Platelet-Rich Plasma in Orthopaedic Surgery_A Critical Analysis Review (1)

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Platelet-Rich Plasma in
Orthopaedic Surgery

A Critical Analysis Review

Dean Wang, MD Abstract
Scott A. Rodeo, MD » Platelet-rich plasma has shown great promise and potential to
Investigation performed at the Sports stimulate biologic activity in difficult-to-heal musculoskeletal tissue.
Medicine and Shoulder Service, However, the optimal formulation, method of administration, and
Hospital for Special Surgery, dosing for different tissues have yet to be determined.
New York, NY
» Within a given platelet-rich plasma preparation technique, there
COPYRIGHT © 2017 BY THE is a high degree of inter-subject and intra-subject variability in the
JOURNAL OF BONE AND JOINT composition of platelet-rich plasma produced. This likely contributes to
SURGERY, INCORPORATED the inconsistent results reported in the current platelet-rich plasma
literature.

» Current evidence best supports the use of platelet-rich plasma as
a treatment for osteoarthritis of the knee. Evidence on the use of
platelet-rich plasma as a treatment or adjunct for rotator cuff repair,
lateral epicondylitis, hamstring injuries, anterior cruciate ligament
(ACL) reconstruction, patellar tendinopathy, Achilles tendinopathy, and
fractures is inconsistent or only available from low-powered studies. To
our knowledge, no comparative studies examining platelet-rich plasma
treatment for partial ulnar collateral ligament tears in the elbow
currently exist.

» Current evidence suggests that different platelet-rich plasma formu-
lations are needed for different tissues and pathologies. Ultimately,
improved understanding of the underlying structural and compositional
deficiencies of the injured tissue will help to identify the biologic needs
that can potentially be targeted with platelet-rich plasma.

P latelet-rich plasma, an autolo- transforming growth factor-beta, are all
gous blood concentrate, has thought to facilitate and enhance the
gained popularity among phy- healing of injured tissue. As a result,
sicians as a treatment modality platelet-rich plasma is believed to augment
for orthopaedic injuries. The biologic the natural healing process by increasing
rationale for its use involves the local the concentration of these cytokines at the
delivery of growth factors, inflammation site of injury. The autologous nature and
modulators, and cell adhesion molecules thus the safety of platelet-rich plasma
that are released from a concentrated pool make it an attractive treatment option.
of degranulating platelets. These bioactive Categorized as a minimally manipulated
proteins, which include platelet-derived tissue and autologous blood product,
growth factor, insulin-like growth factors platelet-rich plasma has avoided the regu-
I and II, fibroblast growth factor, latory hurdles of extensive preclinical and
vascular endothelial growth factor, and clinical trial testing, resulting in its

Disclosure: No external funds were received in support of this study. The Disclosure of Potential
Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/
JBJSREV/A260).

