Available via license: CC BY-NC 4.0
Content may be subject to copyright.
61
INTRODUCTION
Platelet-derived therapies are a growing trend across
multiple medical and surgical specialties [1-5]. Evidence
suggests that platelets play an important role in tissue
repair, vascular remodeling and inflammatory and immune
Safety and feasibility of platelet rich fibrin matrix
injections for treatment of common urologic
conditions
Ethan L Matz, Amy M Pearlman, Ryan P Terlecki
Department of Urology, Wake Forest Baptist Medical Center, Winston Salem, NC, USA
Purpose: Autologous platelet rich plasma (PRP) is used increasingly in a variety of settings. PRP injections have been used for
decades to improve angiogenesis and wound healing. They have also been offered commercially in urology with little to no data
on safety or efficacy. PRP could theoretically improve multiple urologic conditions, such as erectile dysfunction (ED), Peyronie’s dis-
ease (PD), and stress urinary incontinence (SUI). A concern with PRP, however, is early washout, a situation potentially avoided by
conversion to platelet rich fibrin matrix (PRFM). Before clinical trials can be performed, safety analysis is desirable. We reviewed an
initial series of patients receiving PRFM for urologic pathology to assess safety and feasibility.
Materials and Methods: Data were reviewed for patients treated with PRFM at our center from November 2012 to July 2017. Pa-
tients were observed immediately post-injection and at follow-up for complications and tolerability. Where applicable, Internation-
al Index of Erectile Function (IIEF-5) scores were reviewed before and after injections for ED and/or PD. Pad use data was collected
pre/post injection for SUI.
Results: Seventeen patients were identified, with a mean receipt of 2.1 injections per patient. Post-procedural minor adverse
events were seen in 3 men, consisting of mild pain at injection site and mild penile bruising. No patients experienced complica-
tions at follow-up. No decline was observed in men completing pre/post IIEF-5 evaluations.
Conclusions: PRFM appears to be a safe and feasible treatment modality in patients with urologic disease. Further placebo-con-
trolled trials are warranted.
Keywords: Erectile dysfunction; Penile induration; Platelet-rich fibrin; Platelet-rich plasma; Urinary incontinence, stress
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Original Article - Sexual Dysfunction/Infertility
Received: 3 August, 2017 • Accepted: 10 October, 2017
Corresponding Author: Ryan P Terlecki
Department of Urology, Wake Forest Baptist Medical Center, Medical Center Blvd Winston Salem, NC 27157, USA
TEL: +1-336-716-5690, FAX: +1-336-716-5711, E-mail: rterlecki@wakehealth.edu
ORCID: http://orcid.org/0000-0002-7003-0497
ⓒ The Korean Urological Association
responses through secretion of growth f actors, cytokines and
chemokines [6,7]. These biologically active proteins include
transforming growth f actor-β, platelet-derived growth
factor, platelet-derived epithelial growth f actor, insulin-
like growth f actor, vascular endothelial growth factor, basic
f ibroblast growth f actor, as well as many others [8]. These
www.icurology.org
Investig Clin Urol 2018;59:61-65.
https://doi.org/10.4111/icu.2018.59.1.61
pISSN 2466-0493 • eISSN 2466-054X
62 www.icurology.org
Matz et al
https://doi.org/10.4111/icu.2018.59.1.61
growth factors are implicated in many aspects of natural
wound healing, including chemotaxis, cell prolif eration,
cell dif f erentiation and angiogenesis. They also control
and conduct synthesis, modification and degeneration of
extracellular matrix proteins. Coordination of these cellular
and molecular processes is integral to proper wound healing
and tissue regeneration [9]. The key role of platelets in these
processes makes them an attractive candidate f or therapies
aimed at accelerating natural healing.
One of the most well described platelet-based therapies
is autologous platelet-rich plasma (PRP) [10]. PRP is derived
from the centrif ugation of whole blood with a separator
gel to remove the red and white blood cells. The resulting
supernatant has a greater than f our-f old increase in
platelets and other plasma proteins [11]. This concentrate is
then administered via injection. Newer strategies to prolong
the anti-inf lammatory and wound healing properties of
platelets have focused on creating a f ibrin matrix (platelet
rich fibrin matrix, PRFM) to bind the platelets and prevent
extravasation f rom the site of in jection, thereby addressing
the concern of early washout with PRP [12]. In addition,
PRFM of f ers a potential scaf f old f or tissue ingrowth and
may allow continued release of platelet-related f actors for a
longer duration.
