, and advanced vascular appearance, more collagen type I). 6alpha-Methylprednisolone consistently aggravates the healing, while BPC 157 substantially reduces 6alpha-methylprednisolone healing aggravation. Thus, direct tendon-to-bone healing using stabile nontoxic peptide BPC 157 without a carrier might successfully exchange the present reconstructive surgical methods. Copyright 2006 Orthopaedic Research Society.

  6. IMPINGEMENT-SYNDROME OF PERONEUS BREVIS TENDON AFTER CALCANEAL FRACTURES (MORPHOLOGICAL ASPECTS

    Directory of Open Access Journals (Sweden)

    N. S. Konovalchuk

    2017-01-01

    Full Text Available Background. One of the main causes of pain in patients with consequences of calcaneal fractures is the lateral impingement syndrome. This term means lateral displacement of outer calcaneal wall at the moment of fracture, narrowing of anatomical space under the lateral malleolus and compression of soft tissues in this region, including tendons of short and long peroneal muscles. This leads to chronic traumatization of tendons, alteration of their normal tracking and development of tendinitis and tenosynovitis. At this moment there are no articles in foreign or Russian literature describing how prolonged traumatization influences the internal structure of the tendons. The purpose of this study was to evaluate the morphological changes in structure of peroneus brevis tendon after different duration of compression between outer wall of calcaneus and the tip of the lateral malleolus in patients with calcaneal malunion.Materials and methods. Fifteen patients with calcaneal malunion and lateral impingement syndrome were treated operatively between 2016 and 2017. To confirm the lateral impingement syndrome, the authors performed clinical examination and AP x-rays of ankle joint. Two peroneus brevis tendon specimens were obtained intraoperatively in each of 15 patients: one specimen from compressed and one from non-compressed area. Obtained specimens were histologically examined according to standard protocol.Results. Microscopically all specimens showed separation of collagen bundles with loose connective tissue degeneration, increase of vascularization and inflammation. The degree of these changes differed according to the compression duration. This allowed us to analyze the dynamics of these changes.Conclusion. The morphological changes in structure of peroneus brevis tendon during the compression between outer wall of calcaneus and the tip of the lateral malleolus correspond with dynamics of common pathologic reactions. Early stages showed signs of

  7. Composite growth factor supplementation strategies to enhance tenocyte bioactivity in aligned collagen-GAG scaffolds.

    Science.gov (United States)

    Caliari, Steven R; Harley, Brendan A C

    2013-05-01

    Biomolecular environments encountered in vivo are complex and dynamic, with combinations of biomolecules presented in both freely diffusible (liquid-phase) and sequestered (bound to the extracellular matrix) states. Strategies for integrating multiple biomolecular signals into a biomimetic scaffold provide a platform to simultaneously control multiple cell activities, such as motility, proliferation, phenotype, and regenerative potential. Here we describe an investigation elucidating the influence of the dose and mode of presentation (soluble, sequestered) of five biomolecules (stromal cell-derived factor 1α [SDF-1α], platelet-derived growth factor BB [PDGF-BB], insulin-like growth factor 1 [IGF-1], basic fibroblast growth factor [bFGF], and growth/differentiation factor 5 [GDF-5]) on the recruitment, proliferation, collagen synthesis, and genomic stability of equine tenocytes within an anisotropic collagen-GAG scaffold for tendon regeneration applications. Critically, we found that single factors led to a dose-dependent trade-off between driving tenocyte proliferation (PDGF-BB, IGF-1) versus maintenance of a tenocyte phenotype (GDF-5, bFGF). We identified supplementation schemes using factor pairs (IGF-1, GDF-5) to rescue the tenocyte phenotype and gene expression profiles while simultaneously driving proliferation. These results suggest coincident application of multi-biomolecule cocktails has a significant value in regenerative medicine applications where control of cell proliferation and phenotype are required. Finally, we demonstrated an immobilization strategy that allows efficient sequestration of bioactive levels of these factors within the scaffold network. We showed sequestration can lead to a greater sustained bioactivity than soluble supplementation, making this approach particularly amenable to in vivo translation where diffusive loss is a concern and continuous biomolecule supplementation is not feasible.

  8. Effects of 9-deoxo-16,16-dimethyl-9-methylene PGE2 on muscle contractile activity and collagen synthesis in the human cervix.

    Science.gov (United States)

    Norström, A; Bryman, I; Lindblom, B; Christensen, N J

    1985-03-01

    The in vitro effects of a stable PGE-analogue (9-deoxo-16,16-dimethyl-9-methylene PGE2 (9-methylene PGE2) on human cervical tissue was investigated. The influence of the analogue on collagen biosynthesis was studied by measuring the incorporation of 3H-proline, while smooth muscle effects were evaluated by isometric recording of contractile activity. The specimens were obtained by needle biopsy from women in early and late pregnancy and from nonpregnant women of fertile age. 9-methylene PGE2 compared with controls increased the incorporation of 3H-proline in the secretory phase and before the 9th week of pregnancy, whereas radiolabelling was decreased in the follicular phase, in the 9th-12th week and at term. With respect to incorporation of 3H-proline,9-methylene PGE2 was equipotent to PGE2. 9-methylene PGE2 inhibited spontaneous contractile activity in early as well as in late pregnancy but increased muscular activity in nonpregnant patients. The inhibitory effects of the analogue was similar to that of PGE2 but the natural compound was considerably more potent in this respect.

