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Adhesive Use in Oral

and Maxillofacial
Surgery
Michael J. Buckley, DMD, MBA, MSa,b,*,
Eric J. Beckman, PhDc,d
KEYWORDS
Tissue adhesives  Adhesives for bone fixation
Cyanoacrylates  Fibrin sealants
Collagen-based sealants
Synthetic polymer-based materials
Protein-based sealants

The tissue adhesive market is a vibrant and


dynamic sector with emerging technologies and
innovative concepts for cutting-edge applications.
Presently in oral and maxillofacial surgery, adhesives have a minimal role, but this is changing
rapidly. In oral and maxillofacial surgery, closure
of soft tissue wounds is primarily done with
mechanical devices, such as sutures and staples.
To close larger soft tissue wounds or develop large
soft tissue flaps in cosmetic and reconstructive
procedures, clinicians use mechanical devices
and apply drains that help evacuate dead spaces
to prevent hematomas and seromas. Similarly
bone fixation in oral and maxillofacial surgery is
primarily done with external fixation, such as maxillomandibular fixation, or with internal fixation
using small bone plates and screws. The emerging
adhesives and sealants are likely to have clinical
applicability in oral and maxillofacial surgery
soon and accelerate this clinical change.

IDEAL PROPERTIES OF TISSUE ADHESIVES


The ideal tissue adhesive must be biodegradable
and biocompatible. To be effective, it must have
both significant cohesive (covalent bonding of
glue molecules to each other) and adhesive
(bonding of glue molecules to adjacent tissue)
properties. To be biocompatible, tissue adhesives

must pass both acute and subacute toxicity tests


and have minimal cytotoxicity. The adhesive
must have a suitable setting time and be user
friendly, requiring little preparation time. It should
also have no special storage or shipping requirements. It must be relatively hydrophilic so it readily
spreads on wet surfaces at body temperature, and
have adequate working time for the given application. The adhesives must be strong, yet flexible,
with an elastic modulus similar to that of the tissue
being glued. Lastly, the adhesives must have
minimal heat generation (exothermic) characteristics and degrade with minimal inflammatory
response. At the moment, no adhesives on the
market fulfill all of these requirements.
Surgeons have been using tissue sealants and
adhesives since the early nineteenth century.1
There are presently four types of tissue adhesives:
fibrin sealants, collagen-based sealants, synthetic
polymer-based materials, and protein-based sealants. In 2000, fibrin sealants accounted for 86% of
the total tissue sealant market while protein-based
sealants accounted for 12% and synthetic polymer-based materials represented 2%.2

FIBRIN ADHESIVES
In the early 1940s, the combination of fibrin and
thrombin was first used as an adhesive. These

Private Practice, 31 N Maple Avenue, Greensburg, PA 15601, USA


University of Pittsburgh School of Dental Medicine, 3501 Terrace Street, Pittsburgh, PA 15213, USA
c
Cohera Medical Inc, Pittsburgh, PA, USA
d
University of Pittsburgh School of Engineering, 3800 OHara Street, Pittsburgh, PA 15213, USA
* Corresponding author. Private Practice, 31 N Maple Avenue, Greensburg, PA 15601.
E-mail address: mbuckley@coheramed.com
b

Oral Maxillofacial Surg Clin N Am 22 (2010) 195199


doi:10.1016/j.coms.2009.10.008
1042-3699/10/$ see front matter 2010 Elsevier Inc. All rights reserved.

oralmaxsurgery.theclinics.com







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Buckley & Beckman


fibrin sealants and glues were developed and used
extensively in the 1960s with donor-preserved and
autologous-donated plasma as the source of the
coagulation components. In 1977, however, the
US Food and Drug Administration (FDA) revoked
the license for the commercial use of fibrin sealants and glues from donor-preserved human
plasma because of the possibility of disease transmission.35 The fibrin glues presently on the
market are Tisseel (Baxter International Inc, Deerfield, Illinois) and Hemaseel (Haemacure Corp,
Montreal, Canada). The fibrin glues in head and
neck surgery are primarily used as hemostatic
agents over large surface areas and are very effective for that use. Fibrin glues, however, require
mixing of several different components on the
back table, which takes 20 to 40 minutes, before
they can be used. Fibrin glues are good hemostatic agents but are poor adhesives as they
exhibit a very weak bond. They are, however,
entirely biodegradable and biocompatible.6

