Current Applications of Platelet Gels in Facial Plastic Surgery

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Current Applications of Platelet Gels in

Facial Plastic Surgery


Sumeet Bhanot, M.D.,1 and James C. Alex, M.D.1

ABSTRACT

The response of living tissue to injury is a central component in the planning of


all surgical procedures. The wound-healing process is typically divided into three phases
(inflammatory, proliferative, and remodeling) and is a complex process in which a multi-
tude of cellular and humoral components interact to restore a wound defect. Platelets and
their released cytokines and growth factors are pivotal in the modulation of this entire
process. Although several techniques may be used to achieve hemostasis after initial in-
jury, few initiate and actually accelerate tissue regeneration. Both platelet gel and fibrin
glue are effective hemostatic agents. Platelet gels, unlike fibrin glue, have a high concen-
tration of platelets that release the bioactive proteins and growth factors necessary to ini-
tiate and accelerate tissue repair and regeneration. In particular, two growth factors that
play a major role in platelet gels are platelet-derived growth factor, a powerful chemoat-
tractant, and transforming growth factor , which significantly increases and stimulates
the deposition of extracellular matrix. In creating a platelet gel, autologous blood is cen-
trifuged to produce a concentrate high in both platelets and plasma. This concentrate can
be applied to wounds, providing hemostasis, adhesion, and enhanced wound healing. Re-
cent techniques for the autologous concentrating process have been streamlined, and now
platelet gels are clinically accessible to most physicians. Platelet gels have global applica-
tions in surgery and are especially useful for the soft tissue and bony reconstructions en-
countered in facial plastic and reconstructive surgery. In these applications, their use has
been associated with a decrease in operative time, necessity for drains and pressure dress-
ings, and incidence of complications. When applied to bony reconstruction it provides
adhesion for the consolidation of cancellous bone and comminuted fracture segments.

KEYWORDS: Blood products, platelet gels, tissue sealants, fibrin glue

BASIC SCIENCE OF WOUND HEALING component of the early inflammatory phase (Fig. 1).
Wound healing is a very intricate process involving the The intrinsic pathway is activated when, in the presence
complex interplay of numerous humoral factors and of kininogen and prekallokrenin, factor XII (Hageman
cells. It is divided into three overlapping stages: inflam- factor) comes in contact with collagen and activates
matory, proliferative, and remodeling. The inflammatory factor XI. Activated factor XI in turn activates factor
phase begins with tissue injury, which leads to platelet IX, which, in the presence of activated factor VIII and
aggregation and release of platelet growth factors, cy- calcium, activates factor X. Meanwhile, in the extrinsic
tokines, and hemostatic factors. Both intrinsic and/or pathway, tissue damage results in the release of thrombo-
extrinsic pathways mediate the clotting cascade, a central plastin (formed from phospholipids and glycoproteins),

Recent Biological Advances in Facial Plastic Surgery; Editors in Chief, Fred Fedok, M.D., Gilbert J. Nolst Trenité, M.D., Ph.D., Daniel G.
Becker, M.D., Roberta Gausas, M.D.; Guest Editor, David B. Hom, M.D., FACS. Facial Plastic Surgery, Volume 18, Number 1, 2002.
Address for correspondence and reprint requests: Dr. James C. Alex, Section of Otolaryngology, Yale University School of Medicine, 800 Howard
Avenue, YPB #420, New Haven, CT 06520. 1Section of Otolaryngology, Division of Facial Plastic and Reconstructive Surgery, Yale University
School of Medicine, New Haven, CT. Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Tel: +1(212) 584-4662. 0736–6825,p;2002,18,01,027,034,ftx,en;fps00414x.
27
28 FACIAL PLASTIC SURGERY/VOLUME 18, NUMBER 1 2002

Figure 1 Coagulation pathway. See text for details.