·JBJS REVIEWS 2017;5(9):e7 http://dx.doi.org/10.2106/JBJS.RVW.17.00024 1

| Platelet-Rich Plasma in Orthopaedic Surgery

widespread use despite the lack of composition is useful for the compari- arthroscopic rotator cuff repair surgical
consistent evidence supporting its effi- son of studies. Mishra et al.7 proposed procedure. When compared with con-
cacy. This article provides a critical a system that classifies platelet-rich trol patients, patients who received
analysis of the available literature on plasma by leukocyte content, platelet platelet-rich plasma at the time of rotator
platelet-rich plasma treatment in or- number, and activation (Table I), cuff repair did not report improved
thopaedic surgery, with a focus on which will be used to describe the clinical outcome scores, including
recent Level-I and II studies. noncommercial platelet-rich plasma the Constant score14, University of
preparations in this review. California Los Angeles (UCLA) score14,
Platelet-Rich Plasma Preparation American Shoulder and Elbow Surgeons
Because the optimal platelet-rich Rotator Cuff Repair (ASES) score14, and Simple Shoulder
plasma composition for treating differ- Adjunctive use of platelet-rich plasma Test15, after a minimum 12-month
ent orthopaedic pathologies remains during arthroscopic rotator cuff repair follow-up. In a meta-analysis of 11 Level-I
unknown, there remains substantial has been extensively studied within the or II studies, Warth et al.8 showed a sig-
variability in the methods of platelet- platelet-rich plasma literature, with nificantly decreased improvement in the
rich plasma production among com- multiple randomized controlled trials Constant score when platelet-rich plasma
mercial systems1,2. Prior studies have (RCTs) and meta-analyses on the topic. was injected over the tendon surface
demonstrated differences in platelet, However, the heterogeneity of these compared with application at the tendon-
leukocyte, and growth factor content studies, with regard to platelet-rich bone interface (p 5 0.046); however, this
depending on separation technique3. plasma composition, means of admin- difference did not reach the minimal
To complicate matters further, within a istration, tear size, and repair technique clinically important difference.
given separation technique, there is a (single-row or double-row), makes it
high degree of inter-subject and intra- difficult to compare results. Despite the The effect of platelet-rich plasma
subject variability in the composition number of variables, the overwhelming on retear rates after arthroscopic rotator
of platelet-rich plasma produced4. This majority of studies have shown no dif- cuff repair is more controversial. Of
likely contributes to the inconsistency ference in clinical outcomes after rotator the studies that assessed the integrity of
of results reported in the literature. cuff repair in patients who received the cuff repair at least 6 months post-
Special attention has been devoted to platelet-rich plasma augmentation operatively, the majority demonstrated
the leukocyte concentration within compared with controls8-13. Saltzman no difference in retear rates8,11,12,16-20.
platelet-rich plasma, with leukocyte- et al.12 performed a systematic review of Nevertheless, some studies have shown
rich platelet-rich plasma associated 7 meta-analyses, each with a Quality of that, in certain settings, platelet-rich
with a higher concentration of Reporting Meta-analyses (QUORUM) plasma applied at the tendon-bone in-
pro-inflammatory mediators such as score of .15, evaluating platelet-rich terface decreased retear rates21-23. In the
interleukin-1 and tumor necrosis factor- plasma use at the time of the meta-analysis by Warth et al.8, retear
alpha5. As a result, some have suggested rates were significantly decreased when
that leukocyte-reduced platelet-rich
plasma is more suitable for intra- TABLE I Platelet-Rich Plasma Classification System by
articular treatment, although there is Mishra et al.7
currently no clinical evidence to sub-
stantiate this recommendation. Ulti- Type or Subtype Leukocytes Activated*
mately, more research is needed to
determine the optimal platelet-rich Type Increased No
plasma formulation (leukocyte and 1 Increased Yes
platelet number, other plasma pro- 2 Minimal or none No
teins), activation status (when and how 3 Minimal or none Yes
to initiate platelet degranulation), need 4
for a carrier vehicle (fibrin matrix or Platelets $5 times baseline†
collagen-based scaffold), and dosing Subtype Platelets ,5 times baseline
regimen (single injection compared A
with serial injection and intraoperative B
injection compared with delayed in-
jection)6. Because of the heterogeneity *Users can choose to activate platelets endogenously or through the addition of
of currently utilized platelet-rich
plasma formulations, a validated clas- an exogenous clotting factor (e.g., CaCl2) to any commercially available system.
sification system characterizing the †Buffy coat-based systems (leukocyte-rich) typically produce highly variable platelet
concentrations ranging from 3 to 8 times baseline (subtype A or B), whereas plasma-
based systems (leukocyte-poor) typically produce platelet concentrations ,5 times
baseline (subtype B).

