Vocal Fold Scars Current Concepts and Future Directions

Eur Arch Otorhinolaryngol
DOI 10.1007/s00405-013-2498-9
LARYNGOLOGY
Vocal fold scars: current concepts and future directions.

Consensus report of the phonosurgery committee of the European
laryngological society
G. Friedrich F. G. Dikkers C. Arens M. Remacle
M. Hess A. Giovanni S. Duflo A. Hantzakos
V. Bachy M. Gugatschka
Received: 1 October 2012 / Accepted: 11 April 2013

Springer-Verlag Berlin Heidelberg 2013
Abstract Scarring of the vocal folds leads to a deterioration of the highly complex micro-structure with consecutively impaired vibratory pattern and glottic insufficiency.
The resulting dysphonia is predominantly characterized by
a reduced vocal capacity. Despite the considerable progress
in understanding of the underlying pathophysiology, the
treatment of scarred vocal folds is still an unresolved
chapter in laryngology and phonosurgery. Essential for a
successful treatment is an individual, multi-dimensional
concept that comprises the whole armamentarium of surgical and non-surgical (i.p. voice therapy) modalities. An
ideal approach would be to soften the scar, because the
reduced pliability and consequently the increased vibratory
rigidity impede the easiness of vibration. The chosen
phonosurgical method is determined by the main clinical
G. Friedrich M. Gugatschka (&)
Department of Phoniatrics, ENT University Hospital Graz,
Speech and Swallowing, Medical University Graz,
Auenbruggerplatz 26, 8036 Graz, Austria
e-mail: markus.gugatschka@klinikum-graz.at
F. G. Dikkers
Department of Otorhinolaryngology, University of Groningen,
University Medical Center Groningen, Groningen,
The Netherlands
C. Arens
Department of Otorhinolaryngology, University Hospitals
Magdeburg, Otto-von-Guericke University, Magdeburg,
Germany
M. Remacle
Louvain University Hospital of Mont-Godinne, Dinant, Belgium
feature: Medialization techniques for the treatment of

glottic gap, or epithelium freeing techniques for improvement of vibration characteristics often combined with
injection augmentation or implantation. In severe cases,
buccal mucosa grafting can be an option. New developments, include treatment with anxiolytic lasers, laser
technology with ultrafine excision/ablation properties
avoiding coagulation (Picosecond infrared laser, PIRL), or
techniques of tissue engineering. However, despite the
promising results by in vitro experiments, animal studies
and first clinical trials, the step into clinical routine application has yet to be taken.
Keywords Phonosurgery Vocal fold scars Sulcus
vocalis Vergeture Vocal fold medialization Micro-flap
A. Giovanni
Service ORL Et Chirurgie Cervico-Faciale, Centre Hospitalier
Universitaire La Timone, Marseille, France
S. Duflo
Department of Otorhinolaryngology, Head and Neck Surgery,
` Pitre, Guadeloupe, France
University Hospital of Pointe A
A. Hantzakos
1st Department of Otolaryngology, Head and Neck Surgery,
University of Athens Medical School, Hippokration General
Hospital, Athens, Greece
V. Bachy
Department of Head and Neck Surgery, Division
Otolaryngology, Catholic University of Louvain at MontGodinne, Louvain, Belgium
M. Hess
Department of Voice, Speech and Hearing Disorders, University
Medical Center Hamburg-Eppendorf Hamburg, Hamburg,
Germany
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technique Buccal mucosa grafting Laser Tissue