which activates factor VII and subsequently factor X. blood. Attracted by local factors, polymorphonuclear
In the common pathway, factors X and V interact with leukocytes and monocytes migrate out of blood ves-
calcium and convert prothrombin to thrombin. Throm- sels to the site of injury. The monocytes differentiate
bin converts fibrinogen to fibrin monomers and activates into macrophages and along with neutrophils kill and
factor XIII, which then polymerizes the fibrin mono- phagotize bacteria and debris. Thereafter, endothelial
mers by cross-linking them into an organized clot. This cells begin to proliferate and fibroblasts migrate to the
structural matrix allows monocytes, keratinocytes, and injury site, marking the beginning of the proliferative
fibroblasts to adhere to the wound area. phase.
Platelets and other inflammatory cells release a During the proliferative phase macrophages re-
number of cytokines and growth factors. The throm- move debris and bacteria, whereas fibroblasts synthesize
boxane and serotonin released by platelets cause vaso- a ground substance. Under the influence of chemotactic
constriction and consequently aid in hemostasis by growth factors, migrating endothelial cells create new
preventing the dissipation of local tissue factors from blood vessels in the process known as angiogenesis. The
the injury site. At the same time, other areas of the restored blood flow brings necessary nutrients and oxy-
wound are under the influence of histamine, also re- gen for optimal wound healing. Soon more fibroblasts
leased by platelets, which increases vascular permeabil- accumulate and initiate the deposition of an extracel-
ity, allowing entry of additional cells and factors from lular matrix consisting of mainly mucopolysaccharides,
CURRENT APPLICATIONS OF PLATELET GELS/BHANOT, ALEX 29

collagen, and elastin. Epithelialization is also accom- it was possible to produce high concentrations of fi-
plished in this phase, commencing from the edges of brinogen, that the use of fibrin-based tissue adhesives or
the wound. The resulting scar at the end of the prolifer- glues became a reality.
ative phase is then further altered with respect to both Fibrin glue essentially involves the making of
its ground tissue matrix and collagen fibers in the re- concentrated fibrinogen in the presence of factor XIII
modeling phase. In this phase, a mature scar is produced (fibrin stabilizing factor) and pooled plasma proteins
as collagen lysis reaches equilibrium with collagen syn- (fibronectin and cold insoluble globulin). This is then
thesis and the collagen fibers are realigned for optimal combined with thrombin, calcium chloride, and one of
strength. The process of remodeling can take up to 2 three fibrinolysis inhibitors (tranexamic acid, E-amino
years and results in a scar that usually has approximately caproic acid, and aprotinin, of which aprotinin is the
80% the strength of normal skin. most potent). The thrombin cleaves fibrinogen to fi-
To expedite the process of wound healing and brin and activates factor XIII, which cross-links the fi-
minimize edema and scarring, surgeons try to obtain he- brin and forms a clot matrix. Fibrinolysis inhibitors
mostasis and reapproximate the edges of the wound as inhibit plasmin degradation of the clot.6 Fibronectin
close to the preinjury state as possible. Traditionally this anchors the matrix components to the site of injury
has been accomplished by mechanical methods such as and the resulting fibrin cross-linked matrix provides
sutures that physically hold the edges of the wound to- a three-dimensional scaffolding into which undiffer-
gether while an adhesion is formed. More recently tissue entiated cells, such as fibroblasts, can migrate and then
glues have been introduced for this purpose. proliferate.
Fibrinogen can be obtained from a number of
sources, including pooled-donor cryoprecipitate, single-
TISSUE SEALANTS AND GLUES donor cryoprecipitate, or autologous plasma. Due to the
possible risk of viral transmission from the multidonor
Synthetic Sealants product, the FDA ruled against it in 1978.7 Since then,
Cyanoacrylates, which were first described in 1949, are there has been one reported case of HIV transmission
tissue adhesives that polymerize once in contact with from the use of a homologous product.8 This led to the
fluids, solids, or tissues. Earlier shorter-chain monomers development of both single-donor and autologous cryo-
caused inflammatory reactions and therefore were aban- precipitated fibrinogen preparation processes that used
doned in favor of longer-chain monomers such as butyl- multiple freeze/thaw cycles to concentrate the fibrino-
cyanoacrylate that had minimal inflammatory response. gen.9 Although this process produced concentrated fi-
However, this family of cyanoacrylates was brittle and brinogen that was usable for up to 1 year, the process re-
lacked tensile strength. quired several days to complete, making it cumbersome
These shortcomings were addressed by the next and clinically impractical.
generation of cyanoacrylates, the octylcyanoacrylates. Currently, the formation of most tissue glues in-
Octylcyanoacrylates, unlike its predecessors, consist of volves two steps. First, the patient’s whole blood is col-
a combination of a monomer and plasticizers that poly- lected and centrifuged into its plasma and cellular com-
merize to form a flexible and strong bond. Currently, ponents. The plasma is then drawn up into a syringe
octylcyanoacrylate has been approved for topical/ and, in a second step, mixed with bovine collagen and
external use as a wound sealant.1 This sealant offers the thrombin, which act as platelet activators and convert
benefits of good wound edge adhesion with significant the patient’s plasma fibrinogen to fibrin, respectively.
time saving over the use of sutures and avoids issues of However, the quantity and quality of some commercial
suture removal and suture track scarring.1 In addition preparations may produce such a dense architecture that
to providing physical adhesion, certain biological prod- angiogenesis and overall healing is inhibited.10,11 In ad-
ucts contain additional elements that promote rapid dition, the fibrin glue matrix is considered bioactively
wound healing. Among these products are fibrin glue passive in that it does not possess a mechanism to ac-
and platelet gels. tively recruit undifferentiated cells into its scaffolding.
Although these characteristics do not affect the fibrin
clot’s hemostatic properties, they can result in delayed
Fibrin Glue and defective tissue repair.
Fibrin’s adhesive properties were first discovered by
Bergel in 1909, and the application of a fibrinogen de-
rivative in liver and cerebral hemorrhage was first de- Platelet Gels
scribed by Grey in 1915.2,3 This was followed by the Recently, in response to these concerns, platelet gels
work of Cronkite et al. and Tidrick and Warner, who were developed using a new process, differential cen-
combined fibrinogen and thrombin to successfully fix- trifugation, which can rapidly concentrate autologous
ate skin grafts.4,5 However, it was not until 1970, when platelets and fibrinogen from whole blood. In this pro-
30 FACIAL PLASTIC SURGERY/VOLUME 18, NUMBER 1 2002