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platelet-rich plasma was used for tears Comparative studies are needed to 6 months and 1 year27,29. Patients
.3 cm in anterior-posterior length us- evaluate whether platelet-rich plasma treated with platelet-rich plasma con-
ing a double-row repair technique (p 5 injections can actually stimulate the tinued to progressively improve, and
0.046). Additionally, retear rates were healing of partial UCL injuries. those treated with corticosteroid de-
decreased when platelet-rich fibrin ma- clined at 12 weeks. Overall, the avail-
trices were used to supplement repairs Lateral Epicondylitis able evidence suggests that platelet-rich
compared with liquid-based platelet- Several RCTs have compared platelet- plasma injections may provide some
rich plasma, although this result did not rich plasma injection with various con- benefit in the long term, but ultimately,
reach significance (p 5 0.054). Saltzman trols for the treatment of symptomatic more studies are needed to clearly de-
et al. performed a subgroup analysis lateral epicondylitis27-32. Most of the lineate the effects of platelet-rich
involving 4 meta-analyses and suggested studies used type-1A platelet-rich plasma from the natural course of ten-
that application of a platelet-rich fibrin plasma in their treatment (leukocyte- don healing and symptom resolution.
matrix at the bone-tendon interface rich, with platelet concentration .5
could potentially be an avenue for de- times the baseline). In a double-blind, Hamstring Injuries
creasing the retear rate in the setting multicenter study consisting of 230 pa- Platelet-rich plasma injection near the
of small and medium tears repaired tients, Mishra et al.31 compared tendon proximal myotendinous hamstring ori-
with a double-row technique12. How- needling with and without platelet-rich gin has been theorized to help to speed
ever, to our knowledge, no studies have plasma (Biomet GPS III). No significant the recovery process after acute ham-
thus far evaluated these variables in differences were found at 12 weeks, string injury. Several RCTs have exam-
combination. but the platelet-rich plasma group ined the treatment of grade-2 hamstring
reported superior improvement in pain injuries with platelet-rich plasma injec-
Elbow Ulnar Collateral Ligament with resisted wrist extension at 24 weeks. tion, with time to return to play as
(UCL) Injuries There were no differences in the the primary outcome measure35-37.
There is a paucity of data on the use of Patient-Rated Tennis Elbow Evalua- Hamilton et al.35 compared treatment
platelet-rich plasma for treating partial tion33 between groups. Rehabilitation with a single platelet-rich plasma injec-
ulnar collateral ligament (UCL) tears was not standardized across the trial tion (Biomet GPS III) with that with
of the elbow, with the current literature, centers, a weakness acknowledged by a platelet-poor plasma injection or no
to our knowledge, consisting of only the authors. In a single-blind study of injection control in a study of 90 pro-
2 case series24,25. Podesta et al.24 exam- 28 patients, Thanasas et al.34 compared fessional athletes. All participants un-
ined 34 overhead-throwing athletes with treatment with a single injection of derwent a standardized rehabilitation
partial UCL tears treated with a single platelet-rich plasma (Biomet GPS III) program. Although the platelet-rich
platelet-rich plasma injection (Arterio- with that of autologous blood. Both plasma group returned to play 5.7 days
cyte Magellan) and physical therapy. treatment groups underwent physical sooner than the platelet-poor plasma
At a mean follow-up of 70 weeks, the therapy. Pain reduction was superior group, there was no difference in the
authors reported a mean time to return in the platelet-rich plasma group com- time to return to play between the
to play of 12 weeks, significant im- pared with the autologous blood group platelet-rich plasma group and the con-
provements in Kerlan-Jobe Orthopae- at 6 weeks, but this difference dissi- trol group. Furthermore, there was no
dic Clinic26 and Disabilities of the Arm, pated at 12 and 24 weeks. In a double- significant difference in the reinjury
Shoulder and Hand (DASH)14 out- blind study of 50 patients, Montalvan rate 6 months after returning to com-
comes scores (p , 0.001), and decreased et al.32 performed 2 injections of petition among all treatment groups. In
dynamic medial elbow joint space wid- either platelet-rich plasma (Arthrex another double-blind study, Reurink
ening. One patient had treatment that ACP) or saline solution at an interval of et al.37 compared treatment with 2 in-
failed and underwent UCL reconstruc- 4 weeks. No differences in subjective jections of either platelet-rich plasma
tion at 31 weeks after injection. Dines pain scores and pain with isometric (Arthrex ACP) or saline solution in 80
et al.25 reviewed 44 baseball players with wrist extension were found between athletes. The first injection was given
partial UCL tears treated with platelet- groups at all time points within the final within 5 days of injury and the second
rich plasma injections (Arthrex ACP 12-month follow-up. Conversely, 2 injection was given 5 to 7 days later.
[Autologous Conditioned Plasma]) and RCTs on the same patient population There were no differences between
physical therapy. Sixteen patients had compared treatment with platelet-rich treatment groups with regard to time to
1 injection, 6 patients had 2 injections, plasma injections (Biomet GPS III) return to play, reinjury rate, subjective
and 22 patients had 3 injections. Simi- with treatment with corticosteroid in- scores, strength testing, and magnetic
larly, the mean time to return to play was jections and found superior reductions resonance imaging (MRI) measures. In
12 weeks. The major limitation of these in pain and improvements in DASH contrast, A Hamid et al.36 compared a
studies is the lack of a control group. scores with platelet-rich plasma at single platelet-rich plasma injection

