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Autologous Blood Concentrates: The Science of Natural Wound Healing
In many ways, traditional surgery and the medical arts have always tried to remove barriers to natural wound healing. Removal of these barriers proved that through replicable conditions and cases, standardized protocols could be created and followed to enhance wound healing. Over time, replication of results led to even more standardized techniques and procedures. For example, wound debridement and administering antibiotics demonstrably helped prevent infection, and stabilizing wounds and placing tissues in closer physical proximity promoted healing. These particular kinds of standardized, replicable surgical techniques can be labeled assistive or nonobstructive.1 However, beginning in the last quarter of the 20th century, a truly āproactiveā phase in surgical medicine began with the discovery that macrophages, reacting with oxygen, release growth factors that promote wound healing.2ā6 An assortment of cellular/tissue and oxygen-related therapies followed,7ā16 culminating only about two decades ago in the use of growth factors produced from concentrated autologous blood platelets to promote wound healing.17ā22 The result is medical scienceās present focus on platelet and other biologic/regenerative therapies as critical means for promoting, initiating, and sustaining wound healing.23
In the mid-1980s, platelets were understood essentially as cells that helped to stop bleeding. Over the next 20 years, the discovery of the various growth factors released by platelets gave birth to regenerative medical therapies, most of which are still in their infancy.24ā35 How the growth factors and functional matrix delivered by autologous blood concentrates induce wound healing is widely understood. The focus of current research is replicating and standardizing the preparation and administration of the autologous-derived product to best suit the donor-patient. Though a variety of preparation techniques, products, and nomenclatures have been tried, the good news is that no significant difference in the osteogenesis of growth factors has been evidenced.36ā40
Nevertheless, firmly establishing the science of platelet-rich plasma and other platelet-derived products requires an investigation of platelet biology, the release of growth factors, and the practical application for soft tissue healing and bone tissue regeneration. So far, the scientific journey of autologous blood concentrates has been remarkably expansive. The future of this journey promises to be more focused, even single-minded, toward its scientific destinationāeven more standardized products and procedures based on replicable results.
Platelet Biology
The first autologous blood concentrate was introduced in the literature as autologous fibrin adhesive and later changed to platelet-rich plasma (PRP). That term became standard, first in the oral surgery literature and then in all medical and dental surgical specialties. While many other terms have been used to describe autologous blood concentratesāparticularly in niche markets as a way to sell specific centrifuges and/or test tubesāPRP will be used throughout this book.
As an actor in the performance of regenerative medicine,41ā47 PRP provides two of the three essential components for allowing a wound to heal in place: growth factors and a scaffolding stage (Fig 1-1). The third ingredient for in situ tissue regeneration is the cells. PRP is a patientās own blood concentrate, modified in a relatively quick, efficient, safe, and simple procedure, to obtain a dense concentration of platelets. The autologous nature of PRP precludes disease transmission to the patient or other adverse reactions. To provide wound healing benefit to the patient, PRP generally must have at least four to seven times the normal concentration of platelets, or roughly 1 million platelets per microliter.48 A blood clot in a wound consists mostly of red blood cells and much smaller percentages of platelets and white blood cells (Fig 1-2). Applying PRP to such a wound essentially replaces red blood cells with growth factorāproducing platelets and a fibrin network, thus (at least in theory) greatly enhancing the healing of wounds and migration of cells, as well as the regeneration of bone and soft tissue.
FIG 1-1 Components of blood that are concentrated in PRP.
When bone marrow megakaryocytes undergo cytoplasmic fragmentation, the anuclear platelet cells enter the circulatory system. The relatively tiny platelet is about one-fourth the size of a red blood cell (approximately 8 Āµm in diameter) and six to seven times smaller than a lymphocyte; however, the plateletās membrane extends pseudopodially via invaginations, which provide an expansive, dynamic, and vigorous surface area for the cell membrane during activation.1,49 The plasticity and resilience of the plateletās pseudopodic membrane enable its vascular-sealing qualities, along with its ability to form a thrombus and fibrin clot, as well as clot retraction when its hemostatic labors are complete50 (Fig 1-3). Generally, the larger and younger the platelet, the greater its hemostatic qualities and the greater the quantities of growth factors contained within it.23,51,52
The short lives of platelets (240 hours or less) are very actively spent synthesizing and secreting growth factors as part of the blood-clotting process. The platelet contains lysosomes, ribosomes, mitochondria, and an assortment of intercellular proteins that help form its shape as well as its mobility. The platelet cell also contains storage organelles that consist of lysosomal granules (for storing enzymes for digestion), dense granules (for storing and secreting adenosine diphosphate [ADP]), and alpha granules (for summoning and activating other platelets via nascent growth factors) (Fig 1-4).53ā55
The growth factors stored in the alpha granules include platelet-derived growth factor (PDGF) isomers labeled AA, BB, and AB (referred to as polypeptide ādimersā because of their two active sites, which are actually antiparallel monomers); transforming growth factor (TGF) isomers beta 1 and 2; vascular endothelial growth factor (VEGF); and epithelial growth factor (EGF). Growth factors not contained in platelets include insulinlike growth factors (IGF) 1 and 2 and bone morphogenetic protein (BMP). The blood-clotting process activates the alpha granules in platelets to secrete growth factors, both when the platelets circulate normally in the blood and when the platelets are concentrated in PRP. Alpha granules move toward the membrane and bind themselves to its surface, causing histone and carbohydrate side chains to combine with, and ...