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Degenerative Disorders of the Temporomandibular Joint: Etiology, Diagnosis, and Treatment

E. Tanaka, M.S. Detamore and L.G. Mercuri
J DENT RES 2008 87: 296
DOI: 10.1177/154405910808700406

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 CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE
Degenerative Disorders of the Temporomandibular Joint:
Etiology, Diagnosis, and Treatment
E. Tanaka1*, M.S. Detamore2, and L.G. Mercuri3
1 Department of Orthodontics and Dentofacial Orthopedics, The
University of Tokushima Graduate School of Oral Sciences, 3-18-15
Kuramoto-cho, Tokushima 770-8504, Japan; 2 Department of
Chemical and Petroleum Engineering, University of Kansas,
Lawrence, KS, USA; and 3Department of Surgery, Division of Oral
and Maxillofacial Surgery, Stritch School of Medicine, Loyola
University Medical Center, Maywood, IL, USA; *corresponding
author, etanaka@hiroshima-u.ac.jp
J Dent Res 87(4):296-307, 2008
ABSTRACT
Temporomandibular joint (TMJ) disorders have complex
and sometimes controversial etiologies. Also, under
similar circumstances, one person's TMJ may appear to
deteriorate, while another's does not. However, once
degenerative changes start in the TMJ, this pathology can
be crippling, leading to a variety of morphological and
functional deformities. Primarily, TMJ disorders have a
non-inflammatory origin. The pathological process is
characterized by deterioration and abrasion of articular
cartilage and local thickening. These changes are
accompanied by the superimposition of secondary
inflammatory changes. Therefore, appreciating the
pathophysiology of the TMJ degenerative disorders is
important to an understanding of the etiology, diagnosis,
and treatment of internal derangement and osteoarthrosis
of the TMJ. The degenerative changes in the TMJ are
believed to result from dysfunctional remodeling, due to a
decreased host-adaptive capacity of the articulating
surfaces and/or functional overloading of the joint that
exceeds the normal adaptive capacity. This paper reviews
etiologies that involve biomechanical and biochemical
factors associated with functional overloading of the joint
and the clinical, radiographic, and biochemical findings
important in the diagnosis of TMJ-osteoarthrosis. In
addition, non-invasive and invasive modalities utilized in
TMJ-osteoarthrosis management, and the possibility of
tissue engineering, are discussed.
KEY WORDS: temporomandibular joint, degenerative
disease, osteoarthrosis, tissue engineering.
Received April 17, 2007; Last revision January 21, 2008; Accepted
January 23, 2008
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International and American Associations for Dental Research
INTRODUCTION
I1980,
n humans, the temporomandibular joint (TMJ) is now generally
considered to be load-bearing during masticatory function. Until
however, this concept was controversial. Wilson (1920)
reported that the fibrocartilage of the TMJ condyle was softer than
hyaline cartilage, and therefore could not be load-bearing. Hylander
and Bays (1979) indirectly measured TMJ condylar loading in the
macaque with rosette strain gauges placed on the condylar neck,
and found that the condylar bone surface was indeed loaded during
function. Brehnan et al. (1981) and Boyd et al. (1990) directly
measured the condylar loading in the macaque by means of a
piezoelectric foil force transducer, and confirmed that the TMJ was
indeed a load-bearing articulation. Other experimental and
analytical studies (Smith et al., 1986; Koolstra et al., 1988; Korioth
et al., 1992; Beek et al., 2000) have also demonstrated that the
human TMJ was load-bearing under function. Although these
studies are all simulations, partially performed on data from
cadavers, they have shown that the fibrocartilaginous tissues,
including the disc and articular cartilage, have important functions
in stress distribution.
TMJ disorders are characterized by intra-articular positional
and/or structural abnormalities. Review studies published in the
1980s showed prevalence rates ranging from 16% to 59% for
symptoms and from 33% to 86% for clinical signs (Carlsson and
LeResche, 1995), although from 3% to 7% of the adult population
has sought care for TMJ pain and dysfunction (Carlsson, 1999). It
has been observed that up to 70% of persons with TMJ disorders
suffer from displacement of the articular disc, coined 'internal
derangement' of the TMJ (Farrar and McCarty, 1979).
Meanwhile, the most common joint pathology affecting the
TMJ is degenerative joint disease, also known as osteoarthrosis or
osteoarthritis. Among individuals with TMJ disorders, 11% had
symptoms of TMJ-osteoarthrosis (TMJ-OA) (Mejersjö and
Hollender, 1984). An epidemiological study, meanwhile, showed
that minimal flattening of the condyle and/or eminence was seen in
35% of TMJs in asymptomatic persons (Brooks et al., 1992). More
advanced osseous changes were not seen; therefore, it was
concluded that minimal flattening was probably of no clinical
significance. However, once the breakdown in the joint starts, TMJ-
OA can be crippling, leading to a variety of morphological and
functional deformities (Zarb and Carlsson, 1999).
This paper is divided into four parts. Part 1 will review the
definition and etiology of TMJ disorders. A basic review of the
TMJ disorders, their etiologies, and the biomechanical and
biochemical factors associated with functional overloading of the
joint will also be discussed. Part 2 will discuss the clinical,
radiographic, and biochemical analytical findings important in the
diagnosis of TMJ-osteoarthrosis. Part 3 will present the non-
invasive and invasive modalities utilized in TMJ-osteoarthrosis
management. Finally, in Part 4, the possibility of tissue-engineering
for treatment of TMJ disorders with degenerative changes will be
discussed.
J Dent Res 87(4) 2008 Degenerative Disorders of the TMJ 297

DEFINITION AND
ETIOLOGY OF TMJ
DISORDERS
Classification of TMJ
Degenerative Disorders
Unlike rheumatoid arthritis, TMJ-
osteoarthrosis has a non-inflam-
matory origin. The pathological
process is characterized by
deterioration and abrasion of
articular cartilage and local
thickening and remodeling of the
underlying bone (Zarb and
Carlsson, 1999). These changes
are frequently accompanied by the
superimposition of secondary
inflammatory changes. Therefore,
mechanically induced osteo -
arthrosis may better reflect TMJ-
osteoarthrosis.
Internal derangement of the
TMJ is defined as an abnormal
positional relationship of the disc
relative to the mandibular condyle
and the articular eminence (Fig.