engineering
Introduction
Vocal fold (VF) scarring results from an injury to the layered structure of the VF and leads to a significant impairment in vibration characteristics. It alters its visco-elastic
properties and leads to a dysphonic, often breathy and little
sustainable voice and has a considerable impact on the
quality of life. Main features of VF scarring are disorganized collagen and elastin bundles, loss of important ECM
(extra-cellular matrix) constituents, volume deficiency,
reduced VF pliability and glottal insufficiency [1]. The
treatment of scarred VFs is still an unresolved chapter in
laryngology and is mainly caused by the highly complex
micro-structure of the VFs, especially the tri-layered
structure of the human lamina propria. Comprehensive
knowledge about this highly specific ultra-structure and the
molecular mechanisms of VF injury are the background for
every profound treatment modality. Research in this field
has emerged the last years, giving deeper insights and new
understandings of the complex interplay between interstitial
proteins (e.g. fibronectin, decorin, fibromodulin), glycosaminoglycans (e.g. hyaluronic acid [HA]) and various
extracellular matrix fibers (e.g. collagen, procollagen,
elastin) [1, 2]. The proportions, relationship and organization of ECM components determine to a large degree the
biomechanical properties of the VFs. However, main focus
of research and experiments was on animal trials, with only
a handful studies carried out in humans [3, 4].
In his landmark paper, Minoru Hirano described the
body-cover model of phonation as the morphological basis
for self-sustaining periodic VF vibrations and a consequently undisturbed voice sound [5]. Epithelium, basement
membrane zone [6] and the superficial layer of the lamina
propria (SLP) form the cover. They share similar
mechanical properties and behave collectively as one
functional unit. The deep layer of the lamina propria (DLP)
is firmly attached to the vocalis muscle, both are referred to
as body. The transitional zone lies between the two and
consists of the middle or intermediate layer of the lamina
propria (MLP) (Fig. 1a). This specific architecture with
two functional units enables the superficial cover to oscillate independently from the deeper lying body. The amount
of tissue in vibration depends on pitch, loudness, but is also
influenced by age [7].
The basement membrane zone serves as junction
between epithelium and lamina propria. Gray et al. [6]
described collagenous anchoring fibers in the basement
membrane zone that help in securing basal cells to the SLP
(Fig. 1b). The SLP is also known as Reinkes space. This
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important structure plays a crucial role in decoupling the

mucosal cover from the VF body. Reinkes space is absent
at the anterior commissure and the posterior end of the
VFs. Situated at both extremities of the VFs are the nucleirich centres of proliferation, the anterior and posterior
macula flava [811]. The superficial layer consists mainly
of amorphous material, with only few collagen and elastin
fibers. The intermediate layer is characterized by a higher
amount of elastic, the deep layer by an increased amount of
collagenous fibers [7]. This laminated structure is present
in the freely vibrating membranous mid-part of the VF, but
changes its structure near the attachments of the VF to the
anterior and posterior macula flava (syn.: nodulus elasticus). These transition zones consist of interwoven bundles
of collagen and elastic fibers, having the function of a
cushion ball during vibration [12]. Tillmann et al. [13]
compared these structures with a traction spring that protects the attachments of the VF and balances the different
elasticities between the vibrating VF and the stiff laryngeal
framework. The lengths of the different zones show significant sex related differences [9] (Fig. 2). The delicate
architecture has not only functional consequences in terms
of voice outcome, but has a significant impact on surgery
of the VFs. Phonosurgery of the SLP generally heals better
than surgery that penetrates into the deeper layers [14].
Micro-physiology of vocal fold injury

The cell-rich maculae flavae can be considered as the cell
reservoir of the VFs. These areas play a crucial role during
growth [15, 16], but also in both acute and chronic
inflammation processes. Throughout the VFs, few spindleshaped fibroblasts are present. They are mainly inactive
under normal conditions. In contrast, the morphology and
quantity of fibroblasts in the anterior and posterior macula
flava differ significantly: Stellate-formed fibroblasts can be
found here that actively synthesize collagenous, elastic and
reticular fibers, as well as the glycosaminoglycan hyaluronic acid (HA) [17]. More recent studies proved the
presence of stem cells in these areas: Studies in rats VFs
showed that stem cells migrate after injury from the maculae flavae to the region of the lesion with a peak after
57 days [18, 19]. Ultrastructural studies of scarred ferret
VFs described larger fibroblasts as compared to those
found in normal VFs. These are assumed to be myofibroblasts that produce abundant amounts of type I collagen
[20].
Collagen fibers have been regarded as the most important constituent in scar tissue [21]. Collagen synthesis was
found to be unregulated between 3 and 6 weeks postinjury. In contrast to normal VFs, where collagen fibers run
parallel to the epithelial lining, this characteristic
Fig. 1 Layered structure of the vocal folds (a) and basement membrane zone according to Gray (b) [6]
organization is lost and replaced by deposits of thick collagen bundles throughout all layers of the lamina propria.
Their density is significantly reduced as compared to normal VFs [21, 22]. The precursor of collagen, procollagen 1,
was found to be increased in the SLP of injured VFs.
Although levels of procollagen one decreased to pre-injury
levels after 6 months, densities of collagen remained elevated [21]. Native collagen type 3, which is of finer caliber
and the predominant type before injury, is replaced
throughout the healing process by the molecularly and
microscopically different collagen type I [23]. Elastin was
found to be reduced in VF scars with its architecture
scattered [1, 24].
Levels of HA have a significant impact on viscoelastic
properties of the VFs and play a decisive role in wound
healing and scarring [25, 26]. It has been shown that elevated levels of HA favor wound healing and diminish
scarring as can be observed in scarless fetal wounds [27].

