Review Efficacy of platelet-rich plasma in oral surgery and medicine

Transcription

Oral Surgery & Medicine
Page 1 of 5
Review
Abstract
I Zollino1, V Candotto1, FX Silvestre2, D Lauritano3*
Introduction
Advancements in medicine demand
less invasive therapies and faster recovery times for large-area skin damage caused by burns, large ulcers and
tumours. To cover the wound and aid
in the recovery process platelet-rich
plasma is often used as adjuvant for
skin grafting. Platelet-rich plasma is
a growth factor–enriched with platelet concentrate–and is obtained from
whole autologous blood by using
density-gradient centrifugation. The
platelet concentration of plateletrich plasma is four times higher than
that of whole blood. Platelets when
activated can induce the production
of a variety of growth factors, such as
platelet-derived growth factor, transforming growth factor Î², epidermal
growth factor and vascular endothelial growth factor. As such, plateletrich plasma contains not only high
levels of platelets but also the full
complement of clotting factors.
Preparation of platelet-rich plasma is
quick, simple and relatively inexpensive. Moreover, because platelet-rich
plasma is prepared from the patient’s
own blood, the risk of experiencing
complications is minimal.
* Corresponding author
Email: dorina.lauritano@unimib.it
University of Ferrara, Resident, Maxillo-facial
surgery specialist, Department of Morphology, Surgery and Experimental Medicine,
University of Ferrara, via Luigi Borsari 46,
Ferrara, Italy
2
University of Valencia, Full Professor, University of Valencia Unidad de Estomatologia,
Hospital Dr. Peset, Consultas Externa Jaun De
Garay Sin 46017 Valencia, Spain
3
University of Milan-Bicocca, Assistant Professor, Neuroscience Department, via Cadore
n°48, 20052, Monza (MB), Italy
1
The aim of this review is to discuss
the efficacy of platelet-rich plasma in
oral surgery and medicine.
Conclusion
Since platelet-rich plasma is a vehicle of mitogenic and chemotactic cytokines and growth factors, it shows
to posses beneficial effects for several clinical applications and makes
its use more attractive than the use
of a single-recombinant growth
factor. However, much of the existing published data on platelet-rich
plasma have few laboratory studies documenting the content of the
platelet-rich plasma, mechanism
of action or short- and long-term
outcomes.
Introduction
Advancements in medicine demand
less invasive therapies and faster recovery times for large-area skin damage caused by burns, large ulcers and
tumours. To cover the wound and aid
in the recovery process, skin grafting
is often used. The materials for skin
grafting has gradually developed
from autogenous skin, allogenous
skin and even xenoskin to synthetic
skin substitute, which was made using the ‘tissue-engineered skin’1,2.
Currently, to continue to offer the
best treatments available, the major avenues being explored are stem
cells, gene therapy and autologous or
bioengineered cytokines. However,
these therapies are not yet ready for
widespread clinical use3. So, intense
research in regenerative medicine is
towards accelerating the healing process using various biological agents
such as growth factors (GFs) that
may improve the biological activity
of graft substitutes4 promoting the
repair of skin wounds.
Because platelet-rich plasma
(PRP) is a GF–enriched with platelet
concentrate–it could be promising in
this effort. It is obtained from whole
autologous blood by using density–
gradient centrifugation. The platelet
concentration of PRP is four times
higher than that of whole blood5 and
on activation, platelets can induce the
production of a variety of GFs such,
as platelet-derived GF (PDGF-AB),
transforming GF β (TGF-β), epidermal GF (EGF) and vascular endothelial GF VEGF6,7. As such, PRP contains
not only high level of platelets but
also the full complement of clotting
factors. Preparation of PRP is quick,
simple and relatively inexpensive.
Moreover, because PRP is prepared
from the patient’s own blood, the
risk of experiencing complications is
minimal3.
