Drs. Arun K. Garg, Gregori M. Kurtzman, Renato Rossi Jr., and Maria del Pilar Rios discuss the benefits of using patient-derived autogenous blood concentrates mixed with particulate graft material
Clinically, there are situations where osseous grafting needs to be performed. This can vary from socket preservation following extraction, repair of bone loss at the furcation, filling voids between the socket walls and implant when immediate implants are planned, and treatment of exposed implant threads to sinus augmentation. These are managed by use of osseous particles, which can be allografts, autografts, xenografts, or even synthetic materials.
The typical problem with particles is the potential for dispersement during the initial healing period. Although they may be rehydrated or wetted with various liquids such as saline, water, or anesthetic, these liquids do not hold the particles together and allow them to spread in the area during healing. This will lead to less volume of healed graft at the site desired and may compromise the intended results. Utilization of patient-derived autogenous blood concentrates mixed with the particulate graft material improves graft handling during placement as well as maintenance at the intended site, eliminating dispersion potential. Autologous blood concentrates are defined as the concentrated portion of the patient’s blood following centrifuging that contains growth factors, platelets, white blood cells (WBCs), and fibrin but does not contain the red blood cell (RBC) portion of the blood.
Benefits of using autogenous blood concentrates with osseous graft materials
In the 1980s, several reports identified the pivotal role oxygen plays in wound healing.1-5 These studies were the first to recognize that growth factors promote healing related to the macrophage response to oxygen gradients, which secreted those wound-healing growth factors. Platelet-derived wound-healing factor (PDWHF) was first introduced clinically6 and continued on to platelet-rich plasma (PRP) utilized for over 2 decades to initiate wound healing. Thrombin-released platelets produce angiogenesis and collagen synthesis with fibrin eliciting a cellular exudate, followed by angiogenesis. In the early 1990s, Marx and Garg began work on using patient-derived blood as a fibrin source for use with osseous grafts to improve product handling. This fibrin adhesive was first published in 1994.7
Platelets secrete growth factors (PDGF-AA, PDGF-BB, and PDGF-AB) that stimulate mesenchymal stem cells to replicate, osteoblasts to replicate and produce osteoid, endothelial cells to replicate secreting basal lamina for new blood vessels, and fibroblasts to replicate producing collagen. Additionally, transforming growth factors (TGFß1 and TGFß2) and bone morphogenic protein (BMP) are present that stimulate matrix production and guide cell differentiation into bone. Other factors present in the autologous blood concentrates include vascular endothelial growth factor (VEGF), which supports new blood vessel development, and epithelial growth factor (EGF), which stimulates migration of the surrounding soft tissue to cover the area and form a basement membrane.
Incorporation of autologous blood concentrates such as PRP into a particulate graft material provides growth factors to accelerate healing of the graft, stimulating the host cells adjacent to the graft to convert into native bone. More rapid closure of the soft tissue using the patient’s own factors as that stimulating mechanism can be expected. The additional benefit is a gelatinous mass, termed “gummy bone,” that has improved handling without the dispersion issues found with graft particles mixed with saline or even allowed to absorb blood at the site (Figure 1). Gummy bone has a flexible putty-like consistency that can be cut to desired dimensions prior to placement and utilized in a variety of clinical graft situations, which include the following:
- socket grafting (Figure 2)
- filling voids around immediate implant placement (Figure 3)
- lateral sinus augmentation (Figure 4)
- crestal sinus augmentation (Figure 5)
- lateral ridge expansion (Figure 6)
- dehiscence repair at implant placement (Figure 7)
- furcation repair (Figure 8)
- grafting fill of defects on the lateral aspect of the ridge (Figure 9)
Fabrication of “gummy bone”
At the initiation of the surgical treatment, blood is drawn from the patient into red-top tubes. The red-top tubes are glass walled and contain no anticoagulant. These are then immediately centrifuged at 3,200 rpm for 3 minutes (about 600 gf) to create separation of the layers of the patient’s blood (Figure 10). Once centrifuging is complete, distinct layers present in the tube (Figure 11). For the purposes of creating gummy bone, the yellow layer, the plasma that is high in fibrin and platelets, will be used.
The osseous graft particles that will be used are dispensed into a sterile dish (Figure 12). The plasma liquid is withdrawn from the tube with a syringe and needle (Figure 13) and then dispensed into the dish containing the osseous graft material (Figure 14). This hydrates the dry graft particles and is allowed to sit for 10-12 minutes to coalesce into a gelatinous mass (Figure 15). Following the coalescence period, the gummy bone is formed and is ready for use (Figure 16). This does not need to be immediately used during the surgery and can sit in the dish until graft placement in the treatment process is ready. The gummy bone can be used as a single mass (Figure 17) when placing in large voids such as sinus augmentation or cut with scissors into smaller pieces (Figure 18) that can be incrementally placed into the surgical site. These pieces will adhere to each other when they are placed into contact with each other or the surrounding tissues.
As discussed, one of the main challenges to osseous grafting is handling of the graft materials during both placement and the initial healing period. Particle dispersement is not uncommon with particulate materials as when wetted by non-hematological liquids; this limits site blood from infusing into the graft placed initially, allowing dispersement to occur. Placing the dry particles into the site to be grafted, allowing blood from the surrounding tissues to wet it, also limits holding the mass together. There may be limited bleeding from the bone’s surface and not penetrate throughout the graft placed from bleeding at the soft tissue.
Fibrin from the autogenous blood concentrate has more favorable characteristics acting as “tissue glue” to hold the particulate graft into a pliable mass. This pliable material handles better, allowing easier shaping for the defect being treated with potential to increase width when needed that can not be easily accomplished with particulate bone when autogenous blood concentrates are not added. The added benefit of the platelets and associated growth factors stimulate angiogenesis, thus using the patient’s own systemic factors to aid in graft coalescence, organization, and maturation. Those practitioners, who are utilizing particulate graft materials in their treatment modalities, should consider incorporating autogenous blood concentrates like PRP to improve graft handling, eliminate particle dispersement during healing, and stimulate regeneration via the growth factors that are now incorporated within the placed graft material.
- Knighton DR, Silver IA, Hunt TK. Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration. Surgery. 1981;90(2):262-270.
- Knighton DR, Hunt TK, Scheuenstuhl H, et al. Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science. 1983;221(4617):1283-1285.
- Marx RE, Johnson RP. Studies in the radiobiology of osteoradionecrosis and their clinical significance. Oral Surg Oral Med Oral Pathol. 1987;64(4):379-390.
- Hunt TK. The physiology of wound healing. Ann Emerg Med. 1988;17(12):1265-1273.
- Marx RE, Ehler WJ, Tayapongsak P, Pierce LW. Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surg. 1990;160(5):519-524.
- Knighton DR, Hunt TK, Thakral KK, Goodson WH 3rd. Role of platelets and fibrin in the healing sequence: an in vivo study of angiogenesis and collagen synthesis. Ann Surg. 1982;196(4):379-388.
- Tayapongsak P, O’Brien DA, Monteiro CB, Arceo-Diaz LY. Autologous fibrin adhesive in mandibular reconstruction with particulate cancellous bone and marrow. J Oral Maxillofac Surg. 1994;52(2):161-165; discussion 166.