cess whole blood is centrifuged, and the platelet and


fibrinogen rich plasma component are harvested.12,13
Platelet gels differ from fibrin glue in that they
contain a high concentration of platelets that markedly
improve the adhesive properties and the wound-healing
characteristics when compared with fibrin glue alone.
It has been shown that 55% of the clot strength is due
to the platelets and 45% is due to the fibrin strands.14
Thus, the addition of platelets, which bind to both one
another and to the cross-linked fibrin strands, markedly
improves overall clot strength. However, because the fi-
brin strands in platelet gel are not increased above nor-
mal levels, the matrix structure that is formed has the
same open architecture of a typical blood clot and facili-
tates new capillary in-growth.
Additionally, platelet gels form a bioactive matrix
(Fig. 2A) resulting from the high concentration of
platelets that release multiple growth factors when acti-
vated. These growth factors affect tissue regeneration in
two ways. First, the growth factors actively attract un-
differentiated cells into the matrix (Fig. 2B) where these
cells attach themselves to the matrix’s fibrin strands.
Second, the growth factors then bind to the cell mem-
brane of fibroblasts or other undifferentiated cells, and
through the process of signal transduction they trigger
cell division (Fig. 2C).5,15
In addition to growth factors, platelet gels con-
Figure 2 Schematic representation of cellular components
tain additional proteins considered critical to initiating
involved in platelet gels. (A) Formation of platelet-fibrin matrix tissue regeneration. The plasma contains several adhe-
and release of growth factors from platelets. (B) Chemoat- sion molecules that play a role in facilitating the bind-
traction of stem cells into bioactive matrix, under the influence ing of undifferentiated cells within the clot matrix. The
of platelet-released growth factors. (C) Cellular elements in an
evolving active platelet gel matrix.
platelets also produce signaling proteins that attract
white blood cells. Two of the more important factors

Table 1 Table of Biological Activity of Key Proteins and Growth Factors Required in Wound Healing
Protein Biological Activity Fibrin Glue Clots Platelet Gel

Fibrinogen Promotes hemostasis, provides scaffolding for Yes Yes


undifferentiated cell migration
Adhesion molecules (Fibronectin, Facilitate intercellular binding and communication No Yes
SCF, vitronectin)
Platelets Promote hemostasis; initiate wound-healing cascade No Yes
Platelet protein (IL-1b) Signals lining cells of damaged vessels to display No Yes
receptors for macrophages
Platelet-derived growth factor  Initiate connective tissue healing; increase No Yes
mitogenesis, angiogenesis, and macrophage
activation
Transforming growth factor beta Increases the chemotaxis and mitogenesis of No Yes
osteoblast precursors; stimulates osteoblast
deposition of the collagen matrix of wound healing
and bone regeneration
Epidermal growth factors Induce epithelial development and promote No Yes
angiogenesis
Vascular endothelial growth factors Contain potent angiogenic, mitogenic, and No Yes
vascular permeability-enhancing activities specific
for endothelial cells
CURRENT APPLICATIONS OF PLATELET GELS/BHANOT, ALEX 31