Biological properties of plateletrich plasma
PRP is an autologous concentration
of platelets in a small volume of plasma8,9. Platelets are a rich source of
the complex group of proteins called
GFs involved in natural wound healing and in regeneration of injured
tissues. GFs are active signals for attracting stem cells into the site of
injury and triggering proliferation
of these cells. These GFs have been
shown to be mitogenic for osteoblasts and to stimulate the migration
of mesenchymal progenitor cells10.
Chemotactic and mitogenic stimulation of these mesenchymal stem cells
occurs and leads to an enhancement
of bone repair and regeneration. Degranulation of platelets granules by
proteins such as thrombin causes
them to actively release these factors
and to initiate all wound healing11.
Licensee OA Publishing London 2014. Creative Commons Attribution License (CC-BY)
For citation purposes: Zollino I, Candotto V, Silvestre FX, Lauritano D. Efficacy of platelet-rich plasma in oral surgery and
medicine: an overview. Annals of Oral & Maxillofacial Surgery 2014 Mar 01;2(1):5.
Competing interests: none declared. Conflict of interests: none declared.
All authors contributed to conception and design, manuscript preparation, read and approved the final manuscript.
All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure.
Efficacy of platelet-rich plasma in oral surgery and
medicine: an overview
Page 2 of 5
Review
Objectives
A search on PubMed database was
performed considering the literature
from 2000 to 2012, using the following key words: PRP, wound healing,
bone regeneration, dental surgery,
oral surgery, tooth extraction, periodontal surgery and implant surgery.
After abstracts screening, the full
texts of selected papers were analysed and the papers found from the
reference lists were also considered.
The search focused on clinical applications documented in studies in the
English language: levels of evidence
included in the literature analysis
were I, II and III. Literature analysis
showed 35 papers that fulfilled the
inclusion criteria: 12 randomised
controlled trials, 4 comparative studies, 10 case series and 9 case reports.
Figure 1: System-vacutainer needle butterfly.
and minimally invasive procedure.
After screwing the needle on the vacutainer butterfly, the tube is inserted in the system-vacutainer needle
butterfly (Figure 1). About 9 mL of
venous blood are collected from the
patient.
Thanks to this vacutainer, blood
volume enters in the tube containing the anti-coagulant acid-citrate
extrose-A (sodium citrate), necesd
sary for the division between the
serum PRP and the packed cells of the
blood. The tube is centrifuged for 15
min at 2200 rcf in a pre-setted speed
and timer centrifuge
equipment
(Figure 2).
After centrifugation, following
three phases can be observed in the
tube (Figures 3 and 4):
Discussion
Obtainment of autologous
platelet-rich plasma
Autologous PRP, useful for tissue
healing and regeneration, is obtained from patient with a simply
Figure 2: Centrifuge equipment.
The platelets GFs include three isomers of the PDGF-AA, PDGF-BB and
PDGFAB, two isomers of the TGF-A1
and TGF-A2, the VEGF and the EGF8.
Moreover, PRP contains adhesive
proteins such as vitronectin (in the >
granules of platelets), fibrin (in plasma) and fibronectin (in plasma)12.
These factors can work both alone
and synergistically to adhere to the
wounded area in early stages of trauma, providing a good basis for wound
repair and shortening repair time1.
So, by applying PRP alone or in combination with a bone graft, the concentration of the GFs and cell adhesion molecules will increase locally
in the area of the bone defect, which
seems to lead to faster and more effective bone regeneration13, while
the handling of the particulate bone
grafts is significantly improved14.
This review gives an overview of the
efficacy of PRP in oral surgery and
medicine.
Page 3 of 5
(Figure 5), is a natural derivative of
the patient’s blood, enriched with
platelets from an average of 232,000
to 785,000 units (about four times
of the standard concentration in the
blood) (Figure 6).
The fraction enriched with GFs
PRP, about 4 mL, is extracted by a
sterile disposable syringe and reinjected into the patient.
Figure 3: Phase of separation after
centrifugation.
