Platelet Rich Plasma & Platelet Rich Plasma Gel: Engineering
the Biocellular Medicine for Improved Clinical Efficiency
Normal healthy bone has the ability to spontaneously regenerate during remodeling or after minor injury. However, if the defect site exceeds a critical size (such that the bone will not spontaneously heal during the animal’s or patient’s lifetime), bone grafting is required to regenerate new tissue. Common bone graft biomaterials include autografts (a patient’s own bone), allografts (human cadaver bone), xenografts (animal bone), and synthetic biomaterials (scaffolds). Of these, autografts are used as the current standard since they are osteogenic, osteoconductive, and osteoinductive. Although autografts produce satisfactory results, they carry the risk of donor site morbidity and are limited in availability. With auto-, allo-, and xenografts, each having their own unique set of disadvantages, synthetic biomaterials are emerging as potentially viable substitutes for bone regeneration, considering that they satisfy requirements such as being biocompatible, biodegradable, and bioactive. Platelet-rich plasma (PRP, a platelet concentrate) can be used alone or in combination with scaffolds and biomolecules as an alternative bone graft substitute.
PRP is a concentration of platelets in blood plasma. In a healthy human, average circulating platelet counts are approximately 200,000 platelets/μL. Clinically, PRP is typically administered at a several folds increase over that baseline concentration. The interest in concentrated platelets is derived from their early role in the normal healing response. Platelets contain more than 300 biologically active molecules which are released upon activation and subsequently influence the tissue regeneration process. Activated platelet-derived factors serve as messengers and regulators that influence a variety of cell-cell and cell-extracellular matrix (ECM) interactions. In addition, it has been shown that a linear relationship exists between platelet concentrations and the concentration of available cytokines. This is attractive to tissue engineering and regenerative medicine since increasing the number of platelets available in a defect/injury site will increase the amount of bioactive cytokines capable of stimulating and accelerating the repair process.
Platelet alpha and dense granules release an array of bioactive molecules upon activation. Activated PRP contains platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and others. PRP also contains a number of macrophage and monocyte mediators and a variety of interleukins (IL) capable of mediating inflammation. Furthermore, the plasma component of PRP contains the proteins fibrinogen, albumin, several immunoglobulins, and more. Several of these bioactive molecules play a significant role in bone remodeling.
The clinical use of PRP has expanded into treatment of multiple tissues, albeit with varying degrees of effectiveness. PRP therapy (in various delivery methods) has been implemented to stimulate tissue regeneration in bone, cartilage, skin, ligament, tendon, muscle, and more. This therapy typically involves an autologous blood draw and centrifugation to separate and obtain the platelet concentrate. PRP is then activated (commonly by CaCl2 and/or thrombin) and applied to the defect/injury site. However, it has been shown that thrombin as a clotting agent to form a platelet gel can result in rapid activation of platelets and ultimately a mass release of growth factors (70% released within 10 minutes and nearly 100% released within 1 hour). These growth factors, which undergo a burst release, are cleared before they can have any stimulatory effects on cells. When platelet gels are formed using CaCl2, growth factor release can be slowed.
As bone regeneration is a lengthy process (adequate strength typically restored within 3–6 months), there is an obvious need for effective delivery vehicles capable of the sustained release of PRP-derived factors over an extended period of time to maximize their regenerative potential.