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(Biomet GPS III) combined with a re- and clinical implications of these findings 3 patients subsequently crossed over into
habilitation program with rehabilitation are unclear. the platelet-rich plasma group. Out-
alone in a smaller study of 24 athletes. come measures included the Victorian
Return to play and pain severity or in- The effect of adjunctive platelet- Institute of Sports Assessment (VISA)51,
terference, which was assessed with the rich plasma applied to the graft-tunnel VAS, Tegner activity scale52, Lysholm
Brief Pain Injury-Short Form (BPI- interface has been evaluated, with most knee scale52, and 12-Item Short Form
SF)38, were examined. The platelet-rich studies indicating that it does not sig- Survey (SF-12). The platelet-rich
plasma group returned to play sooner nificantly affect tunnel healing or plasma group had greater improvement
(26.7 days) than controls (42.5 days), widening39,45-48. In a double-blind in VISA scores than the control group at
but there was no difference in pain scores study, Vogrin et al.46 compared ACL 12 weeks but not at $26 weeks. Con-
between groups. More research, perhaps reconstruction using hamstring graft versely, the control group had greater
with the use of leukocyte-rich platelet- with and without platelet-rich plasma improvement in Lysholm scores than
rich plasma that has shown promise in (Arteriocyte Magellan). Vascularization the platelet-rich plasma group at $26
the treatment of lateral epicondylitis, is was assessed by MRI. Although no dif- weeks. There were no differences be-
required. ferences between groups was seen in the tween groups in any other outcome
intra-articular portion of the ACL grafts, measure. In another RCT of 46 patients,
Anterior Cruciate Ligament increased vascularization was observed Vetrano et al.53 compared 2 platelet-rich
(ACL) Reconstruction in patients treated with platelet-rich plasma injections (Kaylight MyCells)
Although ACL reconstruction has tradi- plasma at the graft-tibial tunnel interface given 2 weeks apart with 3 sessions of
tionally been considered a successful pro- at 4 to 6 weeks. However, no differences focused extracorporeal shock-wave
cedure that allows patients to return to the were observed at later time points. therapy. Both patient groups underwent
same-level competition, the ultimate an exercise program. Outcome measures
function of the graft is dependent on a Additionally, the majority of included the VISA, VAS, and modified
complex biologic process of cellular repo- studies have not indicated any clinical Blazina scale53. The platelet-rich plasma
pulation and revascularization, followed improvement in knee stability or out- group showed superior improvement
by progressive matrix remodeling and come scores with the use of adjunctive compared with the extracorporeal
maturation. In addition to these processes platelet-rich plasma during ACL shock-wave therapy group with regard
within the midsubstance of the ACL graft, reconstruction39,41,47. In a Level-I to VISA and VAS scores at 6 and 12
healing also needs to occur between the study, Nin et al.41 randomized 100 pa- months and the modified Blazina scale
graft and the bone tunnel. Several RCTs tients to patellar tendon allograft ACL score at 12 months. In a prospective,
have evaluated the use of platelet-rich reconstruction with and without a nonrandomized cohort study, Filardo
plasma as a surgical adjunct in ACL re- platelet-enriched gel (noncommercial et al.54 examined 15 patients who had
construction in an attempt to accelerate protocol, type 2A). Gels were sutured undergone nonoperative or surgical
graft remodeling and maturation39-41. into the allograft and were applied in the treatment that had failed; these patients
Faster graft maturation as measured by tibial tunnel. At a mean follow-up of subsequently underwent 3 platelet-rich
MRI signal intensity has been demon- 2 years, there were no significant differ- plasma injections (noncommercial pro-
strated in several studies using supple- ences between groups in any clinical and tocol, type 2A) at 15-day intervals. These
mentary platelet-rich plasma during ACL radiographic parameters, including the patients were compared with a control
reconstruction39,42,43. Sa´nchez et al.44 visual analog scale (VAS) for pain, In- group who had not undergone any prior
evaluated patients who underwent ACL ternational Knee Documentation treatment. No significant differences be-
reconstruction with and without adjunct Committee (IKDC) score49, anterior tween groups were observed in either pain
platelet-rich plasma (BTI prgf) and ob- laxity measured by the KT-1000 ar- or VISA scores at 6 months after inter-
tained biopsy specimens from grafted thrometer (MEDmetric), and appear- vention. Larger-scale studies are needed to
tendons during a second-look arthroscopy ance on radiographs and MRI. determine whether platelet-rich plasma
between 6 and 24 months postoperatively. injections are an appropriate treatment
Both gross morphology and histologic Patellar Tendinopathy modality for patellar tendinopathy.
evaluation of the grafts demonstrated im- To our knowledge, there have been only
provements in graft remodeling and more 2 RCTs comparing platelet-rich plasma Knee Osteoarthritis
newly formed connective tissue envelop- with control interventions for refractory The currently available Level-I or II
ing the graft in patients treated with patellar tendinopathy. In a double-blind studies comparing intra-articular
platelet-rich plasma. The authors theo- study of 23 patients, Dragoo et al.50 platelet-rich plasma injections with
rized that this connective tissue envelope is compared a single platelet-rich plasma hyaluronic acid injections or placebo
eventually integrated in the remodeled injection (Biomet GPS III) with dry controls for knee osteoarthritis have
tendon graft. However, the biomechanical needling combined with eccentric exer- shown promising results with the use of
cise. At 12 weeks, the treatment failed in
3 patients in the control group; these