• a layer of clear fluid (platelet-poor
plasma);
• a thin layer (1–2 mm) of the
‘buffy coat’ (platelet concentrate)
with platelet-rich liquid, PRP and
• finally, the red phase made from
the cellular fraction of blood.
The ‘buffy coat’ (leuco-platelet
layer) is the fraction of blood that
contains most of the white blood
cells and platelets. Autologous PRP,
obtained after centrifugation of the
tube in the presence of a gel separator
Tissue engineering
Understanding the biology of the
wound healing process has made
possible new expectation about biotechnological composites, possibly
including cell, GFs and scaffolds.
The platelets can act as scaffolds,
providing surfaces for the accumulation of GFs and chemokines. GFs
and chemokines work synergistically
in promoting wound repair. PDGF
stimulates the growth of endothelial
cells, increase the number of fibroblasts in the wound and promote
the differentiation of neutrophils
and monocytes. This factor and TGF
stimulate the formation of capillaries, increase the production of collagen and promote granulation. Particularly, through the stimulation of
epithelial cells, TGF-α upregulates
the proliferation and migration of keratinocytes. Moreover, in the process
Figure 4: Scheme of different fractions of plasma after centrifugation.
of wound healing, TGF-β promotes
collagen synthesis15 and participates
in the inflammatory responses and
in the stimulation of extracellular
matrix synthesis with PDGF. EGF induces chemotaxis and proliferation
of keratinocytes and fibroblasts with
the collagen production. VEGF stimulates the proliferation of endothelial
cells, thereby inducing formation of
new vessels, increasing permeability of existing capillary vessels and
providing nutrients for cell growth
and angiogenesis. Insulin-like GF
(IGF), through IGF-1 and IGF-II, act
as chemotaxic agent for vascular endothelial cells. They stimulate the migration of vascular endothelial cells
towards the wounded area, promote
angiogenesis, and, together with
PDGF, increase the rate of regeneration of endothelium and epidermis16.
Clinical application
Despite a recent explosion of clinical interest in PRP, the concept of
harnessing a patient’s own blood to
facilitate healing has existed since
the early 1980s17. Currently, proponents of PRP believe that it will not
only expedite the healing process but
also improve the quality of the damaged tissue.
Generally, the clinical use and
the benefits of PRP may enable patients to increase the hard- and softtissue wound healing with shorter
recovery times, decrease of postoperative infection, oedema, ecchymosis, blood loss and pain during
recovery3,18–20.
Several publications report the
use of PRP for different clinical
applications, including periodontal21
and oral surgery (e.g. implantology)5,22, maxillofacial surgery (e.g.
jaw reconstruction surgery)8, aesthetic plastic surgery (e.g. cleft palate
surgery, soft-tissue defects and combination with fat grafting)25,26, orthopaedic surgery (e.g. treatment of
chronic tendinopathy, tennis elbow,
anterior cruciate ligament repair,
rotator cuff repair, Achilles tendon
Review
Page 4 of 5
Figure 5: Autologous PRP after centrifugation. PRP, platelet-rich plasma.
Moreover, because GFs promote the
tissue regeneration, clinically they
have been applied in the treatment of
chronic wounds32, soft tissue damage,
bone defect, wrinkle elimination, and
acute trauma. Crovetti et al.33 found
better and faster growth of granulation and epithelial tissues for healing
cutaneous chronic wounds after PRP
application. In plastic surgery and orthopaedics, PRP through PDGFs can
even reduce the chance of secondtime surgery and the occurrence of
osteomyelitis, giving them good prospects of development in these fields1.
Conclusion
As PRP is a vehicle of mitogenic and
chemotactic cytokines and GFs, it
shows to possess a beneficial effect
for several clinical applications and
makes its use more attractive than
the use of a single recombinant GF.
However, much of the existing published data on PRP have few laboratory studies documenting the content of the PRP, mechanism of action
or short- and long-term outcomes.
Abbreviations list
Figure 6: PRP ready for clinical use.