1). Wilkes (1989) established 5 Figure 1. Magnetic resonance images of TMJ-internal derangement and -osteoarthrosis. Internal
stages based on clinical and derangement of the TMJ is defined as an abnormal positional relationship of the disc relative to the
imaging criteria. In Stage I, mandibular condyle and the articular eminence, while TMJ-osteoarthrosis is characterized by structural
failure of articular cartilage in the early stage and by the deterioration of the cartilage and subchondral
clinical observations include bone, resulting in shortening of the mandibular ramus and subsequent mandibular retrusion. Both internal
painless clicking and unrestricted derangement and osteoarthrosis of the TMJ are regarded as a frequent cause of pain and/or disturbed
mandibular motion. When imaged, mandibular movement. The characteristic radiographic sign of TMJ-osteoarthrosis is dysfunctional
the disc is displaced slightly remodeling on the mandibular condyle and articular eminence surfaces with osteophyte formation. (A) At
forward on opening, although it is the initial stage, the disc reveals a slight anterior disc displacement but not complete displacement at the
intercuspal position. At maximum mouth opening, the disc is located between the condylar and temporal
reduced at the maximum mouth bone surfaces, and the condyle and disc move harmoniously. Arrowheads indicate the anterior and
opening ('reducing' refers to the posterior ends of the disc. (B) At the intercuspal position, the disc reveals anterior displacement, but not
disc sliding back to a "normal" bony remodeling and deformation. On full opening, the disc reduces, usually resulting in 2 noises
anatomical position during mouth (reciprocal clicking). Arrowheads indicate the anterior and posterior ends of the disc. (C) Through
mandibular movements, the disc is displaced from its normal position, and on full opening, the disc
opening, producing the audible deformity occurs because the condyles push the disc forward and downward. In this case, bony changes
clicking sound), and the osseous on the condylar surface are not detected. Arrowheads indicate the anterior and posterior ends of the disc.
contours appear normal (Fig. 1A). (D) The disc also reveals anterior displacement without reduction, in which the disc is severely deformed on
In Stage II, there are complaints of full opening. Arrowheads indicate the anterior and posterior ends of the disc. Furthermore, the osteophyte
occasional painful clicking, of the peripheral cortical bone, indicated by arrows, is clearly detected, indicating TMJ-osteoarthrosis. (E)
The condyle shows severe bony deformation with flattening and erosion, indicating severe osteoarthrosis of
intermittent locking, and the TMJ. Arrows indicate the deformed surface of the mandibular condyle. The disc also reveals anterior
headaches. When imaged, the disc displacement without reduction. Arrowheads indicate the anterior and posterior ends of the disc. The
appears slightly deformed and individual at this stage is likely to have spontaneous joint pain and movement disability.
displaced slightly forward at
maximum opening, but still
reduces at maximum opening (Fig.
1B). The osseous contours appear normal. In Stage III, displaced (YJ Chen et al., 2000, 2002). A series of
clinically, there is frequent joint pain and tenderness, experimental studies with surgical induction of anterior disc
headaches, locking, and restricted range of mandibular motion, displacement in the rabbit showed that disc displacement led to
as well as painful chewing. When imaged, anterior disc the degenerative changes in the condylar cartilage (Sharawy et
displacement is seen, with moderate thickening (Fig. 1C). This al., 2000, 2003). In contrast, the apparent radiographic
disc reduces early in Stage III, but progresses to non-reducing association of articular degeneration with disc displacement has
(i.e., locking) on opening in the later stage. The bony contours led to the suggestion that the degenerative process may be a
remain normal in appearance. At the maximum mouth opening, predisposing factor for disc displacement (Dijkgraaf et al.,
the disc is subjected to deformity, because the condyle pushes 1995). However, cadaver (Rohlin et al., 1985), clinical
the disc forward and downward (Fig. 1C). Recent studies, using (Westesson et al., 1989), and magnetic resonance imaging
individual oblique-axial magnetic resonance imaging, have studies (Kircos et al., 1987) have demonstrated that disc
shown that most anteriorly displaced discs were laterally displacement is a common finding in asymptomatic

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International and American Associations for Dental Research

298
individuals. In Stage IV, individuals complain of chronic pain,
headache, and restricted mandibular range of motion. When
imaged, a markedly thickened disc is anteriorly displaced and
does not reduce on opening, and abnormal contours to both the
condyle and articular eminence begin to become evident (Fig.
1D). In Stage V, clinically, individuals experience pain,
crepitus, and pain with mandibular function. When imaged, the
now grossly deformed disc is anteriorly displaced, without
reduction, and degenerative changes are present in the osseous
components of the articulation (Fig. 1E). The disease process is
characterized by deterioration and abrasion of articular
cartilage and disc surfaces, and occurrence of thickening and
remodeling of the underlying bone. Therefore, osteoarthrosis
may be a final common pathway for several joint conditions,
including inflammatory, endocrine, metabolic, developmental,
and biomechanical disorders (Zarb and Carlsson, 1999).
Etiology of TMJ Degenerative Disorders
Increased loading in the TMJ may stimulate remodeling,
involving increased synthesis of extracellular matrices
(Stegenga et al., 1989). Remodeling is an essential biological
response to normal functional demands, ensuring homeostasis
of joint form, and function and occlusal relationships (Smartt et
al., 2005). Arnett et al. (1996a,b) proposed an explanation for
the pathophysiology of the degenerative changes as one that
results from dysfunctional articular remodeling due to (1) a
decreased adaptive capacity of the articulating structures of the
joint or (2) excessive or sustained physical stress to the TMJ
articular structures that exceeds the normal adaptive capacity.
The former is the host-adaptive capacity factor, which is
associated with the host's general condition. Advancing age,
systemic illness, and hormonal factors may define the host-
adaptive capacity of the TMJ. This factor may contribute to
dysfunctional remodeling of the TMJ, even when the
biomechanical stresses are within a normal physiologic range.
Age is clearly a predisposing factor, because both frequency
and severity of the disease appear to increase with aging. For
example, the calcium content of the human disc increases
progressively with aging (Takano et al., 1999). This increase in
calcification may be caused by aging as such, or by a changed
mechanical stress (Jibiki et al., 1999). Accordingly, the
material properties of the disc can also be expected to be
related to age (Tanaka et al., 2001). This implies that the disc
becomes more stiff and fragile in nature, reducing its capability
to handle overload. Articular cartilages can also change with
aging. The molecular weight of hyaluronic acid in human
articular cartilage decreases from 2000 to 300 kDa between the
ages of 2.5 and 86 yrs (Holmes et al., 1988). Hyaluronic acid in
articular cartilage is essential for it to maintain its viscosity, and
any decrease in molecular weight can lead to reduction of its
biorheological property in cartilage.