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platelet-rich plasma55-61. Its mechanism were no significant differences between sample size was small. Krogh et al.65
of action seems to be through immu- groups that received 1 injection or 2 in- compared treatment with a single
nomodulation and production of anti- jections. In another RCT, Filardo et al.62 platelet-rich plasma (Biomet GPS II)
inflammatory mediators rather than compared 3 weekly injections of platelet- injection with that with a saline solution
direct modification of the cartilage58,60. rich plasma (noncommercial protocol, type injection in 24 patients. After 3 months,
Thus, much like a corticosteroid injec- 2A) with injections of hyaluronic acid in no differences were observed between
tion, symptomatic relief after platelet- 192 patients with knee osteoarthritis. Sub- groups in the VISA score or pain at rest,
rich plasma injection may be consistent jective outcomes measured included IKDC while walking, and when the tendon was
but only temporary. A meta-analysis by subjective scores, Knee injury and Osteo- squeezed. However, the majority of pa-
Riboh et al.57 revealed superior Western arthritis Outcome Score (KOOS), tients dropped out of the study at 3
Ontario and McMaster Universities EuroQol VAS, and Tegner scores. Both months. Future well-designed RCTs
Osteoarthritis Index (WOMAC) scores treatment groups reported significant im- with larger sample sizes are needed to
in patients treated with leukocyte- provements in function and symptoms ultimately conclude if platelet-rich
reduced platelet-rich plasma compared according to all subjective scores used (p , plasma deserves a role in the treatment
with those treated with hyaluronic acid, 0.0005), but comparative analysis demon- of chronic Achilles tendinopathy.
although no such difference was found strated no differences betweengroups at any
in patients treated with leukocyte-rich follow-up time point. Additionally, the Fractures and Delayed Unions
platelet-rich plasma. Recently, Smith56 platelet-rich plasma group reported more or Nonunions
conducted a U.S. Food and Drug pain and swelling immediately after the Platelet-rich plasma has demonstrated
Administration (FDA)-sanctioned, injection; this pain was possibly related to osteogenic properties in several in vitro
double-blind RCT comparing 3 weekly the leukocyte-rich composition of the and preclinical studies, as shown in a re-
platelet-rich plasma injections (Arthrex platelet-rich plasma used. Despite the het- view by Iqbal et al.66. As a result, several
ACP) with saline solution injections in erogeneity among studies, the majority of RCTs have examined the use of platelet-
30 patients. Improvement in WOMAC published data suggest superior sympto- rich plasma in the setting of acute traumatic
scores in the platelet-rich plasma group matic relief with the use of leukocyte- fractures or iatrogenic osteotomy67-70.
was superior to that in the placebo group reduced platelet-rich plasma in patients However, in the majority of these
from 2 weeks to 1 year after intervention. with early knee degenerative changes com- studies, platelet-rich plasma was used in
At 1 year, WOMAC scores for the pared with hyaluronic acid or placebo, and conjunction with other augments (e.g.,
platelet-rich plasma group improved by itsusemay beconsideredinthis population. bone graft, bone marrow concentrate),
78% from the baseline scores, whereas making it difficult to ascertain the relative
scores for the placebo group improved Achilles Tendinopathy contribution of platelet-rich plasma. In a
by only 7%. In an RCT of 65 patients, A few small RCTs have evaluated the study of 30 patients with distal radial
Simental-Mend´ıa et al.58 compared effects of platelet-rich plasma injection fractures, Namazi and Mehbudi69 com-
treatment with 3 injections of platelet- treatment for chronic midsubstance pared a single intra-articular injection of
rich plasma (noncommercial protocol, Achilles tendinopathy63-66. In the larg- platelet-rich plasma (Arthrex ACP) im-
type 4B) at 2-week intervals with treat- est RCT to date, to our knowledge, 54 mediately after percutaneous pinning
ment with acetaminophen (500 mg patients received eccentric exercise fixation with percutaneous fixation alone.
every 8 hours) over 6 weeks. The platelet- therapy in combination with a single The platelet-rich plasma group reported
rich plasma group reported greater platelet-rich plasma (Biomet GPS III) or better improvement in pain and activity
improvements in all subscores of the saline solution injection63. Although scores compared with the control group at
WOMAC (stiffness, pain, and func- VISA scores and tendon structure and 3 and 6 months. Wrist flexion and ex-
tional capacity) compared with those neovascularization as measured by color tension motion was also better in the
treated with acetaminophen at 6, 12, Doppler ultrasonography improved in platelet-rich plasma group compared
and 24 weeks. Finally, in a study by Patel both groups after 12 weeks, there were with the control group at 3 months, al-
et al.55, 78 patients (156 knees) were no significant differences between though there were no significant differ-
treated with a single injection of platelet- groups. In a pilot study of 20 patients, ences between groups at 6 months.
rich plasma (noncommercial protocol, Kearney et al.64 compared platelet-rich Griffin et al.68 evaluated the use of
type 4B), 2 injections of platelet-rich plasma injection (EmCyte GenesisCS) platelet-rich plasma (EmCyte Gene-
plasma spaced 3 weeks apart, or a single with an eccentric loading program. sisCS) applied during closed reduction
injection of normal saline solution. Both Outcome measures included the VISA and cannulated screw fixation of 200
platelet-rich plasma groups reported sig- and EuroQol-5D (EuroQol-5 Dimen- patients with femoral neck fractures.
nificant improvement in all WOMAC sions). No significant differences were Platelet-rich plasma was injected through
subscores (p , 0.05), and the control noted between groups during the first the cannulated screws into the fracture
group reported no improvement. There 6 months after injection, although the site prior to final tightening and

