Background Blood platelets release a cocktail of growth factors when activated, some of which are thought to initiate and stimulate repair.Experiment and findings We studied whether a platelet concentrate injection would improve Achilles tendon repair in an established rat model. The Achilles tendon was transected and a 3 mm segment removed. After 6h, a platelet concentrate was injected percutaneously into the hematoma. This increased tendon callus strength and stiffness by about 30% after 1 week, which persisted for as long as 3 weeks after the injection. At this time, the mechanical testing indicated an improvement in material characteristics-i.e., greater maturation of the tendon callus. This was confirmed by blinded histological scoring.Interpretation Platelet concentrate may prove useful for the treatment of Achilles tendon ruptures.

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The results suggest that cyclooxygenase-2 inhibitors should be used with care in the early period after tendon injury.

BackgroundPlatelet concentrate application with added thrombin improves Achilles tendon repair in the rat. Upon tissue injury, platelets are activated by thrombin, which has many biological properties in common with growth factors. We wanted to differentiate the effect of platelets from that of thrombin.Methods The Achilles tendon was transected in 50 rats. Platelet gel was prepared from the blood of 10 other rats. The rats were given either platelet gel with active or neutralized thrombin implanted into the defect during the operation, or a local injection 6h postoperatively with 50 µL of either platelet concentrate, thrombin or saline. The rats were killed after 14 days and the tendons were mechanically tested.Results Compared to saline, platelet gel caused a 42% increase in force at failure, a 90% increase in energy, and a 61% increase in ultimate stress. Platelet gel with neutralized thrombin caused a 22% increase in force at failure, and energy and stress were less elevated. Injected platelet concentrate caused a 24% increase in force at failure, and thrombin caused a 10% increase. These effects and the differences between treatments were statistically significant. Interpretation Platelets and thrombin had independent and additive stimulatory effects on tendon repair. The clinical relevance is so far unknown.

This study examines the hypothesis that cartilage-derived morphogenic protein-2 (CDMP-2) can improve tendon healing after surgical repair. We have previously found improved tendon healing by applying CDMP-2 in models for conservative treatment with mechanically loaded Achilles tendon defects in rats and rabbits. In this study, the patellar tendon was unloaded by patello- tibial cerclage and cut transversely in 40 rabbits. Two hours post-operative, the rabbits received a dose of 20 microg of CDMP-2 or vehicle injected into the hematoma. Specimens were harvested after 14 and 28 days and evaluated by biomechanical testing, radiography and histology. At 14 days, CDMP-2 caused a 65% increase in force at failure, a 50% increase in ultimate stress and a 57% increase in stiffness, as compared with controls. There was no effect on callus size. At 28 days, no differences between the treatment groups could be demonstrated. No bone or cartilage was found in any tendon or regenerated tissue at any time point. Thus, early tendon repair can be stimulated by CDMP-2 in an unloaded model. These results suggest that CDMP-2 might be of interest for clinical use as a complement to surgical treatment of tendon ruptures.

Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair. Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed. Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections. Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors.

Results are compatible with a positive effect of CDMP-2, but the power was too low to demonstrate any such effect. Considering that spontaneous ruptures in humans are likely to have a more variable geometry than in this model, humans can also be expected to vary a lot in early mechanical characteristics. This emphasizes the importance of individualized rehabilitation programs. The low hysteresis suggests that the energy storing capacity is rather easy for the tissues to develop; possibly it is harder to create appropriate energy dissipation, in order to avoid re-rupture.