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- Bernhardsson, Magnus, 1989-, et al.
(author)
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Depletion of cytotoxic (CD8+) T cells impairs implant fixation in rat cancellous bone
- 2019
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In: Journal of Orthopaedic Research. - : John Wiley & Sons. - 0736-0266 .- 1554-527X. ; 37:4, s. 805-811
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Journal article (peer-reviewed)abstract
- As cytotoxic (CD8(+)) T cells seem to impair shaft fracture healing, we hypothesized that depletion of CD8(+) cells would instead improve healing of cancellous bone. Additionally, we also tested if CD8-depletion would influence the healing of ruptured Achilles tendons. Rats received a single injection of either anti-CD8 antibodies or saline and put through surgery 24 h later. Three different surgical interventions were performed as follows: (1) a drill hole in the proximal tibia with microCT (BV/TV) to assess bone formation; (2) a screw in the proximal tibia with mechanical evaluation (pull-out force) to assess fracture healing; (3) Achilles tendon transection with mechanical evaluation (force-at-failure) to assess tendon healing. Furthermore, CD8-depletion was confirmed with flow cytometry on peripheral blood. Flow cytometric analysis confirmed depletion of CD8(+) cells (p amp;lt; 0.001). Contrary to our hypothesis, depletion of CD8(+) cells reduced the implant pull-out force by 19% (p amp;lt; 0.05) and stiffness by 34% (p amp;lt; 0.01), although the bone formation in the drill holes was the same as in the controls. Tendon healing was unaffected by CD8-depletion. Our results suggest that CD8(+) cells have an important part in cancellous bone healing.
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- Dietrich, Franciele, et al.
(author)
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Dexamethasone Enhances Achilles Tendon Healing in an Animal Injury Model, and the Effects Are Dependent on Dose, Administration Time, and Mechanical Loading Stimulation
- 2022
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In: American Journal of Sports Medicine. - : Sage Publications Inc. - 0363-5465 .- 1552-3365. ; 50:5, s. 1306-1316
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Journal article (peer-reviewed)abstract
- Background: Corticosteroid treatments such as dexamethasone are commonly used to treat tendinopathy but with mixed outcomes. Although this treatment can cause tendon rupture, it can also stimulate the tendon to heal. However, the mechanisms behind corticosteroid treatment during tendon healing are yet to be understood. Purpose: To comprehend when and how dexamethasone treatment can ameliorate injured tendons by using a rat model of Achilles tendon healing. Study Design: Controlled laboratory study. Methods: An overall 320 rats were used for a sequence of 6 experiments. We investigated whether the drug effect was time-, dose-, and load-dependent. Additionally, morphological data and drug administration routes were examined. Healing tendons were tested mechanically or used for histological examination 12 days after transection. Blood was collected for flow cytometry analysis in 1 experiment. Results: We found that the circadian rhythm and drug injection timing influenced the treatment outcome. Dexamethasone treatment at the right time point (days 7-11) and dose (0.1 mg/kg) significantly improved the material properties of the healing tendon, while the adverse effects were reduced. Local dexamethasone treatment did not lead to increased peak stress, but it triggered systemic granulocytosis and lymphopenia. Mechanical loading (full or moderate) is essential for the positive effects of dexamethasone, as complete unloading leads to the absence of improvements. Conclusion: We conclude that dexamethasone treatment to improve Achilles tendon healing is dose- and time-dependent, and positive effects are perceived even in a partly unloaded condition.
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- Eliasson, Pernilla, et al.
(author)
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Unloaded rat Achilles tendons continue to grow, but lose viscoelasticity
- 2007
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In: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 103:2, s. 459-463
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Journal article (peer-reviewed)abstract
- Tendons can function as springs and thereby preserve energy during cyclic loading. They might also have damping properties, which, hypothetically, could reduce risk of microinjuries due to fatigue at sites of local stress concentration within the tendon. At mechanical testing, damping will appear as hysteresis. How is damping influenced by training or disuse? Does training decrease hysteresis, thereby making the tendon a better spring, or increase hysteresis and thus improve damping? Seventy-eight female 10-wk-old Sprague-Dawley rats were randomized to three groups. Two groups had botulinum toxin injected into the calf muscles to unload the left Achilles tendon through muscle paralysis. One of these groups was given doxycycline, as a systemic matrix metalloproteinase inhibitor. The third group served as loaded controls. The Achilles tendons were harvested after 1 or 6 wk for biomechanical testing. An increase with time was seen in tendon dry weight, wet weight, water content, transverse area, length, stiffness, force at failure, and energy uptake in all three groups (P < 0.001 for each parameter). Disuse had no effect on these parameters. Creep was decreased with time in all groups. The only significant effect of disuse was on hysteresis (P = 0.004) and creep (P = 0.007), which both decreased with disuse compared with control, and on modulus, which was increased (P = 0.008). Normalized glycosaminoglycan content was unaffected by time and disuse. No effect of doxycycline was observed. The results suggest that in growing animals, the tendons continue to grow regardless of mechanical loading history, whereas maintenance of damping properties requires mechanical stimulation.