COLLAGEN- AND PROTEIN-BASED SEALANTS


Collagen- and protein-based adhesives and sealants are made up of connective tissue components used as a two-part adhesive by taking
advantage of the ability of the components to
cross-link upon mixing. Collagen, when crosslinked with glutaraldehyde, forms a protein-based
sealant that can seal against both air and fluid
leakage. This two-part sealant also creates
a weak adhesive bond to adjacent tissue and is
sometimes referred to as an adhesive for that
reason. Protein-based adhesives (eg, BioGlue
[CryoLife, Kennesaw, Georgia]) have several
disadvantages: Because they are made from
bovine serum albumin, they pose a small risk for
transmission of disease and contain a foreign
protein that can cause hypersensitization.7 More
importantly, they use glutaraldehyde as the
cross-bonding agent, which is a neurotoxin.
Degradation of these sealants is very slow and
strong inflammatory responses can result.
Because of their weak adhesive strength, their
use in craniomaxillofacial surgery is primarily in
free flap surgery as a sealant around a vascular
anastamosis.8,9
Another of the two-part sealants, is DuraSeal
(Confluent Surgical, Inc, Waltham, Massachusetts), an FDA-approved product for use in dural
sealing. When employed for appropriate dural
closure, DuraSeal can be used to complete the
watertight closure necessary in this tissue. DuraSeal is a polyethylene glycolbased hydrogel that
is synthetic, absorbable, and easily applied. It is
designed such that each of its two parts contains

polyethylene glycol polymers with complementary


functional groups at the polymer chain ends. When
mixed, these complementary groups react with
each other, leading to a rapid cure. Its use as an
adhesive, however, is limited because of its poor
adhesive strength. DuraSeal is readily degradable
(the linkages formed during curing are hydrolytically cleaved) and biocompatible.10

CYANOACRYLATES
Cyanoacrylates (superglues) have been used for
years as wound-closure materials. Octyl-cyanoacrylates and butyl-cyanoacrylates have been
recently used as skin-closure adhesives with
good success. All of the cyanoacrylates operate
as adhesives in similar manners. They are applied
as mononers, which then rapidly polymerize to
a high molecular-weight material.1113 The presence of the cyano group on the acrylate monomer
enables initiation of polymerization (curing) simply
by water or amine groups present on proteins,
a characteristic not present in typical acrylates.
Conventional superglue (methyl cyanoacrylate)
cures to a hard, brittle material, whereas the octyl
and butyl analogs used as tissue adhesives form
a more resilient material once cured. While exhibiting a strong adhesive bond once cured, cyanoacrylates do not biodegrade to any real extent and
can induce a significant inflammatory response
given their hydrophobic nature. Their use has
generally been limited to superficial wounds.
Cyanoacrylate tissue adhesives form a strong
bond across tissue-wound edges, enabling
normal healing to occur below the seal. They are
marketed to replace small sutures in incision and
laceration repairs. These adhesives have been
shown to save time and provide a flexible waterresistant protective coating that will seal head
and neck wounds from water exposure and
contamination. They can be used safely in small
wounds, but also in larger wounds where subcutaneous sutures are needed and a watertight sealant
is appropriate. There is a small exothermic reaction during curing, but the patient does not usually
feel the temperature rise. These cyanoacrylates
have been shown to have some antimicrobial
properties.14

POLYURETHANE ADHESIVES
Polyurethane adhesives exhibit a wide range of
physical and mechanical properties that make
them attractive candidates for biomedical use.
Created by the reaction of polyester- or polyether-polyols with polyfunctional isocyanates,
polyurethane polymers are frequently used in

Adhesive Use in Oral and Maxillofacial Surgery

O=C=N-CH2-CH2-CH2-CH2-CH-COO-C2H5
N=C=O

H
HO-CH2-C-CH2-OH

(3) Lysine di-isocyanate (LDI)

OH
(1) Glycerol

N=C=O
H
O=C-N-CH2-CH2-CH2-CH2-CH-COO-C2H5
O=

H
O-CH2-C-CH2-O-C-N-CH2-CH2-CH2-CH2-CH-COO-C2H5
H
N=C=O
O
O=C-N-CH2-CH2-CH2-CH2-CH-COO-C2H5
H
N=C=O

Fig. 1. Reaction of glycerol and lysine di-isocyanate (LDI). LDI is composed of a lysine core (black) with two isocyanate groups (blue). One glycerol (red) reacts with three LDI molecules to produce an isocyanate-capped glycerol
prepolymer. The reaction of the hydroxyl groups on glycerol with the isocyanate groups on LDI produces
a urethane linkage (green). The resultant prepolymer has three unreacted isocyanate groups remaining.

