Platelet Rich Plasma (PRP) Matrix Grafts
Platelet Rich Plasma (PRP) grafting techniques are now being utilized in musculoskeletal medicine with increasing frequency and effectiveness. Soft tissue injuries treated with PRP include tendonopathy, tendonosis, acute and chronic muscle strain, muscle fibrosis, ligamentous sprains, and joint capsular laxity. PRP has also been utilized to treat intra-articular injuries. Examples include arthritis, arthrofibrosis, articular cartilage defects, meniscal injury, and chronic synovitis or joint inflammation.
Platelet Rich Plasma was first used in cardiac surgery by Ferrari et al. in 1987 as an autologous transfusion component after an open heart operation to avoid homologous blood product transfusion.1 It is now being utilized by musculoskeletal (MSK) providers following the effective use in multiple specialties. PRP has also been successfully used in various specialties such as maxillofacial, cosmetic, spine, orthopedic, podiatric and for general wound healing.2,3
MSK practitioners began using PRP for tendonosis and tendonitis in the early 1990s.4 PRP techniques have most commonly been applied by MSK practitioners previously trained in the use of—and on the knowledge backbone of—prolotherapy. Although there is a paucity of well designed, randomized trials for its use in MSK medicine, animal studies, case reports, and anecdotal evidence suggests that this technique will continue to develop as a way to regenerate tissue that has lost its inherent homeostasis and thereby relieve associated pain and dysfunction.
Standardizing the Nomenclature for PRP
The authors define a PRP Matrix Graft as follows:
A tissue graft incorporating autologous growth factors and/ or autologous undifferentiated cells in a cellular matrix whose design depends on the receptor site and tissue of regeneration.
In reading the literature, different verbiage will arise, such as platelet leukocyte gel, platelet rich plasma gel, platelet concentrate, blood plasma therapy, etc. When examining the literature, one must evaluate whether concentrations of platelets, nucleated cells, growth factors, fibrin, and platelet activation is measured. These factors— along with skillful percutaneous injection and surgical techniques—all contribute to the effectiveness of therapy.5 Everts, on reviewing 28 human studies, found that seven showed either no benefit or negative effects of PRP.3 However, when these studies were reviewed, many had very small sample sizes (as few as three patients) and several had platelet portions that had been activated prior to use via differing means. Hopefully, in the near future, the nomenclature will benefit from some form of standardization. It is the authors’ experience, however, that the wording of ‘graft’ is required in the nomenclature for third party reimbursement reasons, as well as to accurately describe how this modality is actually utilized at present in the clinic and surgical settings.
For our purposes, we will consider PRP gel as PRP that is activated with either autologous thrombin and calcium, bovine thrombin and calcium, or thrombin alone. Autologous PRP gel stipulates the use of autologous thrombin. The author considers a PRP Matrix Graft to include gel or no gel. This must be stipulated at the time of treatment. Again, the tissue of treatment will demand what matrix, if any, is added or utilized.
Constituents and Properties of an Effective Regenerative Graft
Normal tissue homeostasis is maintained in a prescribed physiologic manner. These stages will be reviewed from a hypothetical time of injury through the healing phase to understand how to maximize PRP graft matrix preparation. Platelets contain two unique types of granules—the alpha-granules and dense granules.
Alpha-granules contain a variety of hemostatic proteins (coagulation proteins), as well as growth factors, cytokines, chemokines (pro-inflammatory activation-inducible cytokines) and other proteins such as adhesion proteins.6 Of primary interest to the clinician are the three adhesion molecules and seven growth factors present in the alpha granule.7
Dense granules contain factors that promote platelet aggregation (ADP, calcium, serotonin). Cell activation of platelets causes the discharge of granule contents. In other words, platelets require activation in order to begin the cascade of events that lead to collagen restoration and growth. This activation must occur at the tissue level (where the platelets aggregate and adhere to collagen at the site of grafting).5
A synopsis of the various growth factors in PRP, together with their source and function, is presented in Table 1.
A PRP Matrix Graft is made in a clinical or operative setting by using one of the several available table-top machines on the market. Several authors offer reviews of available graft preparation centrifuges and their ability to concentrate growth factors.2,3,8 Each machine has a separate, disposable unit that concentrates platelets in a small amount of plasma. A thin layer of platelets is found immediately above the leukocytes in the buffy coat of centrifuged blood. When a concentrated platelet portion is made, the buffy coat containing elevated levels of leukocytes—along with concentrated platelets—are suspended in a small amount of plasma for subsequent grafting. The clinician hopes that the platelets are not activated and remain suspended until grafting and contact with thrombin or collagen occurs.
Necessary Stages of Healing
Normal platelet activation leads to three necessary stages of healing: Inflammation, Proliferation, and Remodeling.9 The cellular components involved in the three phases of healing are depicted in Figure 1. If any of these stages are incomplete—or if they proceed unabated—tissue homeostasis is lost and pain and loss of function may result. Most reviews on this topic focus on only the growth factors contained within the alpha granule of the platelet which is released upon platelet activation. It is important to understand, however, that if the platelets aren’t suspended with biologic levels of other constituents of plasma—such as leukocytes, cytokines, and fibrin (the matrix)—the graft is either not effective or less effective.3 If fibrin levels are too high, or platelet activation occurs prior to collagen binding, the graft is also inhibited. Other functions of platelet activation and the subsequent cascade of events that occur include cytokine signaling, chemokine release, and mitogenesis.9