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Low-level mechanical stimulation is sufficient to improve tendon healing in rats
Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet.
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2012 (Engelska)Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 113, nr 9, s. 1398-1402Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Treatment of tendon injuries often involves immobilization. However, immobilization might not prevent mild involuntary isometric muscle contraction. The effect of weak forces on tendon healing is therefore of clinical interest. Studies of tendon healing with various methods for load reduction in rat Achilles tendon models show a consistent reduction in tendon strength by at least half, compared with voluntary cage activity. Unloading was not complete in any of these models, and the healing tendon was therefore still exposed to mild mechanical stimulation. By reducing the forces acting on the tendon even further, we now studied the effects of this mild stimulation. Rat Achilles tendons were transected and allowed to heal spontaneously under four different loading conditions: 1) normal cage activity; 2) calf muscle paralysis induced by botulinum toxin A (Botox); 3) tail suspension; 4) Botox and tail suspension, combined, to eliminate even mild stimulation. Healing was evaluated by mechanical testing after 8 days. Botox alone and suspension alone both reduced tendon callus size (transverse area), thereby impairing its strength compared with normal cage activity. The combination of Botox and suspension did not further reduce tendon callus size but drastically impaired the material properties of the tendon callus compared with each treatment alone. The peak force was only a fifth of that in the normal cage activity group. The results indicate that also the mild loading that occurs with either Botox or suspension alone stimulates tendon healing. This stimulation appears to affect mainly tissue quality, whereas stronger stimulation also increases callus size.

Ort, förlag, år, upplaga, sidor
American Physiological Society , 2012. Vol. 113, nr 9, s. 1398-1402
Nyckelord [en]
Achilles tendon, mechanical stress, wound healing, hindlimb unloading, immobilization
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-85847DOI: 10.1152/japplphysiol.00491.2012ISI: 000310649200007OAI: oai:DiVA.org:liu-85847DiVA, id: diva2:573290
Anmärkning

Funding Agencies|Swedish Research Council|2009-6725|Linkoping University||Ostergotland County Council||King Gustaf V and Queen Victoria Free Mason Foundation||Swedish National Center for Research in Sports||

Tillgänglig från: 2012-11-30 Skapad: 2012-11-30 Senast uppdaterad: 2018-02-20
Ingår i avhandling
1. Tendon Healing: Mechanical Loading, Microdamage and Gene Expression
Öppna denna publikation i ny flik eller fönster >>Tendon Healing: Mechanical Loading, Microdamage and Gene Expression
2018 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2018. s. 28
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1609
Nationell ämneskategori
Biomaterialvetenskap
Identifikatorer
urn:nbn:se:liu:diva-145281 (URN)10.3384/diss.diva-145281 (DOI)9789176853610 (ISBN)
Disputation
2018-03-26, Belladonna, Campus US, Linköping, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2018-02-20 Skapad: 2018-02-20 Senast uppdaterad: 2018-02-28Bibliografiskt granskad

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Andersson, ThereseEliasson, PernillaHammerman, MalinSandberg, OlofAspenberg, Per

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Andersson, ThereseEliasson, PernillaHammerman, MalinSandberg, OlofAspenberg, Per
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Institutionen för klinisk och experimentell medicinHälsouniversitetetOrtopediOrtopedkliniken i Linköping
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