medical applications, such as heart valves, dialysis


membranes, breast implants, and aortic grafts.
When employed as an adhesive, a urethane prepolymer generally has an oligomeric (rather than polymeric) structure and contains terminal (ie, at chain
ends) isocyanate groups (Fig. 1). These groups
react readily with hydroxyls and amines found in
tissue, forming a strong bond with the surface. In
addition, the presence of water leads to rapid
curing through the transformation of some of the
isocyanate groups to amines, followed by reaction
of these amines with nearby isocyanates to create
urea crosslinks. Although various adhesive and
nonadhesive biodegradable polyurethanes have
been synthesized, current available synthetic
adhesive components have met with limited
commercial success for a number of reasons. For
example, a number of such compositions exhibit
unacceptable toxicity arising, for example, from
the cytotoxicity of the degradation products of
the isocyanates used in the synthesis of these
adhesives. Isocyanates are generated from the
analogous amines, and several of the aromatic
amines used to create commercial isocyanates
(those used in foam bedding and seating) have
been shown to be carcinogenic, rendering such
isocyanates entirely unsuitable for use in medical
adhesives. In addition, early attempts at using
commercial polyisocyanates and polyols in
medical adhesives led to cured products that
were too hydrophobic to degrade quickly.
Recently in development and beginning initial
clinical trials is a lysine-derived urethane tissue
adhesive that may prove ideal for fixation of deep
wounds. This adhesive is biocompatible, resorbable, and nontoxic and could dramatically improve
the field of wound closure and hence significantly
advance surgical care. This adhesive is best

used on plainer tissues and will be suitable for


reducing or eliminating dead space in large traumatic wounds and for developing soft tissue flaps.
Its use in eliminating dead space and preventing
seromas and hematomas in cosmetic surgery
procedures, such as in face lifts and forehead lifts,
will likely be significant. In a recent study using
a canine abdominoplasty model (Fig. 2), use of
the lysine-based urethane adhesive decreased

Fig. 2. Comparison of test lysine di-isocyanate adhesive and control in canine abdominoplasty model.
(From Gilbert TW, Badylak SF, Gusenoff J, et al. Lysinederived urethane surgical adhesive prevents seroma
formation in a canine abdominoplasty model. Plast
Reconstr Surg 2008;122:95102; with permission.)

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Buckley & Beckman

198

Failure Strength (N/cm^2)

Control
Glue
Strain
Strain
(N/cm^2) SD
(N/cm^2) SD
Time
1 hours
0.268
0.213
10.437
12 hours
0.612
0.185
3.883
24 hours
0.992
0.13
8.358
1 week
3.2
1.869
14.472
2 weeks
19.861
11.553
22.789
4 weeks
62.866
22
56.571

to hold bony fragments in their original anatomic


position and enable osseous union between these
fragments would be of great benefit. Presently,
a polyurethane adhesive with building blocks has
been designed to give significant bony strength,
and still allow for osseous union to occur.1516

5.451
0.937
6.315
4.414
14.912
19.8

70
60

SUMMARY

50
40
Control
Glue

30
20
10
0
1 hours 12 hours 24 hours 1 week

Time

2 weeks 4 weeks

Fig. 3. Strength comparison of TissuGlue (Cohera


Medical, Inc, Pittsburgh, Pennsylvania). Tensile
strengths were measured for control wounds and
wounds with TissuGlue at 1 hour, 12 hours, 24 hours,
and 1 week. At all time points, tensile strength of
wounds with TissuGlue were stronger than that of
a naturally healing wound at 1 week.

wound exudates by 97%, versus the control, with


minimal inflammatory response. As shown in
Fig. 3, tensile strengths were measured for control
wounds and wounds with a polyurethane adhesive
at 1 hour, 12 hours, 24 hours, and 1 week. At all
time points, tensile strengths of the polyurethane-closed wounds were stronger than that of
a naturally healing wound at 1 week. Histologic
analysis revealed no tissue reaction, minimal
inflammation, and no necrosis of muscle-wound
tissue. Planar wounds in the head and neck region
could greatly benefit from an adhesive with the
chemical proprieties and surgical strength to eliminate the dead space.
The various building blocks of the polyurethane
adhesives can be blended in different proportions
to create adhesives with a useful range of physical
properties and cure times. Polyurethane created
via moisture curing of the prepolymer simply
degrades to an initial hydroxyl-containing
compound plus lysine, small amounts of ethanol,
and carbon dioxide.

BONE ADHESIVE
A particular problem in oral and maxillofacial
surgery is bone fixation of small pieces of bone
where use of bone screws and bone plates is
impossible or impractical. These applications might
include not only small fragments of bone in the craniomaxillofacial region, but also fixation of intracapsular fractures where the use of screws and bone
plates is precluded. A bone adhesive strong enough

Presently, tissue adhesives and sealants have


a limited use in oral and maxillofacial surgical
procedures.17 Skin closure occurs regularly with
cyanoacrylate adhesives.1823 Sealing of dural
tears in conjunction with dural closure has been
shown to be very successful. With the development of more head and neck reconstructive procedures and cosmetic procedures, demand will
increase for better surgical adhesives. Clinical
trials are beginning for newly developed adhesives
with the chemical characteristics, the safe reabsorptive profile, and the adhesive strength necessary to benefit oral and maxillofacial surgery
patients in the near future. Adhesives for bone fixation, while in early development, also show a promising chemical profile and will be of significant
benefit to oral and maxillofacial surgical patients.

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