Autologous blood-based biomaterials are promising
therapeutic options f or varied pathology. Rapid generation of
therapeutic material following collection allows for point-of-
care therapy [13]. Furthermore, an autologous therapy avoids
the need f or immunosuppression and eliminates concern of
rejection. Within urology, as with many other specialties,
there are numerous conditions where tissue regeneration is
desirable. In a prior rodent model, Wu et al. [14,15] performed
intracavernosal injection of PRP af ter cavernous nerve
crush injury and noted increased myelinated axons and
improved recovery of erectile f unction. Currently, there are
no reports of PRP or PRFM for the treatment of urologic
conditions in humans, and thus, no assessment of safety. The
aim of this study was to evaluate the safety and feasibility
of PRFM injections in a subset of patients treated f or
erectile dysf unction (ED), Peyronie’s disease (PD), or stress
urinary incontinence (SUI).
MATERIALS AND METHODS
The study was approved by the Institutional Review
Board of Wake Forest School of Medicine (approval
number: IRB00042919). Data was prospectively collected and
retrospectively reviewed f or patients treated with PRFM
for ED, PD, or SUI by a single surgeon f rom November
2012 to July 2017 as part of our novel therapeutics program.
Informed consent was obtained and patients were aware
of off-label use. Demographic data, clinical pathology,
procedural details, outcomes data, and pre- and post-
procedural International Index of Erectile Function (IIEF-
5) questionnaires (f or male patients) were collected. Each
participant was injected with autologous PRFM using a
proprietary system (Selphyl, Aesthetic Factors Inc., Wayne,
NJ, US A ).
1. Preparation and injection process
Venipuncture was performed in the clinic. Two separate
collection tubes were filled with 9 mL of whole blood. The
samples were centrifuged at 6,000 RPMS for six minutes,
and the supernatant was separated f rom the remaining
blood sample using a proprietary system. Ten percent
calcium chloride solution was then added to the PRP in a
1:10 ratio, converting f ibrinogen to fibrin. This process would
generally yield approximately 5.5 mL of injectable PRFM
per tube with patients receiving either 1 or 2 tubes. PRFM,
referred to some as ‘activated PRP’ was chosen so as to
allow better local retention of product and thus avoid early
washout. Administration was performed within ten minutes
of f inal preparation.
Injections were perf ormed based on the targeted
genitourinary pathology. Between 4 and 9 mL of PRFM
was injected per treatment session. Intracavernosal injection
was performed for ED. For patients with PD, an artif icial
erecti on was induced wi th 20 µg of alprostadil to assess
curvature, and injections were placed directly into tunical
plaques under ultrasound guidance. Af ter a thorough
discussion of potential risks and benef its, three patients
elected needle f racture of plaque(s) with concomitant 10
mL saline injection prior to PRFM injections. For SUI, a
pediatric cystoscope and transurethral injection needle were
used to inject PRFM into the urethral submucosa, distal to
the bladder nec k.
Patients were observed in the clinic for 20–30 minutes
post-procedurally for potential complications or side eff ects.
Clinical information, safety related questions, survey data,
and IIEF-5 questionnaires were collected at the time of
clinical follow-up and telephone calls were used to evaluate
for possible adverse events for which no medical attention
was sought.
RESULTS
Seventeen patients underwent injections for the
treatment of organic ED (4), PD (11), coexisting ED with
63
Investig Clin Urol 2018;59:61-65. www.icurology.org
Safety of RPR in urology
PD (1), and f emale SUI (1) (Table 1). Cited reasons for ED
included vasculogenic, penile f racture, medication-related and
electrical injury to the genitalia. Mean patient age at time
of first injection was 46 years (range, 27–61 years). Patients
received an average of 2.1 (range, 1–8) injection procedures
during the study period. Additional injections were provided
upon patient request. Injections were well tolerated in all
cases. Three patients reported mild pain at the in jection
site, one of whom also noted mild penile bruising af ter the
in jecti o n ( Table 2). All patients who noted bruising were PD
patients who were given intracavernosal alprostadil were
also given pla nned i n jecti o n o f 250 µg of phenylephrine at
the conclusion of the procedure to detumescence. No systemic
complications were noted initially or during f ollow-up. Mean
follow-up was 15.5 months.
Among ED and/or PD patients queried with IIEF-5
(7), no patient reported a worsening of overall score or of
any individual domain score. IIEF-5 scores improved by an
average of 4.14 points after PRFM therapy. In patients with
PD with subsequent follow-up, 80% (4/5) initially reported
subjective improvement in their degree of curvature. One
female patient underwent transurethral injection for SUI
with 50% reduction in pad usage. When asked whether they
would be likely to undergo further PRFM in jections, 80% of
patients answered affirmatively.
