• Adam Whatley

The Biological Use of Platelet-Rich Plasma (PRP) in Skeletal Muscle Injury and Repair

The Biologics of PRP and Injury Treatment

Platelet-rich plasma (PRP) is an autologous blood product that contains superimposed physiologic concentrations of platelets and other healing cells. PRP is a very popular treatment used within musculoskeletal medicine and orthopaedics for pain control and tissue regeneration.


Two main types of PRPs are used, leukocyte-poor PRP (LP-PRP) and leukocyte-rich PRP (LR-PRP). Within PRP preparation, blood is drawn from a patient and then processed by a valid PRP preparation kit, which typically includes required centrifugation (figure 1). PRP was originally used to treat low platelet levels and was then applied in oral-maxillofacial surgery which was found to improve bone healing and regeneration. Because of the positive effect seen on bone and tissue, it was investigated for regenerative purposes in orthopaedic surgery and has since been used in sports medicine, dentistry, cardiac surgery, pediatric surgery, gynecology, urology, plastic surgery, ophthalmology, and of course dermatology & hair loss treatment.Further investigation in to the interest of PRP for tissue healing and regeneration a study in the 1990s, discovered that platelets increased the proliferation of osteoblast-like cells through the release of growth factors. This supraphysiologic concentration of platelets leads to a release of growth factors in normal physiologic proportions, which has since been shown to promote healing by inducing the coagulation cascade, angiogenesis (new blood vessel formation), proliferation and differentiation of resident stem cells. More recently, a study indicated that the platelets facilitate tissue healing with stem cells by mitochondrial transfer and metabolic reprogramming. In addition to its regenerative potential, PRP is an autologous blood product that has few adverse effects and is generally considered simple and safe. Because of the ease of PRP treatment and delivery, along side safety, PRP has now been explored as a treatment option for pain relief and the regeneration of many tissue types and pathologies in orthopaedics.


PRP knee injection Birmingham

Figure 1. The process of platelet-rich plasma (PRP). Firstly, the patient’s blood is drawn and undergoes centrifugation to separate the blood cells. Blood separates into layers: the plasma, buffy layer, and red blood cells.

Platelet Activation and Growth Factors

The mechanism by which PRP works has been heavily researched and is primarily due to the release of growth factors from platelets. These growth factors facilitate healing and tissue regeneration by influencing cell migration, proliferation, differentiation, and extracellular matrix (ECM) synthesis. These main growth factors released from the PRP include fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), tissue growth factor beta (TGF-β), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF).

Because of the short lifespan of growth factors, PRP should be used with an activator to increase growth factor content, 2 common forms being calcium chloride or gluconate.



Platelet Exosomes

In addition to the growth factors, a good potential explanation for the role of PRP in tissue repair and regeneration is the ability of exosomes to influence gene expression of nearby cells (Figure 2). It has been found that exosomes isolated from PRP has accelerated tissue injury recovery, evidenced by an increase in centrally nucleated fibers and increased myogenin. In addition to increasing repair and recovery, exosomes have also been found to prevent glucocorticoid-induced cell death. The ability of exosomes to induce changes similar to those seen in PRP suggests that exosomes may play a major role in the PRP function.



PRP treatment and exosomes


Figure 2. The process of exosome release and exosome contents.

PRP and Biological Contents

LR-PRP has been shown to release more growth factors, including proinflammatory cytokines. This form of PRP treatment has been shown to improve tendon injury, and LP-PRP has been shown to slow the progression of osteoarthritis. Furthermore, it has been that this form may be desired for treatment of injuries that require increased angiogenesis (blood vessel formation) and healing, including muscle and tendon. This being said, both forms of PRP have been found to provide many similar benefits, with minimal side effects, reduced pain levels, and improved function. Table below summarises the pros and cons for both.



Different types of PRP treatment

It is imperative that preparation of PRP is done correctly. It has been found that using different preparation methods and PRP products has varied significantly in their contents, including final volumes, platelet concentrations, growth factor concentrations, and platelet activation. This variability in the composition of PRP makes it difficult to compare studies that use different preparation methods.

Biological Approaches for Muscle Injury, Repair & Regeneration

Considering the complexity of tissue healing and repair, PRP has been developed and used therapeutically to promote and facilitate the body’s natural repair process to injury and damage via modulating gene expression, inflammation, cell death and regeneration.

Broadly speaking, muscle injuries can be broken down into 2 categories - traumatic injuries and contraction-induced muscle injuries. It has previously been revealed that the mechanism of muscle injury influences differential gene expression, this being said, the healing process still involves the same events, although the healing results can vary.