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compression. A regression analysis well as increased bone apposition on the construct and supplemental use of bone
adjusting for sex, fracture displacement, chips on histomorphometric analysis graft occurred in the majority of patients
dementia, and age revealed no significant (p # 0.03). Radiographs also revealed a in each group. Significantly higher
effect of platelet-rich plasma on the rate of significantly higher rate of osseointegra- clinical and radiographic union rates and
reoperation compared with controls. tion in Groups A and B than in Group C shorter healing times were observed in
Additionally, there were no significant (p , 0.005). However, meaningful clin- the BMP-7 group compared with the
differences in radiographic nonunion or ical improvement was not evaluated. platelet-rich plasma group (p 5 0.016).
osteonecrosis between groups. Dallari Currently, there is limited clinical evi-
et al.67 conducted a trial of 33 patients The majority of studies evaluating dence supporting the use of platelet-rich
undergoing high tibial osteotomy ran- the use of platelet-rich plasma for plasma in bone-healing applications.
domized to 3 groups: lyophilized bone delayed unions or nonunions of long
chips with platelet gel (noncommercial bones consist of small case series71-73. In Conclusions
protocol, type 1A) (Group A), lyophilized the lone RCT of 120 patients, Calori Platelet-rich plasma therapies have the
bone chips with platelet gel and bone et al.74 compared augmentation with ability to locally deliver high concen-
marrow stromal cells (Group B), and platelet-rich plasma (noncommercial trations of biologic factors essential to
lyophilized bone chips alone (Group C). protocol, type 1A) with augmentation the healing process to augment muscu-
In comparison with Group C, Groups A with recombinant bone morphogenetic loskeletal tissue repair. Many of these
and B demonstrated significantly in- protein 7 (BMP-7) applied during the platelet-derived growth factors have
creased osteoblasts and osteoid areas, as revision surgical procedure of long bone been shown to improve tendon and
nonunions. Revision of the fixation