are platelet-derived growth factor (PDGF) and trans- make the PRP solution (approximately 7 cc per sy-
forming growth factor 1 (TGF-1). PDGF is a potent ringe). Both PRP and PPP solutions can then be acti-
chemoattractant and mitogen for fibroblasts, mono- vated by a solution containing 5000 U of topical bovine
cytes, and macrophages. It also activates collagenase, thrombin (Gen Trac, Middleton, WI) and 5 cc of 10%
which fosters remodeling of collagen in the latter stages calcium chloride solution. The systematic combination
of wound healing; PDGF is also thought to play a role and delivery of these two solutions are performed using
in neointimal hyperplasia. TGF- stimulates collagen, a 20G dual-cannula applicator tip (Micromedics, Inc.,
proteoglycan, elastin, and fibronectin synthesis and re- Eagan, MN; Fig. 3). The PPP forms fibrin glue once
duces the expression of collagen and plasmin activa- activated, whereas the PRP produces platelet gel.
tor.6,16 In addition, the platelets release a myriad of The SmartPRePTM process recovers approxi-
other factors that have hemostatic as well as wound- mately 68% of platelets from whole blood and signifi-
healing enhancement capabilities. The biological func- cantly concentrates the growth factors multiple times,
tions of several key proteins are listed in Table 1. specifically PDGF (600%), TFG-1 (727%), VEGF
There is one caveat. Regardless of the method (428%), and EGF (550%).18
for making autologous platelet concentrate, to achieve a Regardless of the surgical procedure, the applica-
bioactive matrix with a platelet gel clot, it is important tion of fibrin glue and platelet gels is fairly constant.
that the platelet concentrate contains viable platelets be- During the operative dissection, fibrin glue (PPP) can
cause only viable platelets release the key growth proteins. be sprayed on exposed tissue surfaces for hemostasis.
When it is time for closure of the wound, a small quan-
tity of gel can be applied to the undersurface of the flap.
A gauze is then rolled along the flap in the direction of
TECHNIQUE the desired vector of lift to spread the gel along the un-
There are a number of different processes described in dersurface and milk out any excess.19 The skin closure
the literature for obtaining platelet gels, all of which can also be sealed with the platelet gel.
involve differential centrifugation of whole blood ob- The use of platelet gels has been associated with
tained prior to any surgical incisions. This is impor- decreased operative times, use of drains and pressure
tant because any incision or wound made prior to dressings, incidence of hematoma and seroma forma-
blood collection activates the patient’s platelets and tion, postoperative edema, and postoperative pain.17
coagulation system and decreases the amount of these There are two other advantages of platelet gels. First,
essential components in the whole blood obtained because platelet gels contain the final components of
thereafter. the coagulation cascade, their use mitigates the effect of
A number of centrifugation devices have been de- any coagulation defects that may occur during surgery
scribed for use in the preparation of platelet-rich plasma or may have gone undetected preoperatively. Second,
(PRP) used for platelet gels and platelet-poor plasma because of their strong hemostatic properties, platelet
(PPP) used for fibrin glue. These include the Med- gels minimize the use of cautery and, therefore, reduce
tronic Electromedic, Elmd-500 Autotransfusion system the risk of nerve injury.
(Parker, CO),6 the Plasma Saver device by Haemonetics
(Braintree, MA),12 and the SmartPRePTM by Harvest
Technologies Corp. (Novell, MA).17
The process used by SmartPRePTM exemplifies APPLICATIONS IN SURGERY
the technique and results in the production of both au- Autologous platelet gels have a number of advantages and
tologous PRP and concentrated fibrinogen (PPP). Prior can be applied to a wide array of surgical procedures. Its
to the start of the operative procedure, a venipuncture general applicability is in part due to its unique wound-
is performed, and 90 to 110 cc of the patient’s whole healing characteristics of hemostasis, tissue adhesion,
blood is drawn up equally between two 60-cc sy- growth factors, and cytokines. Reports thus far have dem-
ringes containing 5 cc of a citrate-based anticoagulant onstrated decreased hematoma formation, seroma forma-
(ACD-A). The content of each syringe is placed in a tion, postoperative swelling, and healing time.17
vial and centrifuged, separating the red blood cells from In facial plastic and reconstructive surgery, the dual
the plasma. Next, while in the centrifuge, the plasma is advantages of fibrin adhesives as hemostatic agents and
siphoned off and then respun, further concentrating the as adhesive agents are underscored by their use with
plasma platelets into a pellet. This fully automated pro- rhytidectomy flaps, upper and lower blepheroplasties,
cess takes approximately 12 minutes. The result is a vial brow flaps, skin grafts, bone graft donor sites, bony recon-
with a pellet consisting of platelets and the supernatant struction, and sutureless closure of incisions.19 Bruck, in
consisting of PPP. Approximately two-thirds (approxi- 1982, reported his experience with the use of fibrin glue
mately 20 cc per syringe) of the supernatant (PPP) is in 82 rhytidectomies and noted a decrease in operative
decanted and can be used for hemostatic purposes. The time and postoperative swelling and an increase in patient
pellet is resuspended in the remaining supernatant to comfort.20 Similarly, in 1994, Marchac reported his expe-
32 FACIAL PLASTIC SURGERY/VOLUME 18, NUMBER 1 2002