DISCUSSION
Platelet based therapies are being increasingly utilized
in multiple medical settings, including dermatology,
oph thalmology, cardiology, colorectal surgery, and pla-
stic surgery [1,11]. PRP has been f requently used f or
orthopedic conditions such as bone and sof t tissue trauma,
inf lammatory conditions, and chronic pain syndromes [1,7,10].
Across multiple disciplines, PRP has been used both as a
primary treatment modality and as a supplement to other
therapies in hopes of supplementing wound healing, tissue
regeneration, and angiogenesis. Although most of the studies
focusing on PRP in jections have been relatively small and
heterogenous, they largely support saf ety and ef ficacy.
Additionally, the concept of autologous therapy may be
particularly attractive to some patients [16].
ED af fects as many as 1 in 4 men, and evidence indi-
cates the incidence is rising [17,18]. The pathophysiology is
multifactorial, but a signif icant proportion results f rom
endothelial dysf unction secondary to inf lammation [19]. The
most common treatments f or ED aim to improve endothelial
function through augmentation of the nitric oxide pathway
[20]. To date, there are no treatments that address the un-
derlying cause of endothelial dysf unction. Platelet-derived
therapies targeting inf lammation and promoting tissue
regeneration may represent a potential treatment option.
PD, while less common than ED, af fects roughly 1%–8%
of men [21]. The pathophysiology appears to involve inc-
reased inf lammation f rom tissue disruption, f ollowed by
aberrant wound healing resulting in f i brotic plaques [22].
Current treatment regimens include plaque in jection,
plication, graf ting, or insertion of penile prosthesis to restore
appropriate form and function. Currently there are no
therapies targeting either the inf lammatory processes or
the aberrant wound healing that causes PD. Furthermore,
therapies focusing on disrupting the fibrotic plaques through
mechanical manipulation, or more recently, collagenase
injection, do not address appropriate wound healing or
regeneration of the damaged tissue [23]. Theoretically,
injection of PRFM could combine mechanical disruption
of the plaque, via needle f racture, while simultaneously
neutralizing destructive inf lammatory processes in an effort
to promote a better wound-healing response and stabilize the
disrupted plaque.
Biologic materials have been used f or decades in the
Table 1. Demographic breakdown (n=17)
Demographic Value
Male 16
Female 1
Mean age (y) 46 (27–61)
Mean body mass index (kg/m2) 25.5
Urologic diseases treated
ED 4
PD 11
ED+PD 1
Stress urinary incontinence 1
Mean of injections 2.1 (1–8)
Values are presented as number only or mean (range).
ED, erectile dysfunction; PD, Peyronie’s disease.
Table 2. Demonstrates the minor adverse effect rate (n=17)
Adverse event No. (%)
Minor
Overall 4 (23.5)
Mild pain 4 (23.5)
Bruising 1 (5.9)
Major
Overall 0
Bleeding 0
Infection 0
Compartment syndrome 0
64 www.icurology.org
Matz et al
https://doi.org/10.4111/icu.2018.59.1.61
treatment of SUI. Multiple products ha ve been used as
bulking agents to supplement urethral coaptation. While
generally less eff icacious than surgical repairs, injectable
agents remain attractive given their relative ease of
administration and lack of need f or implantable mesh-based
materials. When it was previously available, glutaraldehyde
cross-linked bovine collagen was the most commonly injected
biomaterial used to treat f emale SUI and was associated
with a cure rate of 53% [24]. Theoretically, in jection of
autologous PRFM could provide both urethral bulking and
potential regenerative effects to a damaged female urethra.
Investigations of PRFM for the urologic conditions noted
in this report have not been previously reported. Wu et al.
[15] investigated the ef f ects of several different preparations
of PRP injections in rat models with bilateral cavernous
nerve crush injuries. Their data suggest that an “optimized”
PRP formulation with a high level of growth factors was
more stable than other preparations of PRP. Rats receiving
this formulation showed significantly greater increases in
intracavernosal pressure, higher mean arterial pressure,
higher levels of nitric oxide synthase, and greater recovery
of erectile f unction than those receiving saline in jections or
other f ormulations of PRP. Tang et al. [25] also showed that
PRP injections at the site of cavernous nerve crush injuries
helped facilitate nerve regeneration and erectile function
in a rat model. More recently, Shirvan et al. [26] described
injection of PRP and interposition platelet rich f ibrin glue
into the fistulous tracts of 12 patients with vesicovaginal
f istulas (most <5 mm). All patients showed signif icant
improvement with 11 patients cured at six-month follow-up,
both subjectively and by examination.
