Platelet rich plasma in osteoarthritis: More than a growth factor therapy

Abstract

Osteoarthritis (OA) is the most commonly encountered degenerative joint disorder in clinical medicine and the pain and stiffness caused by osteoarthritis represents a leading cause of physical disability in individuals of retirement age. Treatment options for OA patients are limited and largely targeted to pain management. Such is the mechanism behind the most commonly prescribed OA therapies including acetaminophen, NSAIDs, opioids, and steroids. However, these palliative pain management tools do not address the underlying pathophysiology of OA disease. This leaves a significant clinical unmet need for disease modifying OA therapies. Growth factor therapies and regenerative medicine strategies are emerging as promising alternatives to palliative care because these treatments bring significant potential to control chronic inflammation, enhance cartilage repair, and restore other joint tissues to a healthy state. Interestingly, a Clinicaltrials.gov search using the terms "osteoarthritis" and "growth factor" identified 43 relevant studies. Of these, only 26% used growth factor therapies directly, including FGF-18, BMP-2, and transgenic human chondrocytes producing TGF-β1. 23% of the studies were dedicated to inhibitors of NGF. The overwhelming majority of studies (47%) used autologous blood products, especially platelet rich plasma (PRP), which constituted 33% of the total studies. This was interesting because although platelets in PRP do indeed harbor large quantities of different growth factors that can affect the status of the treated tissue, growth factors represent only a single aspect of the bioactivity of platelets. Furthermore, platelets represent only one aspect of the potential bioactivity of PRP. Depending upon the methods used for PRP generation, it may also contain other physiologically important components of the whole blood from which it is derived. Recent studies indicate non-platelet components of whole blood such as red blood cells and leukocytes are essential for normal platelet function, including growth factor release. Therefore, this narrative review discusses PRP from a physiological context that explores beyond platelet growth factors to encompass and illuminate roles of non-platelet cells in the bioactivity of PRP, and how these additional mechanisms lead to the conclusion that PRP can be much more than a growth factor therapy.

Leukocyte-rich PRP for knee osteoarthritis: Current concepts

“…22 It has grown ever since and been applied to the fields of orthopaedics, dermatology, plastic surgery, odontology and even veterinary medicine. 23 This biological product derived from autologous blood centrifugation contains a mixture of a variety of cells with a primary focus on concentrated platelets above baseline 24,25 and is obtained via the use of commercial kits or in house techniques, resulting in different PRP products and, therefore, different terminologies. 23 The platelets present in PRP contain granules with a broad range of active biomolecules which, upon activation, release these biomolecules, therefore stimulating the natural healing cascade.…”

Platelet-Rich Plasma Power-Mix Gel (ppm)—An Orthobiologic Optimization Protocol Rich in Growth Factors and Fibrin

“…PRP is defined as an autologous preparation obtained from the centrifuged peripheral blood of patients with a concentration that is 2-5 times greater than the basal concentration [38][39][40][41]. This orthobiologic product can be processed manually or with the assistance of commercial kits; however, since there are many different protocols in the literature there is a lack of consensus regarding an idealistic preparation of PRP.…”

“…The benefits associated with PRP therapy, for example, were long believed to be only a result of the relative abundance of growth factors and their individual biological roles (Table 2). However, further research showed that PRP also promoted important secondary effects, including inflammatory modulation [38,[57][58][59][60], anticatabolic activity [61], normalization of integral autophagy [62,63], cytokine regulation [64][65][66], and pro-anabolic stimuli [67][68][69]. More importantly, it is also directly involved in fibrinolytic reactions, which are a key step in the resolution of tissue injury [70].…”