Injury, Int. J. Care Injured 40 (2009) S3, S44–S49
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Platelet-rich plasma, rhOP-1®(rhBMP-7) and frozen rib allograft for the
reconstruction of bony mandibular defects in sheep. A pilot experimental study
Francisco Forriola,*, Umile Giuseppe Longob, Carlos Concejoc, Purificacion Ripaldac, Nicola Maffullid,
aResearch Unit FREMAP Hospital, Ctra Pozuelo 61, 28220 Majadahonda, Madrid, Spain
bDepartment of Orthopaedic and Trauma Surgery, Campus Biomedico University, Rome, Italy
cOrthopaedic Research Laboratory, University of Navarra Pamplona, Spain
dDepartment of Trauma and Orthopaedic Surgery, University Hospital of North Staffordshire, Stoke-on-Trent, UK
a r t i c l e i n f o
a b s t r a c t
A 6cm bony defect in the mandible of 15 sheep, 8 years old, was reconstructed using variously
allograft of frozen rib, rhOP-1 (rh BMP-7), platelet-rich plasma (PRP), and a combination
of frozen rib allograft and rhOP-1. The histological, histomorphometric, immunohistochemical
and radiographic features of reconstruction were analysed. The animals were euthanised at
2 months postoperatively. In the control and PRP groups, no bone formation was detected.
The sheep receiving rhOP-1 showed some and those receiving both rhOP-1 and allograft
showed most new bone formation; in both groups this was through endochondral and also
fibrous ossification. The combination of bone allograft with growth factors demonstrated
osteoconductive as well as osteoinductive properties, and is appealing in the management of
© 2009 Elsevier Ltd. All rights reserved.
One of the challenges of orthopaedic surgery involves the
stimulation of bone healing, mostly using bone grafts. Tissue
engineering shows potential in the repair of bony defects by
supplying cells, growth factors and bone substitutes, alone or
in combination, to achieve bone healing.27Bone morphogenetic
proteins (BMPs) induce the differentiation of mature mesenchymal
stem cells into bone- and cartilage-forming cells.24,27As such,
these cells induce both direct (intramembranous) and endochondral
(through a cartilaginous intermediary stage) bone formation. The
end result is woven bone which remodels and becomes populated
with haematopoietic bone marrow.27
Growth factors, such as platelet-derived growth factor (PDGF)
and transforming growth factor beta (TGF-b), are osteo-promotive
and able to cause cells to divide but not to differentiate. They
produce expansion of the numbers of cells, and may cause cells
to augment production of cellular products such as extracellular
matrix proteins. Platelet rich plasma (PRP) is a major source of
PDGF and TGF b and may be used to enhance bone graft.14The
rationale for the local application of PRP in bone surgery is based
on the autologous release of growth factors present in the platelets,
without the risks of disease transmission or immunogenic reaction.
The effects of PRP on the enhancement of bone regeneration remain
debated however, and contradictory results have been obtained in
experimental investigations. According to some conclusions PRP
*Corresponding author. Tel.: +34916265811.
E-mail address: email@example.com (F. Forriol).
does seem to promote bone regeneration,7–9,11,22,25but according to
others this is still controversial.4,10,12,16
We therefore undertook a pilot study to compare the effects of
PRP, rhBMP-7 (rhOP-1®; Stryker Biotech, Hopkinton, MA), frozen rib
allograft, and the simultaneous implant of frozen rib allograft and
rhOP-1 in restoring bone defects in the mandibles of sheep.
Materials and methods
This study had the approval of the Committee for Animal
Experimentation of our university, and followed the current
regulations which are in accord with international law on
experimentation with animals.
The study involved 15 sheep (Ovis aries), all 8 years of age and
weighing 50–60kg. Each sheep was randomly assigned to one of
five experimental groups of three animals each, to receive one
of five allocated treatments. A random-numbers table allocated
the subjects; starting at an arbitrary point in the table, we
selected 15 sequential random numbers. The first three numbers
were assigned to first group, and the next assigned sequentially.
These assignments were then arranged in ascending order. This
procedure produced a random sequence of consecutive treatment
allocations. Sealed, opaque, numbered envelopes containing the
treatment assignments were prepared, with care that the order of
the envelopes exactly matched the allocation schedule.
0020-1383/ $ – see front matter © 2009 Elsevier Ltd. All rights reserved.
F. Forriol et al./Injury, Int. J. Care Injured 40 (2009) S44–S49S49
of the defects among the controls. The study demonstrated that
rhBMP-2 in a biodegradable carrier induced new bone formation.
Wang et al.26obtained good results in 5cm mandibular defects in
minipigs, using rhOP-1 included in carboxyl methylcellulose.
In conclusion, when comparing PRP, allograft of frozen rib, OP-1,
and combinations of frozen rib allograft and OP-1 to fill a bone
defect in the mandible of sheep, the simultaneous application
of frozen rib graft and OP-1 showed superior histological,
histomorphometric, immunohistochemical and radiographic bone
formation. The group receiving PRP alone in this way was not able to
produce any evidence of new bone formation. Further investigations
are required to better evaluate the roles of PRP, OP-1 and bone
graft in the management of bone defects, to clarify any potential
synergistic or additive effects and to bring new insights to the study
of bone regenerative medicine.
This work was supported by a grant from the Mapfre Foundation.
The OP-1®(Osigraft®) was kindly donated by Stryker Biotech,
Competing interests: The authors have no conflicts of interest to
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