Effect of platelet-rich plasma on rat Achilles tendon healing is related to microbiota

Abstract

Background and purposeIn 3 papers in Acta Orthopaedica 10 years ago, we described that platelet-rich plasma (PRP) improves tendon healing in a rat Achilles transection model. Later, we found that microtrauma has similar effects, probably acting via inflammation. This raised the suspicion that the effect ascribed to growth factors within PRP could instead be due to unspecific influences on inflammation. While testing this hypothesis, we noted that the effect seemed to be related to the microbiota.Material and methodsWe tried to reproduce our old findings with local injection of PRP 6 h after tendon transection, followed by mechanical testing after 11 days. This failed. After fruitless variations in PRP production protocols, leukocyte concentration, and physical activity, we finally tried rats carrying potentially pathogenic bacteria. In all, 242 rats were used.ResultsIn 4 consecutive experiments on pathogen-free rats, no effect of PRP on healing was found. In contrast, apparently healthy rats carrying Staphylococcus aureus showed increased strength of the healing tendon after PRP treatment. These rats had higher levels of cytotoxic T-cells in their spleens.InterpretationThe failure to reproduce older experiments in clean rats was striking, and the difference in response between these and Staphylococcus-carrying rats suggests that the PRP effect is dependent on the immune status. PRP functions may be more complex than just the release of growth factors. Extrapolation from our previous findings with PRP to the situation in humans therefore becomes even more uncertain.

Depletion of cytotoxic (CD8+) T cells impairs implant fixation in rat cancellous bone

“…Seven and 12 days after surgery, the animals were killed, and their tendons harvested together with the calcaneal bone and muscles. The tendon was fixed in clamps by the muscle and the calcaneal bone, and the methods for mounting have been described elsewhere . The tendon was then pulled apart with a cross‐head speed of 0.1 mm/s while the force and displacement were measured.…”

“…The complete procedure has been described elsewhere. 9 Briefly, the skin was incised to expose the Achilles tendon before it was completely transected and left unsutured. Furthermore, the plantaris tendon was removed.…”

“…The tendon was fixed in clamps by the muscle and the calcaneal bone, and the methods for mounting have been described elsewhere. 9 The tendon was then pulled apart with a cross-head speed of 0.1 mm/s while the force and displacement were measured. Force-at-failure, stiffness, and energy uptake were acquired from the generated force-displacement curve.…”

Concise Review: Stem Cell Fate Guided By Bioactive Molecules for Tendon Regeneration

“…Another important approach in treating ligament and skeletal muscle injuries is the use of endogenous platelet rich plasma (PRP) [11], which was recently demonstrated to promote the proliferation and myogenic differentiation of myoblasts in vitro when combined with a TGF-b inhibitor [12]. However, controversial conclusions and variable clinical outcomes following PRP treatment for tendon repair have been reported [13][14][15]. Additionally, variability in the preparation and composition of PRP makes it difficult to compare results across studies [16].…”

Response to mechanical loading in rat Achilles tendon healing is influenced by the microbiome

“…Tendon healing is dependent on the immune system [1] which has a profound effect on the strength of the tendon callus [2,3]. The immune system, and particularly T cells, changes in response to alterations in the microbial environment in the gut and skin [4,5].…”