Figure 3 Process used to harvest and apply platelet gels (SmartPRePTM).

rience of the use of fibrin glue in 200 rhytidectomies and its hemostatic and adhesive qualities are particularly
observed no change in complications despite the lack valuable.16 Other platelet gel applications include dural
of drains and pressure dressing in all cases.21 Mommaerts, closures, oral–nasal and oral–antral fistulas repairs, and
in 1996, observed no difference in scar morphology when microvascular and microneural anastomosis.6,15,23
comparing 18 patients undergoing blepharoplasty using In bony reconstruction fibrin glue (PPP) has been
only fibrin glue for closure with 12 patients using 5–0 used as a hemostatic agent in ilium bone graft donor
nylon for closure.22 Saltz et al., in 1991, observed increase sites.6 In mandibular reconstruction, platelet gels (PRP)
adherence of split-thickness skin graft, without the use of have been used to reapproximate comminuted bone frag-
a bolster, in 82 patients, which included 51 burns.9 ments in complicated fractures, improving the stability
Fibrin adhesives have been extremely useful in of the repair. Platelet gels also promote the adhesion and
skin graft applications demonstrating improved graft consolidation of particulate cancellous bone and marrow
take, especially after debridement of burn eschar where grafts, making the grafts easier to handle and conform
CURRENT APPLICATIONS OF PLATELET GELS/BHANOT, ALEX 33

