The Journal of Bone and Joint Surgery (American). 2007;89:139-147.
doi:10.2106/JBJS.F.00388
© 2007 The Journal of Bone and Joint Surgery, Inc.
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Platelet-Rich Plasma Inhibits Demineralized Bone Matrix-Induced Bone Formation in Nude Mice

Don M. Ranly, DDS, PhD1, Christoph H. Lohmann, MD, MS2, Domenico Andreacchio, MD3, Barbara D. Boyan, PhD1 and Zvi Schwartz, DMD, PhD1

1 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive N.W., Atlanta, GA 30332-0363. E-mail address for B.D. Boyan: barbara.boyan{at}bme.gatech.edu
2 Department of Orthopaedics, University of Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany
3 Department of Orthopaedics, Fritz-Konig-Stift Bad Harzburg, Ilsenburger Straße 95, 38667 Bad Harzburg, Germany

Investigation performed at the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia

Disclosure: In support of their research for or preparation of this manuscript, one or more of the authors received grants or outside funding from DePuy Germany, the National Science Foundation, the Price Gilbert, Jr. Foundation, the Georgia Research Alliance, and the Georgia Tech/Emory Center for the Engineering of Living Tissues. In addition, one or more of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity (DePuy Germany). Also, commercial entities (Elsbeth-Bonhoff Foundation and Plus Orthopaedics) paid or directed, or agreed to pay or direct, benefits to a research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: It is unclear whether platelet-rich plasma is a clinically effective adjunct to osteoinductive agents such as demineralized bone matrix. It contains platelet-derived growth factor (PDGF), which decreases osteoinduction by human demineralized bone matrix in nude-mouse muscle, suggesting that platelet-rich plasma may also have a negative impact. This study tested the hypothesis that platelet-rich plasma reduces demineralized bone matrix-induced bone formation and that this effect varies with donor-dependent differences in platelet-rich plasma and demineralized bone matrix.

Methods: Human platelet-rich plasma was prepared from blood from six men (average age [and standard error of the mean], 29.2 ± 2.4 years). Platelet numbers were determined, and growth factors were quantified before and after platelet activation. Human demineralized bone matrix from two donors (demineralized bone matrix-1 and demineralized bone matrix-2) was mixed with activated platelet-rich plasma and was implanted bilaterally in the gastrocnemius muscle in eighty male nude mice (eight implants per variable). Fifty-six days after implantation, the hindlimb calf muscles were harvested for histological analysis. Osteoinduction was evaluated with use of a qualitative score and morphometric measurements of ossicle size, new bone formation, and residual demineralized bone matrix.

Results: Compared with platelet-poor plasma, platelet-rich plasma preparations exhibited a fourfold increase in the platelet count, a fifteenfold increase in the amount of transforming growth factor-beta, a sixfold increase in the amount of PDGF-BB, a fivefold increase in the amount of PDGF-AA, and a twofold increase in the amount of PDGF-AB. Demineralized bone matrix-1 was more osteoinductive than demineralized bone matrix-2, as determined on the basis of a greater ossicle area. The effect of platelet-rich plasma was either neutral or inhibitory depending on the demineralized bone matrix batch. When used with demineralized bone matrix-1, platelet-rich plasma did not alter the qualitative score or overall ossicle size, but it decreased the new bone area. When used with demineralized bone matrix-2, platelet-rich plasma reduced the qualitative score, ossicle area, and new bone area and increased the amount of residual demineralized bone matrix. The effects on osteoinduction also varied with the donor of the platelet-rich plasma.

Conclusions: Platelet-rich plasma decreased the osteoinductivity of demineralized bone matrix implanted in immunocom-promised mice, and the activities of both demineralized bone matrix and platelet-rich plasma were donor-dependent.

Clinical Relevance: Platelet-rich plasma may not be an appropriate adjunct to demineralized bone matrix in some clinical applications.


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