The Journal of Bone and Joint Surgery (American). 2009;91:1459-1470.
doi:10.2106/JBJS.H.00246
© 2009 The Journal of Bone and Joint Surgery, Inc.
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The Effect of Thrombin Activation of Platelet-Rich Plasma on Demineralized Bone Matrix Osteoinductivity

Bo Han, PhD1, Jennifer Woodell-May, PhD2, Michael Ponticiello, MS3, Zhi Yang, MD1 and Marcel Nimni, PhD1

1 Department of Surgery, University of Southern California, 1840 North Soto Street EDM-191, Los Angeles, CA 90032. E-mail address for B. Han: bohan{at}usc.edu
2 Biomet, Incorporated, 56 East Bell Drive, Warsaw, IN 46581
3 Interpore Cross International, 181 Technology Drive, Irvine, CA 92618

Investigation performed at Keck School of Medicine, University of Southern California, Los Angeles, California

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from Biomet (Warsaw, Indiana) and the Wright Foundation (University of Southern California, Los Angeles, California). In addition, one or more of the authors or a member of his or her immediate family received, in any one year, payments or other benefits in excess of $10,000 or a commitment or agreement to provide such benefits from a commercial entity (Biomet). No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

Background: Demineralized bone matrix is an osteoinductive and osteoconductive material that is often used in orthopaedic surgery to induce bone formation. Autologous platelet-rich plasma, which contains proliferative and chemoattractant growth factors, has been used as a demineralized bone matrix adjuvant with mixed results. One variable during clinical use appears to be whether the platelet-rich plasma is activated with thrombin or is implanted in a liquid form with intact platelets. The objective of the present study was to determine if platelet-rich plasma can increase the osteoinductivity of demineralized bone matrix when used without thrombin activation.

Methods: The bioactivity of the demineralized bone matrix was evaluated in vitro by determining alkaline phosphatase production by C2C12 myoblast cells. The effect of thrombin activation on platelet-rich plasma was studied in vitro by evaluating osteosarcoma and bone marrow stromal cells for cell number and transforming growth factor-β1 activation. Demineralized bone matrices supplemented with platelet-rich plasma, with or without thrombin activation, were implanted intramuscularly in athymic rats and were examined at fourteen, twenty-eight, and fifty-six days. Histological samples were analyzed for osteogenesis and chondrogenesis. Osteogenesis was further characterized on the basis of alkaline phosphatase activity.

Results: In vitro, thrombin triggered an immediate release of growth factors from the platelet-rich plasma, and the platelet-rich plasma increased the number of both osteosarcoma and stromal cells in a dose-dependent manner. Thrombin activation of the platelet-rich plasma eliminated such stimulatory effects. In vivo, the platelet-rich plasma stimulated chondrogenesis on Day 14 and osteogenesis on Days 28 and 56, whereas thrombin-activated platelet-rich plasma acted as an inhibitor of such events. In addition, inflammatory cells were detected in demineralized bone matrix samples that were mixed with thrombin-activated platelet-rich plasma. These cells were not present in matrix mixed with platelet-rich plasma alone.

Conclusions: Platelet-rich plasma significantly increased in vivo demineralized bone matrix osteoinductivity only when used without thrombin activation.

Clinical Relevance: Platelet-rich plasma has the potential to increase the osteoinductivity of demineralized bone matrix in clinical applications. On the other hand, its activation by thrombin immediately prior to implantation significantly inhibits this activity.


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