Systemic illness may also influence fibrocartilage
metabolism and could affect the adaptive capacity of the TMJ.
These illnesses may include autoimmune disorders, endocrine
disorders, nutritional disorders, metabolic diseases, and
infectious disease. Hormonal factors may also have a marked
influence on remodeling of the mandibular condyle. In these
cases, the TMJ degenerative disorders may be the result of
systemic disease.
Mechanical factors can also cause changes in the TMJ
structure. Despite host-adaptive capacity, excessive or
unbalanced mechanical loading in the TMJ can cause overload
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Tanaka et al. J Dent Res 87(4) 2008
of articular tissues, resulting in the onset and progression of
TMJ-osteoarthrosis. Furthermore, internal derangement of the
TMJ may be induced by excessive or unbalanced stress in the
TMJ. From a review of etiological mechanical events of TMJ-
internal derangement and -osteoarthrosis, trauma,
parafunction, unstable occlusion, functional overloading,
and increased joint friction play a role (Stegenga et al., 1989;
Arnett et al., 1996a,b; Nitzan, 2001). These factors may occur
alone or may be interrelated, interdependent, and/or co-
existent.
Macrotrauma in the condylar area can cause degeneration
of the articular cartilage and production of inflammatory and
pain mediators. Trauma has been reported to alter the
mechanical properties of the disc (Nickel et al., 2001) and to
cause mechanical fatigue of the disc (Beatty et al., 2001, 2003).
Furthermore, it may cause cartilage degradation and production
of inflammatory and pain mediators. TMJ alterations occurred
over time after the macrotrauma, leading to progressive
condylar resorption and deformation (Arnett et al., 1996b).
However, only about one-third of the individuals with TMJ
degenerative changes reportedly suffered previous trauma to
the head and neck (Laskin, 1994). The mechanism of delayed
condylar resorption and deformation in secondary macrotrauma
is not understood, but the clinician should recognize the
etiologic importance of the macrotrauma and long-term
evaluation of the TMJ form and function after macrotrauma.
Parafunction may produce abnormal compression and
shear forces capable of initiating disc displacement and
condylar and articular eminence degenerative changes (Gallo et
al., 2006). Parafunctional hyperactivity of the lateral pterygoid
muscle has been considered to lead to masticatory muscle pain
(Hiraba et al., 2000; Murray et al., 2001). Since the superior
head of the lateral pterygoid muscle attaches partly to the
articular capsule of the TMJ and directly or indirectly to its
articular disc (Murray et al., 2001), it has been hypothesized
that dysfunction of this muscle can lead to TMJ-internal
derangement and -osteoarthrosis (Hiraba et al., 2000).
Functional overloading and increased joint friction may
act together as etiological events for TMJ-internal derangement
and -osteoarthrosis. Growing evidence suggests that functional
overload with subsequent microtrauma is a crucial event for
TMJ-internal derangement and -osteoarthrosis. Milam et al.
(1998) proposed the direct mechanical injury and
hypoxia/reperfusion injury model, suggesting that the oxidative
stress results in the accumulation of free radicals that damage
the articular tissues of the TMJ. Several studies have
demonstrated the presence of reactive oxidative radical species
in synovial fluid from diseased TMJs (Kawai et al., 2000;
Takahashi et al., 2003).
Mechanism of Functional Overloading
for TMJ Degenerative Disorders (Fig. 2)
In chondrocytes of articular cartilage, cyclic tensile loading up-
regulated the expression of matrix metalloproteinase (MMP)-
13 and vascular endothelial growth factor (VEGF) and down-
regulated the expression of tissue inhibitor of matrix
metalloproteinases (TIMP)-1, while cyclic hydrostatic pressure
induced opposite effects (Wong et al., 2003). VEGF expression
in osteoarthritic cartilage appeared to increase progressively
with the applied mechanical overload. Furthermore, VEGF
induction in chondrocytes by mechanical overload has been
linked to activation of hypoxia-induced transcription factor-1
J Dent Res 87(4) 2008 Degenerative Disorders of the TMJ 299

(Forsythe et al., 1996). Recently,

Tanaka et al. (2005a) showed that
mandibular condylar cartilage in
mechanically induced TMJ-
osteoarthrosis expressed abundant
VEGF. VEGF regulates the production
of MMPs and TIMPs, which are
among the effectors of extracellular
matrix remodeling (Pufe et al., 2004).
Reduction of TIMPs and induction of
MMPs result in an imbalance in the
turnover of extracellular matrix
components, collagens, and
proteoglycans, which are degraded
more rapidly than they are formed.
The loss of balance toward increased
extracellular matrix degradation
results in the destruction of cartilage
(Pufe et al., 2004).
The expression of VEGF is also
up-regulated in the synovial tissues
(Sato et al., 2003) and the TMJ disc
(Leonardi et al., 2003) in TMJ-internal Figure 2. The concept of the process of cartilage breakdown in the TMJ. A decreased adaptive
derangement. This suggests that capacity of the articulating structures and/or excessive physical stress to the TMJ that exceeds the
normal adaptive capacity can induce dysfunctional remodeling. Functional overloading and
VEGF expression is involved in the increased joint friction may act together as etiological events for TMJ degenerative changes.
development of inflammatory changes Functional overloading can facilitate hypoxia in the TMJ and mediate the destructive processes
in the TMJ as a reaction to the associated with osteoarthrosis as an autocrine factor. Vascular endothelial growth factor (VEGF)
cytokine. The increased expression of induction in osteoarthritic cartilage by functional overloading is linked to activation of the hypoxia-
induced transcription factor-1, leading to hypoxia in the joint tissue. Furthermore, VEGF regulates
VEGF in the joint tissues might lead to
the production of matrix metalloproteinases and tissue-inhibitors of matrix metalloproteinases, which
an increase of VEGF in the synovial are among the effectors of extracellular matrix remodeling. Overloading also causes collapse of joint
fluid of persons with symptomatic lubrication as the result of the hyaluronic acid degradation by free radicals. The regulation of
TMJ-internal derangement (Sato et al., hyaluronic acid production is controlled by various pro-inflammatory cytokines. Of these cytokines,
2005). Consequently, mechanical tumor necrosis factor- ␣ and interleukin-1 and -6 play crucial roles in the pathogenesis of
osteoarthrosis with respect to the acceleration and progression of cartilage degradation, because
overload induces hypoxia-induced they promote bone resorption through the differentiation and activation of osteoclasts.
