Comparison of the Effect of Intra-Tendon Applications of Recombinant
Human Platelet-Derived Growth Factor-BB, Platelet-Rich Plasma,
Steroids in a Rat Achilles Tendon Collagenase Model
Luis A. Solchaga,1Alison Bendele,2Vivek Shah,3Leo B. Snel,1Hans K. Kestler,3Joshua S. Dines,4Christopher K. Hee3
1Research and Development, BioMimetic Therapeutics, LLC, Franklin, Tennessee,
BioMimetic Therapeutics, LLC, Franklin, Tennessee,4Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, New York
2Bolder BioPATH, Boulder, Colorado,
Received 28 May 2013; accepted 14 August 2013
Published online 9 September 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jor.22483
(rhPDGF-BB), platelet-rich plasma (PRP) and corticosteroids in a rat tendinopathy model. Seven days after collagenase induction of
tendinopathy, a 30-ml IT injection was administered. Treatments included: saline; 3mg rhPDGF-BB; 10mg rhPDGF-BB; PRP; and
300mg triamcinolone acetonide (TCA). Outcomes were assessed 7 and 21 days after treatment. All groups exhibited good to excellent
repair. Relative to saline, cell proliferation increased 65% in the 10mg rhPDGF-BB group and decreased 74% in the TCA group;
inflammation decreased 65% in the TCA group. At 7 days, maximum load-to-failure was increased in the 3mg rhPDGF-BB group
relative to saline, PRP, and TCA (p<0.025). On day 21, maximum load-to-rupture was increased in the 10mg rhPDGF-BB group
relative to saline, PRP, and TCA (p<0.035) and in the 3mg rhPDGF-BB group compared to saline and TCA (p<0.027). Stiffness in the
10mg rhPDGF-BB group was increased compared to saline, PRP, and TCA (p<0.038). Histology demonstrated similar repair in all
groups. PRP and TCA did not improve mechanical properties compared to saline. Injections of rhPDGF-BB increased maximum load-
to-failure (3 and 10mg) and stiffness (10mg) relative to controls and commonly used treatments. ? 2013 Orthopaedic Research Society.
Published by Wiley Periodicals, Inc. J Orthop Res 32:145–150, 2014.
This study compared the effect of intra-tendon (IT) delivery of recombinant human platelet-derived growth factor-BB
tendinopathy; platelet-derived growth factor-BB; platelet-rich plasma; corticosteroid; biomechanics
Tendinopathy is a painful condition that develops as
result of tendon degeneration1,2and can affect tendons
throughout the body (e.g., rotator cuff, Achilles).
Tendinopathy leads to collagen degeneration, disorga-
nization, increased mucoid ground substance, prolifer-
ation of capillaries and arterioles, loss of mechanical
properties, and concomitant pain. These degenerative
changes occur without macroscopic tearing of the
tendon and may result from a failed healing response
to sub-failure injuries.1–3
Current treatment options for tendinopathy includ-
ing, but not limited to, exercise-based physical thera-
inflammatory drugs, extracorporeal shock wave thera-
py and surgical interventions4–11have met varying
degrees of success. These therapies often treat the
symptoms associated with the condition, but do not
address the underlying cause resulting in persistence
of the degeneration. While not considered a gold-
standard treatment, corticosteroid injections are often
administered for chronic tendinopathies. However,
there are concerns about the long-term safety and
efficacy of this therapy8–10due to adverse changes
within the tendon.12
Growth factors have also been assessed to promote
tendon healing. Autologous growth factors in the form
of platelet-rich plasma (PRP) have been studied;
however variability in the preparation and composi-
tion of PRP makes it difficult to compare results across
studies.13Additionally, variable clinical outcomes fol-
lowing PRP treatment for tendinopathy have been
reported.14,15As an alternative to PRP, recombinant
human platelet-derived growth factor-BB (rhPDGF-
BB) is a readily available, off-the-shelf option that
provides a consistent, therapeutic dose. Utilizing a
variety of delivery methods, animal models of tendon
injury have shown that rhPDGF-BB accelerates ten-
don healing by improving matrix remodeling, in-
proliferation.16–22We have previously reported that
rhPDGF-BB is efficacious in a non-ruptured, degener-
ated, tendinopathy model.23In contrast to corticoste-
roids, rhPDGF-BB addresses chronic tendinopathies
by inducing proliferation and migration of progenitor
cells and tenocytes,17,24–26which stimulate structural
repair of the degenerated tendon.
As a consequence of the deficiencies in clinical
outcome offered by contemporary therapies, the objec-
tive of this study was to compare the effect of intra-
tendon (IT) delivery of rhPDGF-BB, PRP and cortico-
steroids in a rat Achilles tendinopathy model. We
hypothesized that IT delivery of rhPDGF-BB would
result in increased biomechanical strength and im-
proved histological appearance compared to PRP and
Conflict of interest: BioMimetic Therapeutics, Inc.: L.A. Solchaga
(employee, stock/options), A. Bendele (institutional funds to
perform aspects of the study), V. Shah (employee, stock/options),
L.B. Snel (employee, stock/options), H.K. Kestler (employee,
stock/options), J.S. Dines (Scientific Advisory Board, consultant),
and C.K. Hee (employee, stock/options).
Grant sponsor: BioMimetic Therapeutics.
Correspondence to: Luis A. Solchaga (T: þ1-615-236-4511; F: þ1-
615-236-4470; E-mail: email@example.com)
# 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
JOURNAL OF ORTHOPAEDIC RESEARCH JANUARY 2014
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Additional supporting information may be found in the
online version of this article at the publisher’s web-site.
SOLCHAGA ET AL.
JOURNAL OF ORTHOPAEDIC RESEARCH JANUARY 2014