We recognize that a variety of preparations, delivery
modalities, and dosing schedules are available for PRP/
PRFM therapies. A mean of 2.1 in jection procedures per
patient were perf ormed during the study period. In our
study, the PRP was added to a calcium chloride preparation
to create PRFM. This was done to theoretically prevent
rapid washout of the PRP f rom the corpora. One potential
safety concern about using a colloid/hydrogel type of
material in the corpora was the possibility of interrupting
corporal blood flow, creating the possibility of a ‘penile
compartment syndrome,’ akin to priapism. This did not occur
in any of the ED or PD patients in our study, as each of
these injections was well tolerated.
Data f rom this report regarding functional assessments
must be interpreted with caution. This was not a prospective
study, and we believe a signif icant placebo ef fect exists
for research involving male sexual health. Objective
improvements in the IIEF-5 score (4.14 points, 9.1%) were
seen in patients receiving PRFM therapy f or ED and PD.
This level of improvement was similar to the average IIEF
score increase (4.45 points, [3.42, 5.29]) seen in patients using
PDE5Is af ter nerve sparing prostatectomy in a recent meta-
analysis [20]. At f ollow-up interviews, patients expressed
specific improvements in the rigidity of erections and
improvements in satisfaction due to increased conf idence.
Of PD patients available for f ollow-up, 80% noticed an
initial subjective improvement in their degree of curvature.
Additionally, the one patient who received PRFM injections
f or SUI noted a 50% decrement in pad usage. Patients
injected with silicone polymers (Macroplastique, Cogentix,
Minnetonka, MN, USA) reported a 77% subjective cure rate
but only a 9% objective cure rate on urodynamic testing [27].
No conclusions can be drawn f rom a single patient, but a
50% objective improvement from a transurethral injection
procedure using an autologous product seems promising.
With regards to feasibility of the procedure, there were no
concerns related to the preparation of the PRFM or the
injection process itself into the corpora cavernosa, tunical
plaques, or urethral submucosa for patients with ED, PD, or
SUI, respectively.
While this study attests to safety in this selected population,
it has multiple limitations. This was a retrospective review
of a small cohort of patients with a spectrum of pathology
that may not be representative of the general population.
As an autologous product, we expect that reabsorption rates
are high, such that repetitive therapy will be required. This
raises the possibility of treatment-related f ibrosis f rom
injection site trauma. As mentioned, although there was no
detriment in IIEF score, the lack of a placebo arm prevents
a detailed context. Future work will involve placebo control,
with structured assessments for eff icacy.
CONCLUSIONS
Our initial experience suggests that PRFM injections
for ED, PD, and female SUI are f easible and safe. Although
the limited data is suggestive of ef f icacy, a placebo control
will be required in subsequent eff orts f or conf irmation.
Future studies evaluating efficacy of PRFM injections for
genitourinary pathology appear warranted.
CONFLICTS OF INTEREST
The authors have nothing to disclose.
65
Investig Clin Urol 2018;59:61-65. www.icurology.org
Safety of RPR in urology
REFERENCES
1. Andia I, Maffulli N. Platelet-rich plasma for managing pain
and inflammation in osteoarthritis. Nat Rev Rheumatol
2013;9:721-30.
2. Jiritano F, Serraino GF, Rossi M, Dominijanni A, Brescia A,
Renzulli A. Ventricular assist device driveline infection: treat-
ment with platelet-rich plasma. Ann Thorac Surg 2013;96:e37-
8.
3. Marck RE, Middelkoop E, Breederveld RS. Considerations on
the use of platelet-rich plasma, specifically for burn treatment.
J Burn Care Res 2014;35:219-27.
4. Schiavone G, Raskovic D, Greco J, Abeni D. Platelet-rich
plasma for androgenetic alopecia: a pilot study. Dermatol Surg
2014;40:1010-9.
5. Zhou B, Ren J, Ding C, Wu Y, Chen J, Wang G, et al. Protec-
tion of colonic anastomosis with platelet-rich plasma gel in the
open abdomen. Injury 2014;45:864-8.
6. Galliera E, Corsi MM, Banfi G. Platelet rich plasma therapy:
inflammatory molecules involved in tissue healing. J Biol
Regul Homeost Agents 2012;26(2 Suppl 1):35S-42S.
7. Randelli P, Randelli F, Ragone V, Menon A, D’Ambrosi R, Cuc-
chi D, et al. Regenerative medicine in rotator cuff injuries.
Biomed Res Int 2014;2014:129515.
8. Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E. Platelets
and wound healing. Front Biosci 2008;13:3532-48.
9. Werner S, Grose R. Regulation of wound healing by growth
factors and cytokines. Physiol Rev 2003;83:835-70.
10. Xie X, Zhang C, Tuan RS. Biology of platelet-rich plasma and
its clinical application in cartilage repair. Arthritis Res Ther
2014;16:204.
11. Sampson S, Gerhardt M, Mandelbaum B. Platelet rich plasma
injection grafts for musculoskeletal injuries: a review. Curr Rev
Musculoskelet Med 2008;1:165-74.
12. Gigante A, Del Torto M, Manzotti S, Cianforlini M, Busilac-
chi A, Davidson PA, et al. Platelet rich fibrin matrix effects on
skeletal muscle lesions: an experimental study. J Biol Regul
Homeost Agents 2012;26:475-84.
13. Kushida S, Kakudo N, Morimoto N, Hara T, Ogawa T, Mitsui
T, et al. Platelet and growth factor concentrations in activated
platelet-rich plasma: a comparison of seven commercial sepa-
ration systems. J Artif Organs 2014;17:186-92.
14. Wu CC, Wu YN, Ho HO, Chen KC, Sheu MT, Chiang HS. The
neuroprotective effect of platelet-rich plasma on erectile func-
tion in bilateral cavernous nerve injury rat model. J Sex Med
2012;9:2838-48.
15. Wu YN, Wu CC, Sheu MT, Chen KC, Ho HO, Chiang HS. Op-
timization of platelet-rich plasma and its effects on the recov-
ery of erectile function after bilateral cavernous nerve injury in
a rat model. J Tissue Eng Regen Med 2016;10:E294-304.
16. Weiss RA. Autologous cell therapy: will it replace dermal fill-
ers? Facial Plast Surg Clin North Am 2013;21:299-304.
17. Derby CA, Araujo AB, Johannes CB, Feldman HA, McKinlay
JB. Measurement of erectile dysfunction in population-based
studies: the use of a single question self-assessment in the Mas-
sachusetts Male Aging Study. Int J Impot Res 2000;12:197-204.
18. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ,
McKinlay JB. Construction of a surrogate variable for impo-
tence in the Massachusetts Male Aging Study. J Clin Epidemiol
1994;47:457-67.
19. Vlachopoulos C, Aznaouridis K, Ioakeimidis N, Rokkas K,
Vasiliadou C, Alexopoulos N, et al. Unfavourable endothelial
and inflammatory state in erectile dysfunction patients with or
without coronary artery disease. Eur Heart J 2006;27:2640-8.
20. Li J, Shi Q, Pu C, Tang Y, Bai Y, Yuan H, et al. Phosphodiester-
ase type 5 inhibitors for the treatment of post-nerve sparing
radical prostatectomy erectile dysfunction in men. Sci Rep
2014;4:5801.
21. Greenfield JM, Levine LA. Peyronie's disease: etiology,
epidemiology and medical treatment. Urol Clin North Am
2005;32:469-78, vii.
22. Levine LA, Burnett AL. Standard operating procedures for
Peyronie's disease. J Sex Med 2013;10:230-44.
23. Gelbard M, Goldstein I, Hellstrom WJ, McMahon CG, Smith
T, Tursi J, et al. Clinical efficacy, safety and tolerability of colla-
genase clostridium histolyticum for the treatment of peyronie
disease in 2 large double-blind, randomized, placebo con-
trolled phase 3 studies. J Urol 2013;190:199-207.
24. Davis NF, Kheradmand F, Creagh T. Injectable biomaterials
for the treatment of stress urinary incontinence: their poten-
tial and pitfalls as urethral bulking agents. Int Urogynecol J
2013;24:913-9.
25. Tang YQ, Han BM, Yao XQ, Hong Y, Wang Y, Zhao FJ, et al.
Chimeric molecules facilitate the degradation of androgen re-
ceptors and repress the growth of LNCaP cells. Asian J Androl
2009;11:119-26.
26. Shirvan MK, Alamdari DH, Ghoreifi A. A novel method for
iatrogenic vesicovaginal fistula treatment: autologous platelet
rich plasma injection and platelet rich fibrin glue interposition.
J Urol 2013;189:2125-9.
27. Maher CF, O'Reilly BA, Dwyer PL, Carey MP, Cornish A,
Schluter P. Pubovaginal sling versus transurethral Macroplas-
tique for stress urinary incontinence and intrinsic sphincter
deficiency: a prospective randomised controlled trial. BJOG
2005;112:797-801.