HA plays an outstanding role in determining the biomechanical properties of the VFs. The removal of HA led to
increased viscosity and reduced stiffness with detrimental
effects on oscillation behavior [26]. Experiments in rabbits
revealed decreased levels of HA during the 1 days after VF
injury, although a relative peak was found after 5 days
when compared with uninjured VFs. This decrease is
thought to play a negative effect on wound healing and
may contribute to formation of scar tissue [27]. However,
one has to keep in mind that in experiments of chronic scar
formation significant differences between various animal
studies can be found [3].
Fibronectin is a glycoprotein of the ECM that acts as an
adhesion and migration molecule during repair processes. It
furthermore acts chemotactic for inflammatory cells and
fibroblasts and contributes to matrix organization [2]. In
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Fig. 2 Absolute and relative dimensions of the glottis and their sex related differences. Zones: I lat wall of the post glottis, II vocal process, III
post macula flava, IV freely vibrating midpart, V ant macula flava. Asterisks indicate statistically significant sex related differences (p \ 0.05) [9]
normal VFs this glycoprotein is usually found in the basement

membrane zone and SLP. Levels of fibronectin remained
elevated as long as 6 months after injury in VF tissue (rabbit
and canine experiments) [28]. Recent studies suggest a complex interplay of numerous other glycoproteins. Increased
levels of fibronectin are associated with elevated levels of
collagen synthesis (due to decreased fibromodulin, which
allows collagen regulation) and disorganized collagen deposition (due to decreased decorin) [2]. Decorin is another
adhesion molecule of the ECM that maintains collagen fibril
organization. It is assumed to inhibit cell adhesion and
migration through interactions with beta-integrins. Decorin
density was significantly reduced in scarred rabbit VFs
60 days after injury [29]. It is currently assumed that adequate
levels of decorin counteract the disorganized structural
regrowth of collagen fibers into scar tissue.
Etiopathogenesis
Origins of VF scarring can be either congenital or acquired,
with the last one to be far more common. Bouchayer and
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Cornut published 1985, an elaborated concept of congenital

VF lesions, suggesting epidermoid cysts as a common
cause for different pathologic conditions [30] (Fig. 3).
They hypothesized that epidermoid cysts result from
residuals of the fourth and six branchial arches. According
to their theories sulcus vocalis and what they refer to as
vergeture, results from a rupture of those epidermoid cysts.
If the ruptured VF cyst penetrates on both sides (superior
and below the free margin of the VF) the mucosa between
these two openings turns into a mucosal bridge [30, 31].
They underlined their theory with the typical early onset of
this kind of dysphonia during childhood, familial occurrence, simultaneous findings of multiple lesions in both
VFs and association with other malformations, such as
pathological vessels and micro-webs.
Ford classified sulcus vocalis into three subtypes [32]:
type I is a physiologic variant accentuated by atrophy, but
with intact lamina propria and an undisturbed mucosal
wave. Type II (sulcus vergeture) is characterized by disappearance of a functional SLP. In most cases, the bottom
of the vergeture is attached to the vocal ligament and leads
to moderate dysphonia. Type III true sulcus (pouch)
Fig. 3 Congenital lesions according to the concept of Bouchayer and

Cornut [30]
extends more deeply into the vocal ligament and may even
penetrate into the thyroarytenoid muscle. It disrupts the
mucosal vibration and leads to severe dysphonia [33]. The
incidence of sulcus vocalis seems to be considerably high:
a recent study performed in 100 cadavers found sulcus
vocalis in 39 cases with a pathological sulcus vocalis rate
of 23 [34].
Other authors have suggested that sulcus vocalis is
acquired and results from local trauma and/or chronic
inflammatory processes [35, 36]. Sato and Hirano [37]
demonstrated that sulcus vocalis is associated with a
degeneration of fibroblasts in the macula flava. Collagenous and elastic fibers, synthesized by fibroblasts in the
maculae flavae, were decreased. They described the presence of many abnormal elastic fibers in the maculae flavae.
This mechanism is similar to the age-related degeneration
of the VFs. Giovanni [33] concluded that congenital and
acquired lesions are complementary and that the decisive
link is a specific weakness in the regulation mechanisms of
fibrous tissue in the VF.
The most common cause for VF scars are sequelae after
traumatic injuries by heterogenic mechanisms including
external laryngeal trauma (fracture), internal laryngeal
trauma (intubation) and phonotrauma as well as phonosurgery. In cancer surgery extended resection of VF tissue
with consecutive heavy scarring is mostly inevitable.
Surgery for benign VF lesions has to avoid this by any

