PRP acts by degranulation of alpha granules from platelets, which contain several growth factors. Active secretion of these growth factors is initiated by the blood coagulation process and begins within 10 minutes of coagulation. More than 95% of pre-synthesized growth factors are secreted within 1 hour. Therefore, PRP must be prepared in an anticoagulant state and should be used in grafts, flaps, or wounds within 10 minutes of clot onset. Studies that do not use anticoagulated whole blood are not true PRP studies and are misleading.
As platelets are activated by the clotting process, growth factors are secreted from the cell through the cell membrane. In this process, alpha particles fuse to platelet cell membranes, and protein growth factors complete the bioactive state by adding histone and carbohydrate side chains to these proteins. Thus, platelets damaged or inactivated by PRP treatment do not secrete bioactive growth factors and may lead to disappointing results. Secreted growth factors bind immediately to the outer surface of the membrane of cells in the graft, flap, or wound via transmembrane receptors.
Studies have shown that adult human mesenchymal stem cells, osteoblasts, fibroblasts, endothelial cells, and epidermal cells express cell membrane receptors for growth factors in PRP. These transmembrane receptors in turn induce the activation of endogenous internal signaling proteins that lead to the expression (unlocking) of normal cellular gene sequences, such as cell proliferation, matrix formation, osteoid formation, collagen synthesis, etc.
The importance of this knowledge is that PRP growth factors never enter the cell or its nucleus, they are not mutagenic, they simply accelerate stimulation of normal healing. Therefore, PRP has no ability to induce tumor formation.
After the initial burst of PRP-associated growth factors, platelets synthesize and secrete additional growth factors for the remaining 7 days of their life span. Once platelets are depleted and dead, macrophages that reach the region through platelet-stimulated blood vessels grow inward to take on the role of wound healing regulator by secreting some of the same growth factors as well as others. Thus, the number of platelets in the graft, wound, or blood clot attached to the flap determines how quickly the wound heals. PRP just adds to that number.
How many platelets is enough?
Studies have shown that the proliferation and differentiation of adult MSCS are directly related to platelet concentration. They showed dose-response curves, which indicated that an adequate cellular response to platelet concentration first began when four to five times the baseline platelet count was reached. A similar study showed that increasing platelet concentration also enhanced fibroblast proliferation and type I collagen production, and that most of the response was PH-dependent, with the best response occurring at more acidic pH levels.
These studies not only demonstrate the need for devices to concentrate sufficient platelets, but also explain the enhanced bone regeneration outcomes and enhanced soft tissue outcomes associated with PRP.
Since most people have a baseline platelet count of 200,000±75,000 per μl, a PRP platelet count of 1 million per μl measured in a standard 6-ml aliquots has become the benchmark for “therapeutic PRP.” Importantly, studies have shown that this platelet concentration is achieved when treatment levels are reached, thereby releasing growth factors.
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Post time: Sep-01-2022