into allogenic cribs and alloplastic trays.24 Tayapongsak et 2. Bergel G. Uber Wirkungen des Fibrins. Dtsch Medi
al., in 1994, having used fibrin glue in major mandibular Wochenschr 1909;35:663
reconstruction with autogenous particulate cancellous 3. Grey EG. Fibrin as a hemostatic in cerebral surgery. Surg
Gynecol Obstet 1915;21:452
bone and marrow in 33 patients, demonstrated by radi- 4. Cronkite EP, Lozner EL, Deaver J. The use of thrombin and
ographs that the remodeling phase occurred 50% sooner fibrinogen in skin grafting. JAMA 1944;124:976
than controls (4 vs. 8 weeks).24 Fibrin adhesives have 5. Tidrick RT, Warner ED. Fibrin fixation of skin transplanta-
been also used in a similar fashion in other mandibular tion in skin grafting. Surgery 1944;15:90
reconstructive procedures such as inferior alveolar nerve 6. Whitman DH, Berry RL, Green DM. Platelet gel: an autolo-
lateralization, placement of osseointegrated implants, and gous alternative to fibrin glue with applications in oral
repair of alveolar clefts. In 1998, Davis and Sandor dem- and maxillofacial surgery. J Oral Maxillofac Surg 1997;55:
1294–1299
onstrated the multiple uses of fibrin glue in maxillofacial 7. Revocation of fibrinogen licenses. FDA Drug Bull 1978;8:15
sugery with good outcome and no complications, specifi- 8. Wilson S, Pell P, Donegan EA. HIV-1 transmission fol-
cally applied to 14 patients with bone and alloplastic fix- lowing the use of cryoprecipated fibrinogen as gel/adhesive.
ation, 13 patients with cleft lip and palate repair, and 12 Transfusion 1991:31s:51s
patients with sinus lift procedures for the fixation of bone 9. Saltz R, Sierra D, Feldman D, Saltz MB, Dimick A, Vasconez
grafts and repair of torn mucoperiosteal lining.25 In addi- LO. Experimental and clinical applications of fibrin glue.
tion to the obvious mechanical adhesion benefits with Plast Reconstr Surg 1991;88:1005–1015;1016–1017
10. O’Grady KM, Agrawal A, Bhattacharyya TK, Shah A, Tori-
bony applications, platelet gels provide a rich physiologic umi DM. An evaluation of fibrin tissue adhesive concentra-
milieu for bone healing due to the presence of growth tion and application thickness on skin graft survival. Laryn-
factors and cytokines in the area of reconstruction.6 goscope 2000;110:1931–1935
Other varied surgical applications of platelet gels 11. Byrne DJ, Hardy J, Wood RA, McIntosh R, Cuschieri A.
have been reported. Their use as a biological dressing Effect of fibrin glues on the mechanical properties of healing
after laser resurfacing has demonstrated faster healing wounds. Br J Surg 1991;78:841–843
and decreased erythema.17 The application of platelet 12. Oz MC, Jeevanandam V, Smith CR, et al. Autologous fibrin
glue from intraoperatively collected platelet-rich plasma. Ann
gels to fat grafts obtained by liposuction enhances the Thor Surg 1992;53:530–531
fat’s longevity when injected for contour augmenta- 13. Welsh WJ. Autologous platelet gel—clinical function and
tion.17 When platelet gel is used in conjunction with su- usage in plastic surgery. Cosmet Dermatol 2000;13:13–39
tures it provides for greater tensile strength of irradiated 14. Gottumukkala VN, Sharma SK, Philip J. Assessing platelet
bowel anastomoses compared with sutures alone.16 Fi- and fibrinogen contribution to clot strength using modified
brin glue has also been used with improved outcomes in thromboelastography in pregnant women. Anesth Analges
reduction mammoplasties, abdominoplasties, mastec- 1999;89:1453–1455
15. Whitman DH, Berry RL. A technique for improving the
tomies, and axillary node dissections.16 handling of particulate cancellous marrow grafts using plate-
let gel. J Oral Maxillofac Surg 1998;56:1217–1218
16. Steed DL. The role of growth factors in wound healing. Surg
Clin North Am 1997;77:575–586
SUMMARY 17. Man D, Plosker H, Winland-Brown JE. The use of autolo-
Platelet gels represent the most recent of the line of tis- gous platelet-rich plasma (platelet gel) and autologous plate-
sue adhesives that combine the advantages of fibrin glue let-poor plasma (fibrin glue) in cosmetic surgery. Plast Re-
constr Surg 2001;107:229–237
with the additional benefits of PDGFs and cytokines.
18. Kevy S, Jacobson, M. Children’s Hospital, Center for Blood
Furthermore, a safe autologous form of the product is Research Laboratories: Harvard Medical School; 2000
readily available at the point of use in the operating room 19. Adler SC. Autologous platelet gel with growth factors in fa-
with minimal cost and effort. This, coupled with the cial plastic surgery. (Personal communication)
myriad of uses exemplified by this report, suggests that 20. Bruck HG. Fibrin tissue adhesion and its use in rhytidec-
this technology is likely to see even broader applicability. tomy: a pilot study. Aesth Plast Surg 1982;6:197–202
However, because platelet gels are an emerging 21. Marchac D, Sandor G. Face lifts and sprayed fibrin glue: an
outcome analysis of 200 patients. Br J Plast Surg 1994;47:
technology much of the present literature is anecdotal.
306–309
As this technology becomes more mainstream, larger 22. Mommaerts MY, Beirne JC, Jacobs WI, Abeloos JS, De
studies will become available to quantify the benefits Clercq CA, Neyt LF. Use of fibrin glue in lower blepharoplas-
and clarify the optimal application for this product. ties. J Cranio-Maxillo-Fac Surg 1996;24:78–82
23. Matras H. Fibrin seal: the state of the art. J Oral Maxillofac
Surg 1985;43:605–611
24. Tayapongsak P, O’Brien DA, Monteiro CB, Arceo-Diaz LY.
REFERENCES Autologous fibrin adhesive in mandibular reconstruction with
particulate cancellous bone and marrow. J Oral Maxillofac
1. Quinn J, Wells G, Sutcliffe T, et al. A randomized trial com- Surg 1994;52:161–165; discussion 166
paring octylcyanoacrylate tissue adhesive and sutures in the 25. Davis BR, Sandor GK. Use of fibrin glue in maxillofacial sur-
management of lacerations. JAMA 1997;277:1527–1530 gery. J Otolaryngol 1998;27:107–112.

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