The cellular environment in which platelet-rich preparations are placed strongly influences the direction and magnitude of tissue response. In orthopedics, the majority of PRP research has focused on its effects on connective tissues such as the tendon, ligament, and muscle. Healing is classically defined as a complex and dynamic process resulting in the restoration of anatomic continuity and function. In general, it can be separated into three phases: inflammation, proliferation, and remodeling [44].

The initial inflammatory phase can last up to 72 h, involves a number of inflammatory responses, and is usually characterized by pain, swelling, redness, and increased local temperature. It is also defined by hemostasis, with platelets establishing clot formation, and the release of growth factors that aid in activating and attracting inflammatory cells like neutrophils and macrophages to the site of injury. The proliferation phase, which lasts from 48 h up to 6 weeks, is characterized by the construction of an extracellular matrix associated with granulation, contraction, and epithelialization. Finally, the remodeling phase, lasts from 3 weeks up to 12 months, is defined by collagen remodeling, leading to an increase in the functional capabilities of the injured tissues. The physiologic progression through these phases of wound healing is orchestrated by growth factors and cytokines, many of which are released and modulated by blood components in PRP [45–47].

With the exception of muscle complete ruptures/avulsions, complications (like myositis ossificans), and the persistence of uncomfortable symptoms in chronic injuries, almost all the acute muscle damages are usually treated nonsurgically. Experimental and clinical studies demonstrate that myogenesis is not restricted only to the prenatal period but may also occur during the healing after a muscle tissue damages [48].

In the literature, many studies have shown beneficial effect with the use of PRP in traumatic muscle pathologies. The proposed mechanisms, with in vitro and in vivo assessments, include an increase of activation of satellite cells improving the diameter of regenerating fibers and the enhancement of the myogenesis and healing response.

For example, in an experimental in vitro model conducted on the gastrocnemius muscle of rats, Wright-Carpenter et al. observed accelerated activation of satellite cells, 30–48 h after injury, and an increase in the diameter of the muscle fibers undergoing regeneration, during the first week after injury [49].

The authors also observed an increased concentration of FGF-2 (460%) and TGF-beta1 (82%) through ELISA testing and suggested that these could have been responsible for the accelerated regeneration, due to the proliferative and chemotactic characteristics. In the same way, Hammond et al., analyzing major eccentric injuries of the anterior tibial muscle of rats, observed that the time taken for muscle regeneration was significantly shorter in the group treated with PRP. This paper suggested that acceleration of myogenesis was probably the mechanism responsible for this effect from platelet-rich plasma injections [50].

Harris et al. therefore reported, with histological evaluation, the persistence (but with a decreased amount) for a prolonged time of inflammatory infiltrated cells in muscle tissues of healthy rabbits that received PRP, but not the same result as those that received only saline solution [51].

In contrast, Gigante et al. did not note any difference regarding the inflammatory process between muscle injuries in rats treated with PRP and those that were not treated. Despite this, the authors showed an improvement of muscle regeneration and long-term vascularization in the first group [52].

However, in literature there are conflicting opinions about the use of PRP in the human muscle injuries. Wright-Carpenter et al., for example, with a retrospective, nonrandomized, and non-blinded study using autologous conditioned serum (ACS) of 18 professional sportsmen (with a variety of muscle strains), reported shorter recovery time from injury than a control group (treated with Actovegin; Nycomed, Zurich, Switzerland). ACS contains essentially activated PRP, which produces a lower yield of growth factors than most PRP [53].

In the same way, Bubnov et al. evaluated the efficacy of ultrasound-guided PRP treatment, comparing them with the traditional conservative therapy. In this randomized study, 30 patients with 34 lesions were enrolled; the authors reported faster pain relief and a greater range of motion recovery in the group of patients treated using PRP than the control group [9].

Also Zanon et al. in 2016 reported, in a case series of level IV, the advantages of the use of platelet-rich plasma injections in hamstring lesions in a large series of professional football players. With a mean follow-up of 36.6 months (range 22–42), 25 hamstring injuries (grade 2 according to MRI classification) were studied. The authors showed good/excellent results if this technique was applied not before than 24 h from the traumatic event?? meaning and using an ultrasound-guided procedure. PRP-treated lesions did not heal more quickly than untreated lesions described in the literature, but they showed a smaller scar and excellent repair tissue in a midterm follow-up [6].

Despite this, completely different results have been also published. For example, Guillodo et al. published a cohort study evaluating the time to return to play (TTRTP) in athletes with grade III acute hamstring injuries treated with one PRP injection. In this paper, only 15 of 34 patients underwent this procedure. The remaining 19 athletes were considered a control group and treated with a conservative strategy. The same standardized rehabilitation program was then used in both groups. The mean TTRTP at the pre-injury level was 50.9 ± 10.7 days in the PRP group and 52.8 ± 15.7 days in the control group. The authors did not find statistically significant differences [54].

The same conclusion was found in a double-blind placebo-controlled trial conducted in three study centers. Reurink et al. demonstrated no benefit, in patients with acute hamstring injuries, using two intramuscular PRP injections compared with placebo. In this study, the authors randomly assigned patients to receive intramuscular injections of PRP or isotonic saline (as a placebo) in 80 competitive and recreational athletes with acute hamstring muscle damage [55]. The median time until the resumption of sports activity was 42 days (interquartile range, 30 to 58) in the PRP group and 42 days (interquartile range, 37 to 56) in the placebo group. The reinjury rate was 16% in the PRP group and 14% in the placebo group.