Platelet-Rich Plasma for Bone Graft Enhancement in Sinus Floor Augmentation With Simultaneous Implant Placement: Patient Series Study

Platelet-Rich Plasma for Bone Graft Enhancement in Sinus Floor Augmentation With Simultaneous Implant Placement: Patient Series Study
March 2004
Mazor, Ziv DMD*; Peleg, Michael DMDÇƒÜ; Garg, Arun K. DMDÇƒ?; Luboshitz, Jacob MD¨?
Implant Dentistry: Volume 13(1) March 2004 pp 65-72
Lippincott Williams & Wilkins
*Private practice of Periodontology, Ra'anana, Israel.
ÇƒÜAssistant Professor of Surgery, Division of Oral & Maxillofacial Surgery, University of Miami School of Medicine, Miami, Florida.
Çƒ?Professor of Surgery, Division of Oral & Maxillofacial Surgery, University of Miami School of Medicine, Miami, Florida.
¨?Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Israel.
Reprint requests and correspondence to:
Arun K. Garg, DMD
6633 Roxbury Lane
Miami Beach, FL 33141
Phone: (305) 331-6481
Fax: (305) 865-1148
E-mail: arungarg@pol.net
Abstract
The use of autologous platelet-rich plasma (PRP) as a source for growth factors in bone grafting is a relatively new and promising technique. Early controlled studies indicate that combining PRP with autologous bone grafts significantly enhances the rate of bone formation and maturation. The study consisted of 105 patients who required sinus augmentation with crestal bone height of less than 5 mm in the posterior maxilla. All patients received a composite bone graft that consisted of 30% to 40% autogenous bone harvested from the lateral wall of the maxilla zygomatic-maxillary buttress and the tuberosity and 60% to 70% xenograft. A total of 50 mL of blood was obtained from each patient before the surgical treatment for preparation of 10 mL of PRP. The graft-PRP mixture was activated by human thrombin. All sinus augmentations were carried out simultaneously with dental implants. At 6 months postoperatively, implants were exposed showing no clinical evidence of crestal bone loss around the implants both clinically and radiographically. All implants were clinically osseointegrated and loaded with fixed porcelain fused to metal prosthesis. The use of PRP in augmenting the severely atrophic posterior maxilla has obvious clinical benefits in terms of reducing the healing period of bone maturation, better graft handling, and accelerated soft tissue healing.
For more than a decade, bone augmentation for supporting osseointegrated dental implants has become a routinely used technique in dentistry. Current research aims toward improving the ability to manage bone grafts. Guided bone regeneration is one beneficial outcome of this research. Recently, the focus has been on the possibility of applying growth factors to enhance bone regeneration. These growth factors regulate key cellular events such as chemotaxis, mitogenesis, and differentiation, which are all important steps in the process of osteogenesis and bone regeneration. These growth factors applied to bone graft material could accelerate the bone-regenerative process. One strategy for harnessing this benefit is to apply autologous platelet-rich plasma (PRP, Harvest Technologies, Plymouth, MA) to bone graft sites. 1
Platelet alpha granules contain several growth factors, including platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-?¸), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF), which are absent in normal plasma. 2 Other important platelet proteins include platelet-derived endothelial growth factor 3 and factor XIII, which accounts for 50% of the total blood factor XIII. 4
PDGF is considered a principle growth factor, which appears on the wound surface, initiating connective tissue healing, bone regeneration, and repair. A brief rather than prolonged exposure to PDGF enhances bone formation in vivo. 5 TGF-?¸ is involved in general connective tissue repair and bone regeneration. Its most important roles appear to be chemotaxis of osteoblast precursors and control of a steady-state level of osteoblast differentiation in vivo. 6 TGF-?¸ also increases cell proliferation of mesenchymal stem cells (MSC) in vitro and induces bone formation by MSC in vivo. 7 The combined effect of growth factors results in synergistic stimulation of different metabolic function as shown by the strong increase in proliferation and chemotaxis of osteoblasts in response to PDGF-BB and TGF-?¸1. 8
Bone regeneration is dependent on blood supply to newly formed tissue, and blood supply is dependent on the rate of new blood vessel formation, ie, angiogenesis, a coordinated sequence of events controlled by growth factors such as VEGF induction of endothelial cell assembly, PDGF-BB recruitment of pericytes and smooth muscle cells, and TGF-?¸1 and angiopoietin-1 stabilization of the nascent vessel. 9,10
The anatomic site and the carrier medium by which they are applied determine the local concentration of these growth factors. The half-life of recombinant PDGF-BB (rPDGF-BB) and recombinant TGF-?¸1 (rTGF-?¸1) applied in aqueous buffer is approximately 1 hour in a dermal wound bed, with only negligible activity retained after 24 hours. 11 In contrast, the half-life of rPDGF-BB applied in methylcellulose gel to beagle dog premolar teeth roots is 4.2 hours, with greater than 96% of its original activity eliminated by 96 hours. 12 Although these growth factors have a relatively short pharmacologic half-life, their biologic effect on tissue repair could last up to 21 days. 11
Thrombin, the most potent physiological activator of platelets, induces an effect on platelets at a low nanomolar concentration. Secretion of the alpha granules content could be evident as early as 5 to 10 seconds after addition of thrombin and is complete within 60 to 90 seconds. 13
Thrombin has an additional role as a cellular mitogen. It stimulates growth-clustering and collagen lattice contraction of human gingival fibroblasts 14 and proliferation of human osteoblasts through the protease-activated receptor (PAR). 15 Thrombin partially promotes angiogenesis by potentiation of VEGF-mediated angiogenesis. 16 The combination of thrombin and growth factors often demonstrates a synergistic effect on cellular proliferation. 17 In addition to its role as a potent activator of platelet secretion and a potent mitogen, thrombin plays a major role in producing a stable scaffold for bone particles. It cleaves the Aa and Bb chains of fibrinogen to enable formation of fibrin monomers sequentially binding to each other to form stable fibrin strands. Thrombin also activates factor XIII that crosslinks the covalently bounded adjacent fibrin strands to yield a stable fibrin clot that cannot be easily disrupted. 18 The stability, resistance to fibrinolysis, and permeability of fibrin clot are dependent on the level of thrombin generated at the beginning of the process. 19 Platelet activation by thrombin leads to platelet aggregation by transforming their integrin receptor to its active form in which it binds its ligand: fibrinogen. 20 All of these integrated activities of thrombin produce a stable platelet-fibrin clot that serves as a scaffold to bind and hold the bone graft particles together in a structure called bone-coagulum (Fig. 1). It is important to understand that all of these growth factors exert their effect by binding to specific receptors at the cell membrane.
In an animal model, Anitua 21 has shown that plasma-rich growth factors have a beneficial effect by enhancing and accelerating bone regeneration and soft tissue healing. In a pioneer study, Marx et al. 1 demonstrated that mandibular bone grafts containing PRP were consistently rated as having reached bone maturity levels nearly twice of that compared with the control. Additionally, histomorphometry assessment revealed higher bone density in the PRP-treated group.
This study reports our experience with the use of PRP for bone graft enhancement in patients who underwent a sinus augmentation procedure.
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