PRP, platelet-rich plasma.
repair, muscle injuries, bone injuries)3 and spinal fusion27,28, cardiac
surgery (e.g. sternal closure and haemostasis of graft harvest site, heart
bypass surgery)29 and treatment of
soft-tissue ulcers21,30. Particularly,
because diabetes is by far one of the
most critical areas for difficult ulcers
to be healed, diabetic ulcers were
those lesions where PRP was firstly
challenged for31.
EGF, epidermal growth factor; GF,
growth factors; IGF, insulin-like
growth factor; PDGF, platelet-derived
growth factor, PPP, platelet poor plasma; PRP, platelet-rich plasma; TGF,
transforming growth factor; VEGF,
vascular endothelial growth factor.
References
1. Han T, Wang H, Zhang YQ. Combining platelet-rich plasma and tissue-engineered skin in the treatment of large
skin wound. J Craniofac Surg. 2012
Mar;23(2):439–47.
2. Liu T, Jin Y. Development of tissue
engineering dermal materials without cells. Guo Ji Sheng Wu Xue Zha Zhi.
2006;29(2):170–73.
3. Wroblewski AP, Mejia HA, Wright VJ.
Application of platelet-rich plasma to
enhance tissue repair. Oper Tech Orthop.
2010 Jun;20(2):98–105.
4. Misch CM. Autogenous bone: is it still
the gold standard? Implant Dent. 2010
Oct;19(5):361.
5. Marx RE, Carlson ER, Eichstaedt RM,
Schimmele SR, Strauss JE, Georgeff KR.
Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod. 1998
Jun;85(6):638–46.
6. Zhang CQ, Yuan T, Zeng BF. Experimental study of effect of platelet-rich plasma
in repair of bone defect. Zhongguo Xiu
Fu Chong Jian Wai Ke Zha Zhi. 2003 Sep;
17(5):355–8.
7. Weibrich G, Hansen T, Kleis W, Buch
R, Hitzler WE. Effect of platelet concentration in platelet-rich plasma on periimplant bone regeneration. Bone. 2004
Apr;34(4):665–71.
8. Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac
Surg. 2004 Apr;62(4):489–96.
9. Arora NS, Ramanayake T, Ren YF, Romanos GE. Platelet-rich plasma: a literature
review. Implant Dent. 2009 Aug;18(4):
303–10.
10. Pieri F, Lucarelli E, Corinaldesi G, Iezzi
G, Piattelli A, Giardino R, et al. Mesenchymal stem cells and platelet-rich plasma
enhance bone formation in sinus grafting: a histomorphometric study in minipigs. J Clin Periodontol. 2008 Jun;35(6):
539–46.
11. Warnke PH, Springer IN, Wiltfang
J, Acil Y, Eufinger H, Wehmöller M, et al.
Growth and transplantation of a custom
vascularised bone graft in a man. Lancet.
2004 Aug–Sep;364(9436):766–70.
12. Marx RE, Garg AK. Dental and craniofacial applications of platelet-rich plasma. Chicago, IL: Quintessence; 2004.
13. Freymiller EG, Aghaloo TL. Plateletrich plasma: ready or not? J Oral Maxillofac Surg. 2004 Apr;62(4):484–8.
14. Arora NS, Ramanayake T, Ren YF, Romanos GE. Platelet-rich plasma in sinus
augmentation procedures: a systematic
literature review: Part II. Implant Dent.
2010 Apr;19(2):145–57.
15. Tamariz-Dominque E, Castro-Muñozledo F, Kuri-Harcuch W. Growth factors and extracellular matrix proteins
during wound healing promoted with
frozen cultured sheets of human epidermal keratinocytes. Cell Tissue Res. 2002
Jan;307(1):79–89.
16. Fu XB, Wang DW. Chuang shang xiu fu
ji chu. 1st ed. Beijing: Ren Ming Jun Yi Chu
Ban She; 1997.pp.129–204.