transcription factor-1, and the
subsequently generated VEGF
activates the chondrocytes in an
autocrine manner to produce MMPs and reduces TIMPs (Pufe 1991). Among other effects of reactive oxidative radical
et al., 2004). This implies that VEGF is probably induced in species in synovial joints are inhibition of the biosynthesis and
chondrocytes by mechanical overload, facilitating hypoxia and degradation of hyaluronic acid, both causing marked reduction
mediating the destructive processes associated with in viscosity of synovial fluid (Grootveld et al., 1991).
osteoarthrosis as an autocrine factor. In the healthy TMJ, the co-efficient of friction between the
Furthermore, in the condylar cartilage with TMJ- cartilage surfaces can be assumed to be almost zero by the
osteoarthrosis, the number of blood vessels and osteoclasts is presence of synovial fluid (Tanaka et al., 2004; Nickel et al.,
markedly increased in the area subjacent to the hypertrophic 2001, 2006). However, after an experimental abrasion of the
cell layer, where several VEGF-expressing chondrocytes are articular cartilage comparable with TMJ-osteoarthrosis, the co-
detected (Tanaka et al., 2005a). Since VEGF plays an efficient of friction was 3.5 times greater than that in the intact
important role not only in endothelial cell recruitment, but also joint (Tanaka et al., 2005b). As the coefficient of friction
in osteoclast recruitment (Niida et al., 1999), VEGF has increases, the shear stresses between the articular surfaces,
overlapping function in the support of osteoclastic bone within the disc, and articular cartilage become greater. Shear
resorption. Then, the increase in osteoclasts stimulated by stress can result in fatigue and damage and irreversibly deform
VEGF may induce destruction of cartilage, making vascular the TMJ tissues, initiating TMJ-internal derangement and -
invasion into the condylar cartilage easier. osteoarthrosis (Beatty et al., 2003; Tanaka et al., 2003).
Overloading also causes collapse of joint lubrication, as the Hyaluronan degradation is likely to occur in pathologic
result of hyaluronan degradation by free radicals (Nitzan, joints because of free-radical de-polymerization of the
2001). With overloading, the increase in intra-articular hyaluronic acid chain (McNeil et al., 1985) or the abnormal
pressure, when it exceeds the capillary perfusion pressure, will biosynthesis of hyaluronic acid by type B synovial cells
cause temporary hypoxia, which is corrected by re-oxygenation (Vuorio et al., 1982). Free radicals rapidly depolymerize
on cessation of degradation by the overloading. Such a hyaluronic acid in vitro, which may implicate them in the
hypoxia-reperfusion cycle has been reported to release reactive degradation of hyaluronic acid in vivo. Furthermore, the
oxidative radical species non-enzymatically (Grootveld et al., degradation of hyaluronic acid may lead to cartilage destruction

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300
Table 1. Classification of Arthritic Conditions Affecting the Joint.
Low-inflammatory Arthritic Disorders Degenerative joint disease (Osteoarthritis)
Post-traumatic arthritis
High-inflammatory Arthritic Disorders Infectious arthritis
Rheumatoid arthritic conditions
- adult and juvenile
Metabolic arthritic conditions
- gouty arthritis
- psoriatic arthritis
- lupus erythematosus
- ankylosing spondylitis
- Reiter’s Syndrome
- arthritis associated with ulcerative colitis
From Mercuri, 2006.
in terms of the enhanced expression of MMPs (Ohno-Nakahara
et al., 2004). Since neither healthy nor inflammatory synovial
fluids contain hyaluronidase activity, reactive oxidative radical
species are assumed to cause hyaluronic acid depolymerization
(McNeil et al., 1985). Considering the presence of reactive
oxidative radical species in synovial fluid from diseased TMJs
(Kawai et al., 2000), it is strongly suggested that reactive
oxidative radical species generated in diseased TMJs cause the
depolymerization of hyaluronic acid in synovial fluid.
The process of regulation of hyaluronic acid production is
also controlled by various cytokines, including interleukin-1␤,
tumor necrosis factor-␣, interferon-␥, and transforming growth
factor-␤. Tanimoto et al. (2004), using rabbit TMJ synovial
lining cells, demonstrated that TGF␤1 enhances the expression
of hyaluronic acid synthase-2 mRNA in the TMJ synovial
membrane fibroblasts and may contribute to the production of
high-molecular-weight hyaluronic acid in the joint fluid.
Several pro-inflammatory cytokines have been detected in the
synovial fluid obtained from persons with TMJ-internal
derangement and -osteoarthrosis (Kubota et al., 1998; Hamada
et al., 2006).
Of these cytokines, tumor necrosis factor-␣ and interleukin-
1 and -6, produced primarily by stimulated macrophages, play
crucial roles in the pathogenesis of rheumatoid arthritis and
osteoarthrosis, with respect to the acceleration and progression
of cartilage degradation, because they promote bone resorption
through the differentiation and activation of osteoclasts (Boyle
et al., 2003). A significantly high concentration of interleukin-6
was associated with severe synovitis, although interleukin-1␤
and interleukin-6 were detected even in asymptomatic TMJs
(Kubota et al., 1998). Interleukin-10 has also been suggested to
prevent and reverse cartilage degradation in rheumatoid
arthritis (van Roon et al., 1996). Recently, interleukin-10 was
detected even in synovial fluid obtained from persons with
TMJ-internal derangement (Hamada et al., 2006). These
findings suggested that cytokines in the synovial fluid might be
responsible for the progression and regulation of the
degenerative changes in the TMJ.
