Current Concepts With Video Illustrations
Platelet-Rich Plasma: A Milieu of Bioactive Factors

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Abstract

Platelet concentrates such as platelet-rich plasma (PRP) have gained popularity in sports medicine and orthopaedics to promote accelerated physiologic healing and return to function. Each PRP product varies depending on patient factors and the system used to generate it. Blood from some patients may fail to make PRP, and most clinicians use PRP without performing cell counts on either the blood or the preparation to confirm that the solution is truly PRP. Components in this milieu have bioactive functions that affect musculoskeletal tissue regeneration and healing. Platelets are activated by collagen or other molecules and release growth factors from alpha granules. Additional substances are released from dense bodies and lysosomes. Soluble proteins also present in PRP function in hemostasis, whereas others serve as biomarkers of musculoskeletal injury. Electrolytes and soluble plasma hormones are required for cellular signaling and regulation. Leukocytes and erythrocytes are present in PRP and function in inflammation, immunity, and additional cellular signaling pathways. This article supports the emerging paradigm that more than just platelets are playing a role in clinical responses to PRP. Depending on the specific constituents of a PRP preparation, the clinical use can theoretically be matched to the pathology being treated in an effort to improve clinical efficacy.

Section snippets

PRP Production

PRP is a plasma suspension that contains all components of whole blood in varying amounts (Videos 1 and 2, available at www.arthroscopyjournal.org). According to the Red Cross, PRP by definition contains a minimum of 200,000 platelets/μL. Preparation processes take advantage of differing density gradients of the components in blood to concentrate platelets. Centrifugation of whole venous blood containing an anticoagulant results in a plasma supernatant with a gradient of cellular concentration.

Platelets

Platelets (thrombocytes) range from 2 to 3 μm in size while circulating for 7 to 10 days at concentrations of 150 to 400 × 103/μL. They are anucleate cytoplasmic fragments of multinucleated megakaryocytes located in bone marrow. Platelets are most often thought of primarily for their hemostatic and coagulation functions; however, proteomic studies have shown that platelets contain over 800 proteins with numerous post-translational modifications, such as phosphorylation, resulting in over 1,500

Plasma

Plasma is defined as the yellow-colored liquid component of blood in which blood cells are suspended. Approximately 200 proteins have been documented in plasma, including albumin, immunoglobulins, complement, and clotting factors.53 Because plasma transiently contains many proteins released from cells and metabolic processes throughout the body, the presence of as many as 679 proteins has been documented.54 Biomarkers of bone turnover can be found in plasma as well, including osteocalcin and

Leukocytes

Mammalian leukocytes are classified as granulocytes (neutrophils, eosinophils, and basophils) or mononuclear cells (lymphocytes and monocytes or macrophages). Phagocytic cells such macrophages are essential to the in vivo healing process.66 A murine model was used to show that macrophages were essential for debridement of damaged ligamentous tissue and for cytokine release that mediates the repair process.66 The presence of leukocytes can result in proinflammatory cellular signaling and local

Erythrocytes

The centrifugation process used to generate PRP typically reduces or eliminates the presence of erythrocytes (red blood cells). Because some red blood cells are often present, they are worth discussing. The main function of erythrocytes is to carry oxygen, which is essential for tissue repair. As such, red blood cells lack most cellular organelles, including a nucleus, endoplasmic reticulum, and mitochondria. They contain about 750 proteins compared with the estimated 20,000 or more proteins of

Clinical Relevance

Knowing the components of PRP being used will help elicit the important factors in various applications of this regenerative therapy (Table 4). As an example, 5 recent articles in Arthroscopy evaluated anterior cruciate ligament reconstruction and compared PRP-augmented procedures with controls.77, 78, 79, 80, 81 Magnetic resonance imaging evaluation times ranged from 3 to 24 months postoperatively, and results of these trials were variable. Several letters to the editor and the authors'

Conclusions

PRP is a useful regenerative therapy to address many musculoskeletal injuries. It is important to understand that PRP is more than just platelets and that it contains many bioactive factors that act in anabolic, catabolic, proinflammatory, and anti-inflammatory pathways. Some components are also involved in the modulation of the immune response. The precise combination and concentration of platelets, leukocytes, and other plasma components best for musculoskeletal healing are not presently

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    The authors report that they have no conflicts of interest in the authorship and publication of this article.

    Note: To access the videos accompanying this report, visit the March issue of Arthroscopy at www.arthroscopyjournal.org.

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