Muscle Tissue Injury Healing

The natural process of muscle damage and repair involves destruction, regeneration and remodeling of cells and their surrounding environment (Figure 3). Skeletal muscle repair and remodeling is defined by initial stem cell proliferation into myoblasts (muscle cells) which then further develop into myofibers. A severe muscle injury can sometimes result in pathological healing, such as a fibrous scar or bone formation. A hematoma will form and provide a fibrin network in the early stages of scar formation. The requirement of adequate oxygen supply is met by the injury site.



Prp injury treatment

Figure 3. Timeline of muscle healing and a treatment strategy of platelet-rich plasma (PRP) in muscle healing and repair.

Improper Healing and Fibrosis Formation From Muscle Injury

Despite the natural process to muscle injury, fibrosis is a pathological process that negatively affects tissue healing and function. It also increases susceptibility for further damage. It is worth noting that the extent to which fibrosis occurs is greater in the context of immobilisation of the injury site and surrounding structures, meaning early mobilisation can reduce negative effects. Considering the negative implications of fibrosis on tissue healing, function, mobility, and risk for reinjury, it is critical to be able to facilitate pathological fibrosis in the process of proper tissue healing. However, the application of PRP alone or combined with other agents can greatly reduce fibrous scars in muscle injuries.


PRP Clinical Applications in Muscle Healing

PRP in Pain Relief There has been increasing interest in the effectiveness of PRP injection treatment on different injuries. One benefit is pain reduction. Pain from muscle injury is initiated from the proinflammatory mediators during muscle healing, such as TNF-α, IL-1, IL-6, and substance P. PRP is able to regulate those inflammatory mediators, which can reduce pain caused from inflammation. The mechanism behind the beneficial effects of PRP is thought to start by expediting the inflammation phase. Platelet contents are released, attracting leukocytes, neutrophils, macrophages, and fibroblasts to the injury site to clear debris and facilitate healing. Clinically, this would result in decreased pain, allowing individuals to recover faster from injury.


A recent meta-analysis by Grassi et al investigating the effectiveness of PRP for acute muscle injuries included various studies identifying pain reduction, especially in the first 3 weeks. Sheth et al performed a meta-analysis on randomised controlled trials performed from 2013 to 2016 and concluded that PRP injection treatments significantly reduced the time to return to sports without increasing the risk of reinjury. The reduction in pain, then allows earlier range of motion and recovery.

Accelerating Muscle Regeneration

Muscle, healing, repair, regeneration and prevention of scar tissue is the ultimate goal of treatment of acute muscle injury, this following by corrective exercise and preventative strengthening. Currently, PRP is used to promote differentiation required to produce new muscle tissue to facilitate healing and repair. Faster muscle regeneration and prevention of fibrosis through a series of engineered PRP injections has been shown to promote toward faster recovery and return of function. Clinical applications of engineered PRP injections could be applied to any acute muscle injury, followed by corrective rehabilitation and strengthening.


Improving Functional Repair via Vascularisation and Innervation

In order for PRP to be an effective treatment, the regenerated muscle must be healthy and functional. Therefore, the ability of PRP injections to induce active repair after muscle injury relies on its ability to promote the regeneration of vessels and nerves to this new tissue. Repair of any tissue requires adequate nutrients, inflammatory cells, and growth factors, which are provided by the blood. Furthermore, muscle requires innervation to prevent wasting/atrophy and degeneration. Another greatly appreciated benefit of PRP treatment is the increased concentration of growth factor VEGF, responsible for angiogenesis (New blood vessel formation). Increased blood vessel and blood supply of damaged tissue leads to improved repair and improved function.


There has also been interest in the effect of PRP in nerve regeneration, specifically in nerve grafting in plastic surgery. Research found that PRP increased the number of myelinated nerve axons and could play a role in nerve regeneration. Adequate innervation of the skeletal muscle after injury is necessary to regain functional repair and could be an additional clinical application of PRP treatment



In summary

PRP treatment has been of great focus of recent research in regenerative medicine and has been widely used in clinical practice in many different areas. The huge benefit of PRP treatment with in medical specialisms is its autologous use requires minimal resources, and it is a relatively simple procedure to perform with minimal side-effects and complications. There are many studies that have investigated the mechanisms behind PRP, which suggest growth factors and active proteins could have a major effect in repairing injured tissues as well as reducing inflammation and relieving pain. The functional promotion of tissue repair and regeneration of PRP has been evaluated in many studies. and continues to see ongoing benefits within muscle repair, healing and regeneration. In the recent review below, they discussed some of the more recent studies in the basic science behind PRP as well as the beneficial application within musculoskeletal medicine – orthopaedics and sports medicine. The application of PRP in muscle injury and repair has been well investigated, specifically its role in stimulating muscle regeneration and controlling pain, and research in this area will further develop so PRP treatment can be taken advantage of with regards to the basic science principles.



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