DIAGNOSIS
OF THE TMJ DEGENERATIVE DISORDERS
TMJ arthritic conditions can be classified as low-inflammatory
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International and American Associations for Dental Research
Tanaka et al. J Dent Res 87(4) 2008
or high-inflammatory types. Here, the term
"osteoarthritis" classically has been defined as a
low-inflammatory arthritic condition without pain,
either primary or secondary to trauma or other
acute and/or chronic overload situations,
characterized by erosion of articular cartilage,
which becomes soft, frayed, and thinned, resulting
in eburnation of subchondral bone and outgrowth
of marginal osteophytes. Meanwhile, the term
"osteoarthrosis", a synonym for "osteoarthritis" in
the medical orthopedic literature, has recently
come to be identified in the dental TMJ literature
with any non-inflammatory arthritic condition that
results in degenerative changes similar to those in
"osteoarthritis". However, in the dental TMJ
literature, "osteoarthrosis" has come to be
identified with the unsuccessful adaptation of the
TMJ to the mechanical forces placed on it with
disc derangement or disc interference disorders
(Stegenga et al., 1989). Since the basic etiology, pathology, and
management involved are the same, the terms "osteoarthritis"
and "osteoarthrosis" will be used synonymously.
Low-inflammatory arthritic conditions begin in the matrix
of the articular surface of the joint, with the subcondylar bone
and capsule secondarily involved (Table 1). The classic types
of low-inflammatory arthritis are (1) degenerative joint disease,
or primary osteoarthritis, produced by intrinsic degeneration of
articular cartilage, typically the result of age-related functional
loading, and (2) post-traumatic arthritis. Despite the fact that
these low-inflammatory arthritic conditions often involve the
TMJ, these conditions seldom require invasive surgical
intervention if they are managed appropriately in their early
stages. Individuals with the low-inflammatory type have low
leukocyte counts in the synovial fluid and laboratory findings
consistent with low-level inflammatory activity, and the
affected joint shows focal degeneration on imaging.
High-inflammatory arthritic conditions primarily involve
the synovial cells and joint bone (Table 1). The classic type of
high-inflammatory arthritis is rheumatoid arthritis. Other types
of high-inflammatory arthritic conditions include the metabolic
arthritic conditions, such as gout, arthritis of psoriasis, lupus
erythematosus, ankylosing spondylitis, infectious arthritis,
Reiter's Syndrome, and the arthritis associated with ulcerative
colitis. Although these disorders may be histologically and
chemically different, clinical findings and management are
often similar. In all instances, the TMJ can be involved, and
surgical intervention may be required to alleviate symptoms
and correct associated functional and esthetic problems.
Individuals with high-inflammatory-type arthritis have high
leukocyte counts in the synovial fluid and laboratory findings
consistent with high-inflammatory activity, and show a more
diffuse degeneration of the involved joints on imaging.
Signs and Symptoms of Arthritic Changes in the TMJ
The most common symptom of any arthritic TMJ condition is
painful joints. The pain arises from the soft tissues around the
affected joint and the masticatory muscles that are in protective
reflex spasm in accordance with Hilton's law. This orthopedic
principle states that the nerves that innervate a joint also
innervate the muscles that move that joint and the overlying
skin. This self-preservation physiologic reflex provides for the
protection of an injured or pathologically affected joint by
J Dent Res 87(4) 2008 Degenerative Disorders of the TMJ 301

causing the surrounding Table 2. Classification of Osteoarthrosis Based on Symptoms, Signs, and Imaging with Management Options.
musculature to contract
reflexively in response to Stage Symptoms Signs Imaging Management Options
intra-articular injury or
pathology, thus protecting it I Joint/muscle pain Little or no Mild to moderate Non-Invasive
from further damage. Pain Early Disease Limited function occlusal or facial erosive changes of or Minimally invasive
may also arise from the Crepitus esthetic changes condyle/fossa/eminence
subchondral bone that is
undergoing destruction as II Little or no joint pain Class II malocclusion Flattened Bone and Joint
the result of the arthritic Arrested Disease Muscle pain Apertognathia condyle/eminence Invasive or Salvage
process. Some joint dysfunction
Other common and Crepitus
significant signs and symp-
toms of TMJ arthritis are III Joint/muscle pain High-angle Class II Gross erosive changes Salvage
loss of joint function or late- Advanced Disease Loss of function malocclusion Loss of condyle and
stage ankylosis, joint +/-Crepitus Apertognathia eminence height
instability, and facial de - Progressive Developing Ankylosis
formity due to loss of retrognathia fibrosis/ankylosis Hypertrophy of coronoid
posterior mandibular verti-
cal dimension, as pathologic Modified from Steinbrocker et al., 1949, and Kent et al., 1986.
osteolysis decreases the
height of the condyle and
condyloid process, resulting in apertognathia (Mercuri, 2006). splint, medications, orthotics, and physical therapy. In the
clinic, the most common treatment of pain from the TMJ is by
Diagnosis occlusal splints. Occlusal splints are an effective device to
The diagnosis in late-stage arthritic TMJ disease is usually protect the TMJ from involuntary overloading, and to reduce
obvious, especially in the late-stage high-inflammatory arthritic the muscle hyperactivity and articular strain due to bruxism. In
diseases, when the disease process is manifest in other joints. a controlled study on the effects of occlusal splint therapy in
The problem in diagnosis comes with the uncommon individuals with severe TMJ-osteoarthrosis, a reduction of
individual whose arthritic disease first manifests itself as TMJ clinical signs was seen (Kuttila et al., 2002). However, critical
pain and mandibular dysfunction. A history of joint overload evaluation of splint therapy has not yet been conducted, due to
due to habits (e.g., excessive gum chewing, unilateral chewing) the lack of evidence, and their clinical effectiveness in relieving
or parafunction (e.g., bruxism, clenching) and clinical pain seems modest when compared with that of pain treatment
examination is important, but lacking any correlation between methods in general (Forssell and Kalso, 2004). None of the
the signs and symptoms, as well as the history and physical occlusal adjustment studies provided evidence supporting the
findings, the best approach to diagnosis may come in turning to use of this treatment method.
imaging and laboratory examination. In terms of medications, non-steroidal anti-inflammatory
agents, such as ibuprofen, should be used on a time-
MANAGEMENT OF THE TMJ contingent basis to take advantage of their pharmacokinetics.
