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How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks?: Interplay between early regeneration and mechanical stimulation
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
2006 (English)In: Acta Orthopaedica, ISSN 1745-3674, Vol. 77, no 5, 806-812 p.Article in journal (Refereed) Published
Abstract [en]

Background Mechanical stimulation improves the repair of ruptured tendons. Injection of a platelet concentrate (platelet-rich plasma, PRP) can also improve repair in several animal models. In a rat Achilles tendon transection model, 1 postoperative injection resulted in increased strength after 4 weeks. Considering the short half-lives of factors released by platelets, this very late effect calls for an explanation.

Methods We studied the effects of platelets on Achilles tendon regenerates in rats 3, 5 and 14 days after transection. The tendons were either unloaded by Botulinum toxin A (Botox) injections into the calf muscles, or mechanically stimulated in activity cages. No Botox injections and ordinary cages, respectively, served as controls. Repair was evaluated by tensile testing.

Results At 14 days, unloading (with Botox) abolished any effect of the platelets and reduced the mechanical properties of the repair tissue to less than half of normal. Thus, some mechanical stimulation is a prerequisite for the effect of platelets at 14 days. Without Botox, both activity and platelets increased repair independently of each other. However, at 3 and 5 days, platelets improved the mechanical properties in Botox-treated rats.

Interpretation Platelets influence only the early phases of regeneration, but this allows mechanical stimulation to start driving neo-tendon development at an earlier time point, which kept it constantly ahead of the controls.

Place, publisher, year, edition, pages
2006. Vol. 77, no 5, 806-812 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-13014DOI: 10.1080/17453670610013033OAI: oai:DiVA.org:liu-13014DiVA: diva2:17672
Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2009-06-08
In thesis
1. Stimulation of tendon repair by platelet concentrate, CDMP-2 and mechanical loading in animal models
Open this publication in new window or tab >>Stimulation of tendon repair by platelet concentrate, CDMP-2 and mechanical loading in animal models
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Growth factor delivery may be useful to accelerate the rate of tendon healing. We studied Platelet Concentrate, which in effect can be regarded as a cocktail of growth factors relevant for tendon healing. In a rat Achilles tendon transection model, one postoperative injection of Platelet Concentrate resulted in increased strength even 3 weeks later.

Mechanical stimulation improves the repair of ruptured tendons. We studied the effects of platelets upon Achilles tendon regenerates in rats 3, 5 and 14 days after transection, either unloaded or mechanically stimulated. At 14 days, physical activity and platelets increased repair independently. Unloading decreased the mechanical properties of the repair tissue to less than half of normal. Moreover, the platelets had no effect without loading.

Thrombin, which we used for platelet activation, improved healing of the rat Achilles tendon by itself. Conversely, continuous inhibition of thrombin by low molecular weight heparin (LMWH) inhibited tendon repair. However, intermittent inhibition, similar to clinical thromboprophylaxis, had no effect on tendon healing.

Cartilage Derived Morphogenetic Protein-2 (CDMP-2) can improve tendon healing in loaded defect models. We now studied unloaded repair in a rabbit patellar tendon model. Two hours postoperative, the rabbits received CDMP-2 injected into the haematoma. The healing tendon became 65 % stronger than controls. We then studied Achilles tendon healing with CDMP-2 injections in sheep, to get a bigger animal model. There was an unexpectedly high variation of repair in these animals, and the study turned out to be underpowered. Spontaneous ruptures in humans have a more variable geometry than in our sheep model, so humans can also be expected to vary a lot in mechanical characteristics of Achilles tendon repair. This accentuates the importance of individualized rehabilitation programs.

In conclusion, both platelet concentrate and CDMP-2 injections might be of interest for clinical use as a complement to surgical or conservative treatment of tendon ruptures. Platelet treatment for tendon ruptures should probably be combined with early physiotherapy.

Place, publisher, year, edition, pages
Institutionen för nervsystem och rörelseorgan, 2007. 34 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1005
Keyword
Achilles tendon, injuries, physiology, Blood platelets, tendon injuries, physiopathology, therapy, wound healing
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-11264 (URN)978-91-85831-88-3 (ISBN)
Public defence
2007-06-07, Aulan, Hälsans Hus, Campus US, Linköpings universitet, Linköping, 13:00 (English)
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Supervisors
Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2009-08-22

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Virchenko, OlenaAspenberg, Per

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