TABLE II Summary of Clinical Studies on Platelet-Rich Plasma Use in Orthopaedic Surgery

Condition or Procedure Clinical Summary

Rotator cuff repair A meta-analysis of 8 Level-I studies and 3 Level-II studies showed no differences in overall gain
UCL injuries in outcome scores or retear rates8. More studies are needed to evaluate whether platelet-rich
Lateral epicondylitis fibrin matrix applied at the tendon-bone interface decreases retear rates.

Hamstring injuries There are currently no comparative studies, to our knowledge.
ACL reconstruction
Six months after the use of Biomet GPS III (type 1A), 1 RCT showed superior improvement in
Patellar tendinopathy pain with resisted wrist extension when compared with dry needling31, 1 RCT showed early
pain reduction but no later differences when compared with autologous blood injection34,
Knee osteoarthritis and 2 RCTs (on same patient population) showed superior reduction in pain and
Achilles tendinopathy improvement in DASH scores when compared with corticosteroid injections27,29. Future
Fractures and delayed unions or nonunion studies should clearly delineate the effects of platelet-rich plasma from the natural course of
tendon healing and symptom resolution.

Two RCTs showed no differences in return to play, reinjury rate, or subjective scores when
compared with saline solution injection35,37. One RCT showed earlier time to return to play
when compared with rehabilitation alone36.

Two RCTs showed accelerations in graft remodeling and maturation39,40. However, the
biomechanical and clinical implications are unclear. Five RCTs showed no improvement in
tunnel healing or decreased tunnel widening39,42,45,47,48. Five RCTs showed no differences in
knee stability or outcome scores39-41,45,47.

One RCT showed no differences in VISA, VAS, Lysholm knee scale, and Tegner activity scale
scores when compared with dry needling at 6 months50. One RCT showed superior
improvement in VISA, VAS, and modified Blazina scale scores when compared with
extracorporeal shock-wave therapy at 12 months53.

With the use of leukocyte-poor platelet-rich plasma, 3 RCTs showed superior outcome scores
when compared with hyaluronic acid or saline solution injection55,56,59.

Four RCTs showed no differences in outcome scores when compared with saline solution
injection or rehabilitation alone63-65.

One RCT showed superior pain and activity scores in patients undergoing percutaneous
fixation of distal radial fractures69. Two RCTs showed no differences in reoperation rate,
radiographic nonunion, or osteonecrosis in patients undergoing closed reduction and
cannulated screw fixation of femoral neck fractures68,70. One RCT showed inferior clinical and
radiographic union rates and longer healing times in the treatment of long bone nonunions
when compared with supplemental use of BMP-774.