DEGENERATIVE DISORDERS Muscle relaxants may be helpful in controlling the reflex
Principles for Management of TMJ-Osteoarthrosis masticatory muscle spasm/pain (Dionne, 2006). Oral
orthotics, while assisting in the control of parafunctional
Management of TMJ-osteoarthrosis may be divided into non-
habits in many persons, also can provide relief from
invasive, minimally invasive, and invasive or surgical
masticatory muscle spasm/pain and, along with a soft diet,
modalities. Finally, in end-stage disease, salvage modalities
will decrease the loads delivered across the TMJ articulation
must be considered. The decision for surgical management of
under function. Reconstruction of the occlusion to provide
TMJ-osteoarthrosis must be based on evaluation of the person's
bilateral occlusal stability, temporarily during the early stages
response to non-invasive management, the person's mandibular
of management, also will decrease the potential for unilateral
form and function, and the effect the condition has on the
joint overload (Clark, 1984). Physical therapeutic modalities
person's quality of life (Mercuri, 2006). The management goals
act as counter-irritants to reduce inflammation and pain.
in TMJ-osteoarthrosis should be: (1) decreasing joint pain,
Superficial warm and moist heat or localized cold may relieve
swelling, and reflex masticatory muscle spasm/pain; (2)
pain sufficiently to permit exercise. Therapeutic exercises are
increasing joint function; (3) preventing further joint damage;
designed to increase muscle strength, reduce joint
and (4) preventing disability and disease-related morbidity.
contractures, and maintain a functional range of motion.
Using a classification scheme based on clinical signs and
Ultrasound, electrogalvanic stimulation, and massage
symptoms and imaging, modified from that developed by
techniques are also helpful in reducing inflammation and pain
Steinbrocker et al. (1949) and Kent et al. (1986), we will
(De Laat et al., 2003).
present an evidence-based discussion for the management of
Active and passive jaw movements, manual therapy
TMJ-osteoarthrosis (Table 2).
techniques, and relaxation techniques were used in the
Non-invasive Management Modalities management of 20 consecutive persons with TMJ-
The non-invasive modalities of management include occlusal osteoarthrosis. After treatment (mean, 46 days), pain at rest was

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302
reduced in the 20 persons by 80%, and there was no functional
impairment in 37% of the 20 persons (seven persons)
(Nicolakis et al., 2001).
Minimally Invasive Modalities
Injections
Hyaluronic acid as an injectable, large, linear glycosamino-
glycan has been studied in other body joints. In double-blind
studies in other joints after 2 mos, hyaluronic acid has been
shown to provide significantly better results than saline. These
results were sustained for 1 yr. However, no significant
differences were noted in radiographic progression of the
disease (Lohmander et al., 1996).
An in vivo rabbit study reported that the hyaluronic-acid-
injected joints demonstrated limited cartilage change, less
fibrillation, and the presence of clusters of chondrocytes in the
deficit area, while the prednisolone-treated joint exhibited
worsening of the cartilage destruction (Shi et al., 2002). However,
to date, hyaluronic acid has not been approved by the United
States Food and Drug Administration as a safe and effective
medication in the management of arthritic disease in the TMJ.
Intra-articular injections of corticosteroids are of limited
use in other joints of the body (Gray and Gottlieb, 1983). The
main limitations of repeated intra-articular steroid injections are
the risks of infection and the destruction of articular cartilage.
Repeated intra-articular corticosteroid injections have been
implicated in the "chemical condylectomy" phenomenon in the
TMJ (Toller, 1977). Intra-articular injections of steroids should
be considered only in persons with evidence of acute high
inflammation of the joint. Multiple injections of steroids should
not be used. In all cases after intra-capsular injection of
steroids, decreased activities within pain-free limits should be
recommended, to prevent acceleration of the degenerative
process from over-activity and joint overload.
Arthrocentesis and Arthroscopy
Nitzan and Price (2001) presented a 20-month follow-up study
of 36 persons with 38 dysfunctional joints that had not
responded to non-surgical management, to determine the
efficacy of arthrocentesis in restoring functional capacity to the
osteoarthrosis joints. They concluded that arthrocentesis is a
rapid and safe procedure that may result in the TMJ-
osteoarthrosis returning to a functional state. Failure of
arthrocentesis (32%) suggested that painful limitation of TMJ
function might be the result of fibrous adhesions or osteophytes
that require arthrotomy for management.
The value of TMJ arthroscopy may be in the early
diagnosis and management of arthritic processes affecting the
TMJ, especially early-stage arthritic disease, to avoid the
complications of open bite and ankylosis (Holmlund et al.,
1986). Holmlund et al. (1986) described the arthroscopic
picture as varying widely, depending on when in the stages of
the arthritic process the procedure is performed and whether
disease-modifying therapeutic agents have been given. Late-
stage marked fibrosis or ankylosis makes arthroscopy
impossible and contraindicates its usefulness.
While the majority of persons with TMJ-osteoarthrosis can
be successfully managed with non-invasive/minimally invasive
procedures, there is a small percentage of persons with
osteoarthrosis (< 20%) who have such severe pathology, pain,
and dysfunction that invasive surgical management must be
considered (Mercuri, 2006). Since the later cases present such a
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Tanaka et al. J Dent Res 87(4) 2008
challenge for management and reconstruction, the authors
believe that, to complete the review of the topic, the invasive
surgical modalities must be discussed in some detail.
Invasive Surgical Modalities (Bone and Joint Procedures)
Arthroplasty
Reshaping the articular surfaces to eliminate osteophytes,
erosions, and irregularities found in osteoarthritis refractory to
other modalities of treatment was described by Dingman and
Grabb (1966). While this technique reportedly provided pain
relief, concerns about the resultant mandibular dysfunctions,
dental malocclusions, facial asymmetries, and the potential for
development of further bony articular degeneration, disc disorders
or loss, and ankylosis led to the development of techniques for
interposing autogenous tissues and alloplastic materials.
The need for replacement of the articular disc in such cases
remains controversial (Merrill, 1986). According to Moriconi et
al. (1986), TMJ replacement grafts should fulfill the following
criteria: biological compatibility, adequate strength, restoration
of biomechanical function, and resistance to the adverse affects
of the biological environment.
Autogenous Hemi-arthroplasty
Several different autogenous tissues have been advocated as a
replacement for the TMJ disc (Merrill, 1986); however, the
literature on the use of the vascularized local temporalis muscle
flap appears to present the most applicable data for the
management of the arthritic TMJ (Feinberg and Larsen, 1989).
Osteotomy
Individuals with active TMJ-osteoarthrosis and either
concomitant or resultant maxillofacial skeletal discrepancies,
and treated only with orthognathic surgery, often have poor
outcomes and significant relapse (Wolford et al., 1994, 2003).