17. Knighton DR, Hunt TK, Thakral KK,
Goodson WH 3rd. Role of platelets and
fibrin in the healing sequence: an in
Review
Page 5 of 5
vivo study of angiogenesis and collagen
synthesis. Ann Surg. 1982 Oct;196(4):

379–88.
18. Beasley LS, Einhorn TA. Role of growth
factors in fracture healing. In: Canalis E,
editor. Skeletal growth factors. New York,
NY: Lippincott Williams & Wilkins; 2000.
pp.311–22.
19. Anitua E, Andia I, Ardanza B, Nurden
P, Nurden AT. Autologous platelets as a
source of proteins for healing and tissue
regeneration. Thromb Haemost. 2004
Jan;91(1):4–15.
20. Azzena B, Mazzoleni F, Abatangelo G,
Zavan B, Vindigni V. Autologous plateletrich plasma as an adipocyte in vivo delivery system: case report. Aesthetic Plast
Surg. 2008 Jan;32(1):155–8; discussion.
159–61.
21. Liu Y, Kalen A, Risto O, Wahlström O.
Fibroblast proliferation due to exposure
to a platelet concentrate in vitro is pH
dependent. Wound Repair Regen. 2002
Sep–Oct;10(5):336–40.
22. Anitua E. Plasma rich in growth factors: preliminary results of use in the
preparation of future sites for implants.
Int J Oral Maxillofac Implants. 1999
Jul–Aug;14(4):529–35.
23. Della Valle A, Sammartino G, Marenzi
G, Tia M, Espedito di Lauro A, Ferrari F,
Lo Muzio L. Prevention of postoperative bleeding in anticoagulated patients
undergoing oral surgery: use of plateletrich plasma gel. J Oral Maxillofac Surg.
2003 Nov;61(11):1275–8.
24. Whitman DH, Berry RL, Green DM.
Platelet gel: an autologous alternative to
fibrin glue with applications in oral and
maxillofacial surgery. J Oral Maxillofac
Surg. 1997 Nov;55(11):1294–9.
25. Man D, Plosker H, Winland-Brown
JE. The use of autologous platelet-rich
plasma (platelet gel) and autologous
platelet-poor plasma (fibrin glue) in cosmetic surgery. Plast Reconstr Surg. 2001
Jan;107(1):229–37.
26. Welsh WJ. Autologous platelet gel:
clinical function and usage in plastic surgery. Cosmet Dermatol. 2000 Jul;11:13–9.
27. Bose B, Balzarini MA. Bone graft gel:
autologous growth factors used with autograft bone for lumbar spine fusions.
Adv Ther. 2002 Jul–Aug;19(4):170–5.
28. Hee HT, Majd ME, Holt RT, Myers L.
Do autologous growth factors enhance
transforaminal lumbar interbody fusion?
Eur Spine J. 2003 Aug;12(4):400–7.
29. Del Rossi AJ, Cernaianu AC, Vertrees RA, Wacker CJ, Fuller SJ, Cilley JH
Jr, Baldino WA. Platelet-rich plasma reduces postoperative blood loss after
cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1990 Aug;100(2):281–6.
30. Margolis DJ, Kantor J, Santanna J,
Strom BL, Berlin JA. Effectiveness of
platelet releasate for the treatment of diabetic neuropathic foot ulcers. Diabetes
Care. 2001 Mar;24(3):483–8.
31. Wieman TJ, Smiell JM, Su Y. Efficacy
and safety of a topical gel formulation
of recombinant human platelet-derived
growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic
ulcers. A phase III randomized placebocontrolled double-blind study. Diabetes
Care. 1998 May;21(5):822–7.
32. Eppley BL, Woodell JE, Higgins J.
Platelet quantification and growth factor
analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr
Surg. 2004 Nov;114(6):1502–8.
33. Crovetti G, Martinelli G, Issi M, Barone M, Guizzardi M, Campanati B, et al.
Platelet gel for healing cutaneous chronic
wound. Transfus Apheresis Sci. 2004
Apr;30(2):145–51.
Review