Platelet Rich Plasma and Osteoarthritis

Platelet Rich Plasma (PRP)

According to the World Health Organization (WHO), musculoskeletal injuries are the most common cause of severe long-term pain and physical disability and affect hundreds of millions of people around the world.(1)

Osteoarthritis (OA) is  a  chronic  musculoskeletal  condition  that  commonly  affects  the  joints, especially large joints such as the knee, ankle, hip and shoulder. It is a major public health problem worldwide and is projected to rapidly increase  as  the  population  ages  and  rates  of  obesity  escalate.(2) Osteoarthritis is the most common degenerative joint disease, affecting more than 25% of the population over 18 years-old. Pathological changes seen in Osteoarthritis joints include progressive loss and destruction of articular cartilage, thickening of the subchondral bone, formation of osteophytes, variable degrees of inflammation of the synovium, degeneration of ligaments and menisci of the knee and hypertrophy of the joint capsule.(3)

Osteoarthritis causes substantial pain and disability and impacts on quality-of-life. Hip and knee Osteoarthritis has been ranked as the eleventh highest contributor to global disability and two of the highest in years lived with disability. The  disability  associated  with  Osteoarthritis  results  in  a  considerable  economic burden,  both  in  direct  costs  related  to  treatment, particularly  joint  replacement  surgery,  and job-related indirect costs, including loss of productivity. (2) Thus, as Osteoarthritis is typically progressive with symptoms and structural deterioration driving the need for joint replacement, identifying efficacious, safe treatments that address both symptoms and joint reparation is an important objective.

The traditional management of orthopaedic and sports related injuries includes everything from conservative “RICE” treatment(1) which corresponds to the acronyms of rest, ice, compression and elevation of the site of the injury(4), and physical therapy, corticosteroid injections or surgical intervention. Recently, advances in biomedicine and biotechnology have enthused the use of cell therapy, tissue engineering, and autologous blood concentrates to enhance healing and stimulate growth in bone and soft tissue injuries.(1)

One of the most popular methods used to biologically enhance healing in the fields of orthopaedic surgery and sports medicine includes the use of autologous blood products, particularly, platelet rich plasma (PRP). PRP is an autologous concentration of human platelets to supra-physiologic levels. It is produced from a patient’s peripheral vein and centrifuged to achieve a high concentration of platelets within a small volume of plasma. It is then re-injected at a site of injury or inserted as a gel or other biomaterials during surgery. (1)

What is platelet-rich plasma?

PRP is an autologous blood product that contains an elevated concentration of platelets above that of whole blood. (2) Platelets are irregularly shaped, non-nucleated cytoplasmic bodies derived from fragmentation of megakaryocyte precursors. They circulate in the blood of mammals expressing glycoproteins on their cell membranes and play a pivotal role in hemostatis and wound healing via the formation of fibrin clots.(1)

Platelet-rich plasma is produced from blood obtained by phlebotomy, which is centrifuged to achieve a high concentration of platelets within a small volume of plasma. The platelet-rich product is then re-injected at a site of injury or prepared as a gel or other biomaterial and inserted during surgery. There are numerous protocols and commercial systems for producing PRP. Traditionally, two centrifugation steps are used to isolate the erythrocyte fraction from the buffy coat (plasma containing platelets, leukocytes, and clotting factors). The second step separates the platelet-poor plasma (PPP) from the platelet-rich fraction. (1)

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PRP in the context of osteoarthritis

Osteoarthritis is a disease affecting all tissues of the joint including cartilage, bone, ligament, and muscle. It has long been considered the result of mechanical overloading causing damage to  the  joint.  However,  more recent  progress  in  molecular  biology  has  provided  new understandings  regarding Osteoarthritis  pathophysiology  in  which  inflammatory  mediators,  growth factors,  chondrocyte  apoptosis  and  imbalance  between  anabolic  and  catabolic  mechanisms play  an  important  role.  It  is  now  thought  that  inflammation  might  be  a  major  driver  of the  OA  process,  rather  than  inflammation  being  a  secondary  consequence  of  the  disease. Several  cytokines,  such  as  interleukin-1β  and  transforming  growth  factor β,  proteases  and nitric oxide synthetase all appear to be essential for cartilage degradation in the pathogenesis of Osteoarthritis. Although the biology of PRP is not completely understood, PRP may be beneficial in Osteoarthritis by interfering  with  catabolic  and  inflammatory  events  and  by  subsequently  promoting  anabolic responses. Activation of PRP releases an initial burst then a sustained release of biologically active growth   factors   and   other   molecules,   including   platelet-derived   growth   factor and  vascular  endothelial growth factor, These proteins  are responsible for a range of critical tissue healing  roles such   as   chondrocyte   apoptosis inhibition,   bone   and   vessel   remodelling,   inflammatory modulation,  and  importantly,  collagen  synthesis. Additionally,  other  bioactive molecules  released  by  platelets,  such  as  fibrin,  act  as  a  scaffold  and  chemo-attractant  for further migration of stem and other cells to the damaged tissuethat trigger a healing response. In  general,  pre-clinical  literature  provides  support  for  the ¡use  of  PRP injections to regenerate damaged joint tissue in Osteoarthritis due to its influence on the whole joint environment. In vitro studies mostlyshow a positive effect of PRP on cartilage with increases in chondrocyte proliferation  without  affecting chondrogenesisand  enhancedproduction  of type  II  collagen and  proteoglycans. Effects  on  meniscal  cells and  synoviocytes have  alsobeen  reported. In  studies  using animal  models of  Osteoarthritis,  PRP  has  been  reported  as  leading  to better  cartilage  regeneration.

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References:

1. Middleton KK, Barro V, Muller B, Terada S, Fu FH. Evaluation of the effects of platelet-rich plasma (PRP) therapy involved in the healing of sports-related soft tissue injuries. Iowa Orthop J. 2012;32:150-63.
2. Bennell KL, Hunter DJ, Paterson KL. Platelet-Rich Plasma for the Management of Hip and Knee Osteoarthritis. Curr Rheumatol Rep. mayo de 2017;19(5):24.
3. Chen D, Shen J, Zhao W, Wang T, Han L, Hamilton JL, et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res. 2017;5:16044.
4. van den Bekerom MPJ, Struijs PAA, Blankevoort L, Welling L, van Dijk CN, Kerkhoffs GMMJ. What is the evidence for rest, ice, compression, and elevation therapy in the treatment of ankle sprains in adults? J Athl Train. agosto de 2012;47(4):435-43.