means by carefully respecting phonosurgical principles, as
inadequate techniques and wrong indications can have
disastrous consequences for the patient [38, 39]. Special
care must be taken of the very trauma-sensitive SLP. A
rias et al. [40] reported on adherent
study by Martinez-A
epithelium to the deep VF tissue after laser-assisted surgery
(CO2 laser scanning technology) of benign lesions in 12
patients. Thermal trauma can damage the delicate lamina
propria very easily. On the other hand, carefully conducted
studies by Benninger [41] and Remacle [42] could prove
that there are no differences in the functional outcomes
between CO2 laser and cold instrument surgery in benign
VF lesions when proper settings and techniques are used.
Other causes for acquired VF scars are chronic inflammatory processes due to laryngo-pharyngeal reflux, smoking,
radiotherapy, toxic inhalants etc. The aging process of the
VFs does not necessarily lead to scars, but very often to
similar conditions by a combination of VF atrophy and an
accumulation of lifelong traumas.
One must state, however, that there is no general accepted
classification of VF scars. Benninger et al. [43] distinguished
the following causes of VF scarring: traumatic, neoplastic,
iatrogenic, inflammatory and miscellaneous.
With respect to the severity of scar formation, Arens and
Remacle [44] divided glottic scars into four types:
Type I Mild to moderate glottic insufficiency and
reduced vibrations of the vocal folds. The scar involves the
mucosal and submucosal levels of the vocal fold.
Type II Anterior moderate glottic insufficiency, seen
around the anterior commissure region. The scar involves
the vocalis muscle. No vibrations of the VF.
Type III Considerable glottic insufficiency. The scar
formation is adherent to the inner perichondrium and the
cartilage. The defect extends up to the supraglottic region,
twisted arytenoids may be noticed.
Type IV Considerable glottic insufficiency. Web formation at the anterior commissure region. Bilaterally
reduced vibrations of the VFs.
Diagnosis
Patients usually present clinically with long lasting dysphonia, vocal fatigue, loss of vocal control and a breathy,
little sustainable, dysphonic voice. In addition to a thorough medical history, meticulous laryngoscopy and videolaryngostroboscopy using rigid and/or flexible
endoscopes are indispensible for a proper diagnosis. Some
of the scars can be apparent and evident, thus needing
little effort to identify, as in cases following cordectomy.
Others can be difficult to assess as in cases of sulcus and
subepithelial adhesions.
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Two major clinical features are typical for scarring: (1) a

spindle-shaped glottis during phonation with insufficient
glottic closure and air leakage and (2) an impaired VF
vibration with reduced amplitude and reduced or mostly
absent mucosal wave. Vibrations are mostly asymmetric
and irregular. Especially when it comes to planning of
treatment, it is essential to distinguish between two major
findings: rigidity and/or insufficient glottic closure. Additional signs that should raise attention are: dilated or
pathological vessels on the surface of the VFs, thickening
of the epithelium, chronic inflammatory signs, or supraglottic hyperfunction.
It is important to take into consideration that minimal
lesions maybe easily overseen in indirect laryngoscopy or
by stroboscopy and that these patients are often misdiagnosed with functional dysphonia. Especially in cases of a
very aperiodic voice signal, high-speed cinematography or
kymography can provide valuable additional information.
For exact diagnosis and therapeutic planning, a direct microlaryngoscopy with palpation of the VFs with microinstruments is a prerequisite [33] (Fig. 4a, b). A full voicelab work up including voice recordings, auditory perceptual analysis and patient-perceived outcome measures (i.e.
voice handicap index VHI) is regarded standard before
treatment [45].
prophylaxis and early management of scarring [43]. A

variety of treatment options have been developed in the last
decades. Despite all efforts, it has not been possible to date
to completely restore an unaltered VF structure and oscillation. From a functional view, the SLP is the crucial
structure of the VF and the creation of a new gliding zone
remains one of the major unsolved problems in
phonosurgery.
The patient has to be informed meticulously that the
options for improving the voice sound are very limited and
that the major aim of all therapeutic procedures is primarily
to increase loudness and vocal endurance and furthermore
to reduce air loss and vocal fatigue [38]. Surgery should not
be performed within 6 months after the formation of scar
when the healing process is not yet complete [40]. As the
objective of surgery is to improve glottic closure and pliability of the VFs, the treatment facilities should be orientated towards the main clinical feature, either glottic gap
and/or rigidity.
Treatment
Medialization thyroplasty
Because surgical treatment is usually very difficult and the