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- Hammerman, Malin, 1984-
(author)
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Tendon Healing : Mechanical Loading, Microdamage and Gene Expression
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Mechanical loading and the inflammatory response during tendon healing might be important for the healing process. Mechanical loading can improve the healing tendon but the mechanism is not fully understood. The aim of this thesis was to further clarify the effect of mechanical loading on tendon healing and how mechanical loading affects the inflammatory response during the healing process.We used a rat Achilles tendon model to study healing. The rats were exposed to different degrees of loading by unloading methods such as paralysis of the calf muscles with Botox, tail suspension, and an orthosis (a boot). Full loading was achieved by free cage activity or treadmill walking. Microdamage in tendons, unloaded with Botox, was also investigated by needling. The healing tendons were evaluated in a materials testing machine (to analyze the mechanical properties), by gene expression analysis (microarray and PCR), or histology.Our results show that moderate loading (unloading with Botox) improves the mechanical properties of healing tendons compared to minimal loading (unloading with Botox in combination with tail suspension or a boot), especially the material properties. In accordance to these findings, expression of extracellular matrix genes were also increased by moderate compared to minimal loading.Full loading improved all mechanical properties and the expression of extracellular matrix genes was further increased compared to moderate loading. However, structural properties, such as the strength and the size of the healing tendon, were more affected by full loading. Full loading also affected the expression of inflammation-related genes during the early healing phase, 3 and 5 days after tendon injury, and increased the number of immune cells in the healing tendon tissue. Also microdamage of the healing tendon (detected by blood leakage) was increased by full loading compared to moderate loading during the early healing phase.Induced microdamage by repeated needling in the healing tendon tissue increased the structural properties of the healing tendon. The gene expression after needling was similar to the gene expression after full loading.The improvement of mechanical properties by loading in healing tendons was decreased by an anti-inflammatory drug called parecoxib, which decreases the production of prostaglandins by inhibiting COX-2 activity. The effect of parecoxib was reduced when loading was reduced but we could not confirm that the effect of parecoxib was related to the degree of loading. However, parecoxib abolished the stimulatory effect of microdamage.In conclusion, these studies show that moderate loading improves the quality of the healing tendon whereas full loading also increases the quantity of the healing tendon tissue. Full loading creates microdamage and increases inflammation during the early healing phase. The strong effect of full loading on the structural properties might be due to microdamage. Indeed, the anti-inflammatory drug parecoxib seems to impair mechanical stimulation of healing tendons by reducing the response to microdamage.
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| 8. |
- Olsson, Peter, et al.
(author)
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Minnesteckningar över avlidna ledamöter 2010. Särtryck ur KVVS Årsbok 2011
- 2011
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In: Kungl. Vetenskaps- och Vitterhets-Samhället i Göteborg (KVVS).
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Journal article (other academic/artistic)abstract
- Minnesteckningar. Kungl. Vetenskaps- och Vitterhets-Samhället - ledamöter avlidna 2010. Bengt Holmberg, Gunilla Åkerström-Hougen, Gunnar Harling, Jan S. Nilsson, Ulf Lagerkvist, Erik Frykman, Sigvard Rubenowitz
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| 9. |
- Rendek, Zlatica, et al.
(author)
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Early Tensile Loading in Nonsurgically Treated Achilles Tendon Ruptures Leads to a Larger Tendon Callus and a Lower Elastic Modulus : A Randomized Controlled Trial
- 2022
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In: American Journal of Sports Medicine. - : Sage Publications Inc. - 0363-5465 .- 1552-3365. ; 50:12, s. 3286-3298
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Journal article (peer-reviewed)abstract
- Background: Early tensile loading improves material properties of healing Achilles tendon ruptures in animal models and in surgically treated human ruptures. However, the effect of such rehabilitation in patients who are nonsurgically treated remains unknown. Hypothesis: In nonsurgically treated Achilles tendon ruptures, early tensile loading would lead to higher elastic modulus 19 weeks after the injury compared with controls. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Between October 2015 and November 2018, a total of 40 nonsurgically treated patients with acute Achilles tendon rupture were randomized to an early tensile loading (loaded group) or control group. Tantalum bead markers were inserted percutaneously into the tendon stumps 2 weeks after the injury to allow high-precision measurements of callus deformation under mechanical testing. The loaded group used a training pedal twice daily to produce a gradual increase in tensile load during the following 5 weeks. Both groups were allowed full weightbearing in an ankle orthosis and unloaded range of motion exercises. Patients were followed clinically and via roentgen stereophotogrammetric analysis and computed tomography at 7, 19, and 52 weeks after the injury. Results: The mean +/- standard deviation elastic modulus at 19 weeks was 95.6 +/- 38.2 MPa in the loaded group and 108 +/- 45.2 MPa in controls (P = .37). The elastic modulus increased in both groups, although it was lower in the loaded group at all time points. Tendon cross-sectional area increased from 7 weeks to 19 weeks, from 231 +/- 99.5 to 388 +/- 142 mm(2) in the loaded group and from 188 +/- 65.4 to 335 +/- 87.2 mm(2) in controls (P < .001 for the effect of time). Cross-sectional area for the loaded group versus controls at 52 weeks was 302 +/- 62.4 mm(2) versus 252 +/- 49.2 mm(2), respectively (P = .03). Gap elongation was 7.35 +/- 13.9 mm in the loaded group versus 2.86 +/- 5.52 mm in controls (P = .27). Conclusion: Early tensile loading in nonsurgically treated Achilles tendon ruptures did not lead to higher elastic modulus in the healing tendon but altered the structural properties of the tendon via an increased tendon thickness. Registration: NCT0280575 (ClinicalTrials.gov identifier).
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