Pre-existing TMJ pathology, with or without symptoms that can
lead to unfavorable orthognathic surgery outcomes, includes:
internal derangement, progressive condylar resorption,
osteoarthritis, condylar hyperplasia, osteochondroma, congenital
deformities, and non-salvageable joints (Wolford et al., 1994).
Since the TMJs are the foundation of orthognathic surgery,
the resultant pathology offers a poor base upon which to build
any maxillofacial functional skeletal reconstruction in conditions
where there are gross erosive changes in the articulating
components of both the fossa and condyle, resulting in loss of
vertical height. Further, the degenerative and osteolytic changes
the joint components are undergoing in these conditions make
these components of the TMJ highly susceptible to failure under
the new functional loading resulting from orthognathic surgical
repositioning of the maxillofacial skeleton.
Osseodistraction
Van Strijen et al. (2001) advised that, since osteoclastic activity
in the TMJ has been reported after gradual distraction of the
mandible, distraction osteogenesis may make its own
contribution to TMJ-osteoarthrosis and idiopathic condylar
resorption. They suggested that, in the future, persons being
considered for surgical management of mandibular hypoplasia
be critically evaluated for any traumatic, functional, or
metabolic risk factors for TMJ-osteoarthrosis and idiopathic
condylar resorption.
Salvage Procedures—Total Joint Replacement
The costochondral graft has been the autogenous bone most
J Dent Res 87(4) 2008 Degenerative Disorders of the TMJ
frequently recommended for the reconstruction of the TMJ, due
to its ease of adaptation to the recipient site, its gross anatomical
similarity to the mandibular condyle, its low morbidity, its
reported low morbidity rate at the donor site, and its
demonstrated growth potential in juveniles (MacIntosh, 2000).
However, orthopedists recommend alloplastic reconstruction
when total joint replacement is required for the management of
a non-growing person affected by either low-inflammatory or
high-inflammatory arthritic disease (Chapman, 2001).
In the TMJ, alloplastic reconstruction has been discussed at
length (McBride, 1994; Mercuri, 1998, 1999, 2000). All of
these authors agree that when the mandibular condyle is
extensively damaged, degenerated, or lost, as in arthritic
conditions, replacement with either autogenous graft or
alloplastic implant is an acceptable approach to achieve optimal
symptomatic and functional improvement. Long-term follow-
up studies include individuals with diagnoses consistent with
low- and high-inflammatory arthritic TMJs in their total
alloplastic reconstruction datasets (Mercuri et al., 2002;
Mercuri and Giobbe-Hurder, 2004; Mercuri, 2006, 2007).
In light of these findings, previously published experience
in both orthopedic and oral and maxillofacial surgery, and the
literature comparing autogenous with alloplastic total TMJ
replacement in arthritic conditions, it appears that total
alloplastic TMJ reconstruction should be considered
appropriate management for advanced-stage TMJ osteoarthritic
disease and idiopathic condylar resorption (Table 2).
LOOKING TO THE FUTURE: TISSUE ENGINEERING
The next generation of TMJ implants will be biological
constructs fabricated with tissue-engineering technology.
Currently, the TMJ disc and the mandibular condyle have been
the focus of tissue-engineering efforts, pursued by only a
limited number of groups in the world. In the long term,
regenerative therapies may need to combine both of these
structures into a single implant, and to expand the focus to
include surrounding structures, such as the retrodiscal tissue
and the fossa-eminence of the temporal bone (Detamore et al.,
2007). However, the disc and condyle are the highest priority
for clinical application.
TMJ Disc Tissue Engineering
To date, tissue-engineering investigations of the disc and the
condyle have been conducted independent of one another. Both
the condyle and disc tissue-engineering communities have
made significant advances in recent years, although the disc
investigations began much earlier. Four TMJ disc tissue-
engineering studies were published from 1991 to 2001
(Detamore and Athanasiou, 2003), and while important issues
were addressed, such as cell source, biomaterials, and shape-
specific scaffolds, the common theme among these pioneering
studies was an unfamiliarity with the available characterization
data for the TMJ disc in terms of cell content and matrix
composition. In 2001, strategies for TMJ tissue engineering,
including cell sources, scaffolding materials, and signaling,
were reviewed (Glowacki, 2001), and a photopolymerization
method for developing a shape-specific TMJ disc scaffold was
developed (Poshusta and Anseth, 2001). However, it took 3
years before the next wave of TMJ disc tissue-engineering
studies was published, all of which utilized cells derived from
the TMJ disc. Most of these studies were from Athanasiou's
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303
group, which collectively supported the use of polyglycolic
acid over agarose (Almarza and Athanasiou, 2004), promoted
the spinner flask as the preferred seeding method with
polyglycolic acid scaffolds (Almarza and Athanasiou, 2004),
demonstrated the importance of using growth factors such as
insulin-like growth factor-I (Almarza and Athanasiou, 2006b;
Detamore and Athanasiou, 2005a), revealed the detrimental
effects of passaging and pellet culture (Allen and Athanasiou,
2006b), recommended 25 ␮g/mL as a preferred ascorbic acid
concentration (Bean et al., 2006), and investigated the effects
of hydrostatic pressure (Almarza and Athanasiou, 2006a) and
rotating wall bioreactors (Detamore and Athanasiou, 2005b).
Recently, another study has suggested the use of platelet-
derived growth factor-BB in TMJ disc tissue engineering
(Hanaoka et al., 2006).
Overall, the TMJ disc tissue-engineering studies to date
have utilized various cell sources and biomaterials, evaluating
the effects of different bioactive signals and bioreactors. The
next major investigations into TMJ disc tissue engineering will
be the incorporation of stem cell sources and the evaluation of
in vivo performance of engineered TMJ discs.