  9. Bioreactor Design for Tendon/Ligament Engineering

    Science.gov (United States)

    Wang, Tao; Gardiner, Bruce S.; Lin, Zhen; Rubenson, Jonas; Kirk, Thomas B.; Wang, Allan; Xu, Jiake

    2013-01-01

    Tendon and ligament injury is a worldwide health problem, but the treatment options remain limited. Tendon and ligament engineering might provide an alternative tissue source for the surgical replacement of injured tendon. A bioreactor provides a controllable environment enabling the systematic study of specific biological, biochemical, and biomechanical requirements to design and manufacture engineered tendon/ligament tissue. Furthermore, the tendon/ligament bioreactor system can provide a suitable culture environment, which mimics the dynamics of the in vivo environment for tendon/ligament maturation. For clinical settings, bioreactors also have the advantages of less-contamination risk, high reproducibility of cell propagation by minimizing manual operation, and a consistent end product. In this review, we identify the key components, design preferences, and criteria that are required for the development of an ideal bioreactor for engineering tendons and ligaments. PMID:23072472

  10. Multiple extensor tendons reconstruction with hamstring tendon grafts and flap coverage for severe dorsal hand injuries.

    Science.gov (United States)

    Ozbaydar, M; Orman, O; Ozel, O; Altan, E

    2017-10-10

    Treatment of patients with traumatic loss of skin and multiple extensor tendons on the dorsum of the hand is a challenge. The aim of this study was to assess the outcome after reconstruction of soft tissues and multiple extensor tendons in patients who suffered traumatic loss of skin and multiple extensor tendons. Ten patients were enrolled in the study. These patients underwent single-stage reconstruction with autogenous hamstring tendon grafts for multiple extensor tendon defects and fasciocutaneous flaps for coverage of dorsal hand defects. In total, 25 tendons (2 tendons in 5 patients and 3 tendons in 5 patients) were reconstructed. The semitendinosus tendon was used in all patients and the gracilis tendon was added in five patients for tendon reconstruction. Total tendon length requiring reconstruction was between 9cm and 31cm. Free anterolateral thigh flaps were used in six patients and reverse pedicled forearm flaps were used in four patients. According to Miller's scoring system, 8 fingers had excellent results, 12 fingers had good results and 5 fingers had fair results at the final follow-up. Hamstring tendons can be used satisfactorily for primary reconstruction of multiple digital extensor tendons due to their availability and compatibility, with a fasciocutaneous flap. IV. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

  11. Living nanofiber yarn-based woven biotextiles for tendon tissue engineering using cell tri-culture and mechanical stimulation.

    Science.gov (United States)

    Wu, Shaohua; Wang, Ying; Streubel, Philipp N; Duan, Bin

    2017-10-15

    Non-woven nanofibrous scaffolds have been developed for tendon graft application by using electrospinning strategies. However, electrospun nanofibrous scaffolds face some obstacles and limitations, including suboptimal scaffold structure, weak tensile and suture-retention strengths, and compact structure for cell infiltration. In this work, a novel nanofibrous, woven biotextile, fabricated based on electrospun nanofiber yarns, was implemented as a tissue engineered tendon scaffold. Based on our modified electrospinning setup, polycaprolactone (PCL) nanofiber yarns were fabricated with reproducible quality, and were further processed into plain-weaving fabrics interlaced with polylactic acid (PLA) multifilaments. Nonwoven nanofibrous PCL meshes with random or aligned fiber structures were generated using typical electrospinning as comparative counterparts. The woven fabrics contained 3D aligned microstructures with significantly larger pore size and obviously enhanced tensile mechanical properties than their nonwoven counterparts. The biological results revealed that cell proliferation and infiltration, along with the expression of tendon-specific genes by human adipose derived mesenchymal stem cells (HADMSC) and human tenocytes (HT), were significantly enhanced on the woven fabrics compared with those on randomly-oriented or aligned nanofiber meshes. Co-cultures of HADMSC with HT or human umbilical vein endothelial cells (HUVEC) on woven fabrics significantly upregulated the functional expression of most tenogenic markers. HADMSC/HT/HUVEC tri-culture on woven fabrics showed the highest upregulation of most tendon-associated markers than all the other mono- and co-culture groups. Furthermore, we conditioned the tri-cultured constructs with dynamic conditioning and demonstrated that dynamic stretch promoted total collagen secretion and tenogenic differentiation. Our nanofiber yarn-based biotextiles have significant potential to be used as engineered scaffolds to

  12. Effects of replacing soybean meal with chickpea seeds in the diet on mechanical and thermal properties of tendon tissue in broiler chicken.

    Science.gov (United States)

    Muszynski, S; Kwiecien, M; Swietlicki, M; Dobrowolski, P; Tatarczak, J; Gladyszewska, B

    2018-02-01

    The efficiency of the musculoskeletal system of broiler chickens, in particular during locomotion and in ensu