Biology of PRP

  • Humans have an average baseline blood platelet count of 200,000 ± 75,000/μL
  • Platelets have an in vivo half-life of ~7-10 days
  • Platelets in circulating blood remain in a non-active state
  • Inside platelets are alpha granules, which contain cytokines, growth factors and bioactive proteins essential for tissue repair and healing
  • All of the chemical messenger proteins contained within platelets appear to exert bioregulatory actions, which affect soft tissue and cartilage repair, inflammation, bone healing, wound healing and blood loss
  • Upon contact with collagen fibres in exposed endothelium, usually when the wall to the blood vessel is damaged, the platelet is activated
  • This causes the platelet to change shape to increase its surface area, and at the same time the alpha granules start to release their growth factors (GF) that activate the body’s natural healing mechanism
  • Each growth factor has an important  role in the regeneration process. The main GF’s include:
    • platelet-derived growth factor (PDGFaa, PDGFbb, PDGFab)
    • transforming growth factor beta (TGF-b, TGF-b2)
    • vascular endothelial growth factor (VEGF)
    • insulin-like growth factor (IGF)
    • fibroblast growth factor (FGF)
    • epidermal growth factor (EGF).
  • All of these factors set the stage for tissue healing which involves intricate overlapping processes that are often categorized into haemostasis, inflammation, proliferation, and remodelling.

The benefits of PRP are thought to rely on the complementary and complex interactions between the concentrated growth factors and adhesive protein factors such as fibronectin and vitronectin, creating the regenerative process of chemotaxis, cell proliferation, removal of tissue debris, angiogenesis, extracellular matrix formation, osteoid production, and collagen synthesis.

Healing Cascade

Progression of platelet change upon activation

Biology of Platelet’s role in the Healing Cascade

Although the platelet is central to the coagulation cascade, it is also essential to tissue healing. Tissue healing involves an intricate process that is often categorized into three overlapping phases: inflammation, proliferation, and remodeling.

 The inflammatory phase ( typically 2-3 days)

The first step of the inflammatory phase is clot formation and platelet activation which results in release of growth, bioactive, and hemostatic factors. Once tissue injury occurs, the damaged tissue’s collagen fibres are exposed to the circulating platelets. Upon contact with the collage fibres, platelets are activated which causes the discharge of granule contents. Platelets contain two unique types of granules.

  • Alpha-granules contain a variety of haemostatic proteins, as well as growth factors, cytokines, chemokines and other proteins such as adhesion proteins. Of primary interest for tissue regeneration are the seven growth factors and three adhesion molecules found in the alpha granule.  
  • Dense granules contain factors that promote platelet aggregation.

95% of the platelet contained growth factors are released within 10 minutes of platelet activation. The remainder of growth factors are released over several days. In vivo and in vitro research also suggest that PRP induces over-expression of additional endogenous growth factors beyond what is contained within the platelet concentrate. Neutrophils and macrophages arrive at the site within hours of injury and provide phagocytosis of tissue debris.

The proliferative phase (lasts 2-4 weeks)

Within a few days of injury, fibroblasts enter the site and begin the proliferative phase. This phase is characterised by angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction.

The remodelling phase (lasting several weeks to months)

Finally, spanning from several weeks to months after an injury, the remodeling phase involves collagen maturation and apoptosis of excess cell material. Type III collagen is replaced by Type I collagen. This phase can last up to 12 months.