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bone healing in animal studies66,75. microstructural and molecular levels, rich plasma may not be enough. Rather,
Although there is a general belief that we also need further information about including an exogenous cell source or
platelet-rich plasma has great promise the nociceptive factors that actually cell recruitment factors may also be re-
and potential to stimulate biologic ac- lead to symptoms. This information quired. Similarly, filtering out unwanted
tivity in difficult-to-heal musculoskele- will provide insight into the biologic factors may be necessary to optimize the
tal tissue, translating these therapies factors that we can try to target with the healing milieu or to drive undifferenti-
into clinically meaningful treatment has next generation of platelet-rich plasma. ated cells down desired pathways within
thus far been met with mixed success. This type of information will help to certain tissues. Given the inter-subject
define how or if platelet-rich plasma can and intra-subject variability in platelet-
The inconsistent results from be both symptom-modifying and rich plasma composition with our
clinical studies (Table II) can partially be structure-modifying. current separation techniques, slight
attributed to the lack of understanding manipulations of the product may be
of the optimal platelet-rich plasma for- In addition to understanding the required to achieve a consistent thera-
mulation for different tissues and pa- pathophysiology of the tissues being peutic effect.
thologies. It may be naive of us to think treated, the other side of the equation is
that the same type of platelet-rich plasma to further characterize the numerous Further progress in this field will
would work for a degenerative rotator components in platelet-rich plasma. In come from studies that correlate the
cuff tear or a hamstring muscle strain addition to the numerous cytokines and biologic activity and components of
or as an adjunct for articular cartilage other factors contained in the alpha platelet-rich plasma with clinical out-
repair. These are all very different tissues granules and dense granules of platelets, come. Because of the tremendous inter-
with different biologic requirements. there are a number of proteins and other individual variability in platelet-rich
In fact, in the current platelet-rich active biologic mediators in the plasma plasma preparations, the optimal way
plasma literature, studies demonstrat- component. The content, concentra- to further study this area would be to
ing a positive effect for lateral epicon- tion, and biologic activity of these vari- characterize the platelet-rich plasma de-
dylitis were more likely to use a ous mediators likely differ between livered to a specific patient. The chal-
leukocyte-rich formulation27,29,31, different platelet-rich plasma prepara- lenge is in defining the relevant factors to
whereas those demonstrating a positive tions. As we learn more about the myriad measure in a given platelet-rich plasma
effect for knee osteoarthritis were more components in platelet-rich plasma, we sample. The field would benefit from
likely to use a leukocyte-reduced can ultimately attempt to refine it by identification of sentinel markers of the
formulation55,56,58. Even within a spe- adding or subtracting factors to tailor biologic activity of platelet-rich plasma
cific tissue, there are likely very different its use for specific clinical needs. For that could be measured efficiently and
biologic requirements depending on instance, if there is a paucity of available cost-effectively in a given aliquot of
patient-related factors (age, smoking cells in the tissue, just adding platelet- platelet-rich plasma. This information
status, underlying medical conditions)
and acute injury compared with chronic TABLE III Grades of Recommendation for Platelet-Rich
injury. Plasma Treatment*

Improved understanding of the Condition or Procedure Grade
underlying structural and composi-
tional deficiencies of the injured tissue Rotator cuff repair C
will help to identify the biologic needs UCL injuries I
that can potentially be targeted with Lateral epicondylitis C
platelet-rich plasma. We need contin- Hamstring injuries C
ued research to further delineate the ACL reconstruction C
cellular and molecular mechanism(s) Patellar tendinopathy C
of degeneration and repair of various Knee osteoarthritis B
orthopaedic tissues, including menis- Achilles tendinopathy C
cus, tendon, cartilage, muscle, and Fractures and delayed unions or nonunions C
bone. Improved understanding of
the basic pathophysiology of these tis- *Grade A indicates good evidence (Level-I studies with consistent findings) for or
sues will come from use of more ap- against recommending intervention. Grade B indicates fair evidence (Level-II or III
propriate animal models, as well as studies with consistent findings) for or against recommending intervention. Grade
examination of tissue samples C indicates conflicting or poor-quality evidence (Level-IV or V studies) not allowing
from patients with well-characterized a recommendation for or against intervention. Grade I indicates that there is insuf-
phenotypes. In addition to under- ficient evidence to make a recommendation.
standing the abnormalities at the

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| Platelet-Rich Plasma in Orthopaedic Surgery

about the actual platelet-rich plasma and author’s perspective. J Cutan Aesthet Surg. 16. Weber SC, Kauffman JI, Parise C, Weber SJ,
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then be correlated with that patient’s management of arthroscopic repair of the
clinical outcome, thus providing deeper 4. Mazzocca AD, McCarthy MB, Chowaniec DM, rotator cuff: a prospective, randomized,
insight into the mechanism of action, Cote MP, Romeo AA, Bradley JP, Arciero RA, double-blinded study. Am J Sports Med. 2013
potential, and limitations of platelet-rich Beitzel K. Platelet-rich plasma differs according Feb;41(2):263-70. Epub 2012 Nov 30.
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Ackland T, Joss B, Zheng M, Breidahl B. Do
In summary, the lack of standard- 5. McCarrel TM, Minas T, Fortier LA. postoperative platelet-rich plasma injections
ization among studies with regard to Optimization of leukocyte concentration in accelerate early tendon healing and functional
platelet-rich plasma preparation, ad- platelet-rich plasma for the treatment of recovery after arthroscopic supraspinatus
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