Mandibular Condyle/Ramus Tissue Engineering
Unlike the TMJ disc, mandibular condyle/ramus tissue-
engineering studies did not appear in the literature until this
decade. The largest contributions, thus far, have come from the
groups of Hollister and Mao. Beginning in 2000, Hollister and
colleagues developed a strategy for producing person-specific
condyle-shaped scaffolds based on computed tomography
and/or magnetic resonance images. By using solid free-form
fabrication, they have been able to control not only the overall
shape, but also the internal architecture, providing for precise
control over pore size, porosity, permeability, and mechanical
integrity. Solid free-form fabrication methods such as
stereolithography and selective layer sintering work by creating
scaffolds layer by layer. In this manner, Hollister and
colleagues have engineered cylindrical osteochondral
constructs (Schek et al., 2004, 2005) and condyle/ramus-
shaped bone constructs (Williams et al., 2005), using materials
such as hydroxyapatite, polylactic acid, and polycaprolactone
and mature cell sources (fibroblasts with bone morphogenic
protein-7 gene inserted and/or chondrocytes). In vivo studies
collectively demonstrated substantial bone ingrowth and
glycosaminoglycan formation (Schek et al., 2004, 2005;
Hollister et al., 2005; Williams et al., 2005). Mao's group
(Alhadlaq and Mao, 2003, 2005; Alhadlaq et al., 2004) has
taken a different approach, encapsulating marrow-derived
mesenchymal stem cells in a polyethylene glycol diacrylate
hydrogel to create stratified bone and cartilage layers in the
shape of a human condyle. After 12 weeks in vivo, it was
shown that osteopontin, osteonectin, and collagen I were
localized in the osteogenic layer, and collagen II and
glycosaminoglycans were localized in the chondrogenic layer
(Alhadlaq and Mao, 2005).
Beyond these two primary groups, various different
approaches have been used, most of which were in vivo studies
using only histology and/or imaging to validate engineered
constructs. A pair of studies molded coral into the shape of a
human condyle and seeded it with mesenchymal stem cells,
then implanted it either with bone morphogenic protein-2 in
mice, to demonstrate osteogenesis (YJ Chen et al., 2002), or
304
under blood vessels in rabbits, to demonstrate construct
vascularization (Chen et al., 2004). Another pair of studies
implanted acellular poly(lactic-co-glycolic acid)-based
constructs with growth factors in rat mandibular defects,
demonstrating either the efficacy of transforming growth
factor-␤1 and insulin-like growth factor-I (Srouji et al., 2005)
or the lack of efficacy of bone morphogenic protein-2 (Ueki et
al., 2003) under the prescribed conditions. In another case,
osteoblasts were seeded into condyle-shaped polyglycolic
acid/polylactic acid scaffolds, and chondrocytes were painted
on the surface prior to implantation in mice, after which
positive histological results were observed (Weng et al., 2001).
In a related study, porcine mesenchymal stem cells seeded in
condyle-shaped poly(lactic-co-glycolic acid) scaffolds were
cultured under osteogenic conditions in a custom-built rotating
bioreactor, which also yielded positive histological results
(Abukawa et al., 2003). Finally, a recent study compared
human umbilical cord matrix mesenchymal stem cells with
porcine condylar cartilage cells for condylar cartilage tissue
engineering, showing that the umbilical cord matrix stem cells
outperformed the cartilage cells, especially with regard to
proliferation and to chondroitin sulfate and overall
glycosaminoglycan synthesis (Bailey et al., 2007).
The next major step for mandibular condyle/ramus tissue
engineering will be demonstrating long-term in vivo efficacy
with osteochondral condyle/ramus replacements in larger
animals (e.g., pig), which will require an understanding of the
growth and mechanics of the native tissue (Herring and
Ochareon, 2005).
Future Directions in TMJ Tissue Engineering
Despite its short history and the relatively few published
reports, significant advances have already been made in TMJ
tissue engineering. At this stage, we are still several years away
from bringing tissue-engineering technology to the clinic for
individuals with TMJ. Although it would be premature to
speculate as to how and when these models can be applied to
humans, there are nonetheless areas of pressing clinical interest
that have been identified for the near future. In particular,
primary issues to be addressed in the coming years include
attachment, integration, metaplasia, angiogenesis, the person's
age, marketing, and creating a condyle-disc composite scaffold
(Detamore et al., 2007). Biomechanical models of the TMJ are
becoming highly sophisticated, especially with recent additions
to the literature characterizing tissue properties, which will be
invaluable in predicting mechanical design requirements for
engineered constructs.
CONCLUSIONS
The importance of developing an evidence-based approach to
clinical management and treatment must be emphasized. Often,
in the past, treatment of clinical disorders has been based
purely upon experience and knowledge gained through clinical
training. This often resulted in various management modalities
for the same condition, as well as in ineffective, expensive,
unvalidated, and sometimes potentially harmful interventions.
The goal of evidence-based medicine is to move beyond
anecdotal clinical experience by bridging the gap between
research and clinical practice.
With respect to the degenerative pathology of the TMJ, the
treatment goals for affected individuals include restored
function and pain reduction. The management modalities used
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International and American Associations for Dental Research
Tanaka et al. J Dent Res 87(4) 2008
to achieve these goals can range from non-invasive therapy, to
minimally invasive and invasive surgery. Most people can be
managed non-invasively, and one must acknowledge the
importance of disease prevention and conservative
management in the overall treatment of persons with TMJ. The
decision to manage TMJ-osteoarthrosis surgically must be
based on evaluation of the person's response to non-invasive
management, his/her mandibular form and function, and the
effect of the condition on his/her quality of life.
To date, although systemic illness, aging processes,
hormonal factors, and behavioral factors have been implicated
in the etiology of TMJ-osteoarthrosis, growing evidence
suggests that mechanical overload may be assumed to be an
initiating factor for a series of degenerative changes in the
TMJ, resulting in condylar resorption and deformity. Therefore,
an evaluation of the biomechanical environment in the TMJ
would lead to a better understanding of the inducing
mechanism of TMJ pain and disability, which result in proper
diagnosis and available treatment planning for TMJ
degenerative disorders.
A proper understanding of the biomechanical behavior of
the joint components and biomechanical environment within
the TMJ also provides better focus in the search for and
selection of mechanically compatible synthetic or regenerative
biomaterials for TMJ reconstruction. While tissue engineering
may revolutionize the future of TMJ treatment, it will be
absolutely necessary to remember the lessons learned from
decades of successes and failures with TMJ implants.
Moreover, tissue-engineered joint structures may be doomed to
failure unless the etiology of the underlying degenerative
processes is identified and managed. Therefore, an
understanding of the pathobiology of TMJ degenerative
disorders and current clinical treatment, as described in this
article, will be essential to the successful integration of tissue
engineering into the future surgical management of TMJ
pathology.
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