therapeutic outcome is to some extent unpredictable, conservative therapy should be the first line of treatment.
Voice therapy alone can be effective and satisfactory, but it
might also be given as a supplementary postoperative
treatment modality. It is usually based on the traditional
holistic concepts primarily focusing on resonatory voice
and breath supported voice coordination. Anti-reflux therapy, antibiotics and steroids occasionally play a role in
The principle of medialization thyroplasty is to excise a

thyroid cartilage window corresponding to the position of
the VF in the endolarynx and to insert an implant through
this window which medializes the VF (Fig. 5). The main
advantage of these techniques is to achieve a spatial reorganization of the glottic framework without touching the
VFs directly thus avoiding any trauma to the VFs with
potential scarring and stiffening. This is of special importance in previously scarred VFs, as thyroplasty usually are
Medialization procedures
In cases, where an insufficient glottic closure is the predominant finding, medialization procedures proved to be
very effective. These can either be performed with medialization thyroplasty or injection augmentation.
Fig. 4 Vergeture (a) and mucosal bridge (b) during explorative direct laryngoscopy (not visible in indirect laryngoscopy)
123
Fig. 5 Principle of vocal fold medialization by medialization

thyroplasty
reversible and hence the danger of postoperative voice

deterioration is minimal as compared to direct VF surgery.
Isshiki [4648] introduced a hand-carved silastic bloc
which is still widely used. Nevertheless, a variety of surgical modifications and different implants regarding
material and shape has been developed over time [4953].
The major indication for medialization thyroplasty is a
unilateral VF paralysis, but its effectiveness has also been
proven in glottic insufficiency due to atrophy and/or scarring [33, 5458]. In cases of bilateral VF bowing, the
implantation procedures can be performed bilaterally. The
implant stays in place and ensures a permanent improvement even in larynges with normal mobility, where injected materials usually tend to spread [47, 59]. In very stiff,
VFs a combination of medialization thyroplasty and
relaxation laryngoplasty can lead to further voice
improvement. A special advantage of laryngeal framework
surgery under local anesthesia is that it allows a fine tuning
by listening to the positive change happening to the voice
of the patient on table while performing different framework surgery procedures in combination [47, 55].
Especially for VF medialization after chordectomy,
Sittel et al. [60] developed a procedure where after resection of the upper rim of the thyroid cartilage a subpericondral pouch is created. The harvested cartilage is reimplanted in that pocket to achieve a VF augmentation and
consequent voice improvement.
Injection augmentation
Injection augmentation was introduced by Brunings [39] in
1911 and was the first real phonosurgical procedure ever. It
was primarily designed for the treatment of unilateral VF
paralysis. A large number of injectable fillers have been in
use over time, which indicates that there is still no ideal
substance for injection augmentation available [61]. Usually, fillers are injected under general anesthesia during
microlaryngoscopy, but office-based procedures become
increasingly popular particularly for temporary injections.
In a multi-institutional retrospective study, Sulica et al.
[62] reviewed 460 patients with regard to the current
practice in injection augmentation in the US. Out of the

460 patients, nearly half were treated in the operating
room, whilst the other half were treated unsedated in
office-based procedures (transcricothyroid approach, peroral approach, transthyrohyoid approach, or transthyroid
cartilage approach). The indications were paralysis in 75 %
VF, VF atrophy in 15 % and scar formation in 10 %. Scar
was more likely to be treated in the operating room.
Basically, two groups of fillers can be distinguished: alloplastic and autologous/xenogenic materials.
In general, alloplastic materials are non-biodegradable
fillers aimed to stay in place permanently. They have the
disadvantage that in case of an unfavorable postoperative
result (e.g. by inadvertent placement) the removal of the
injected substance is difficult and leads to severe trauma of
the VF. In addition, long-term side-effects, such as foreign
body reactions, or granuloma formation cannot be totally
excluded, as observed in cases of silicone injections or of
the meanwhile obsolete Teflon [63]. These substances have
to be injected far lateral near to the thyroid cartilage
(internal thyroplasty). A superficial injection must be
strictly avoided as this might lead to a stiffening of the VFs
with resultant dysphonia (Fig. 6a, b). Alloplastic fillers
currently approved for VF medialization are Vox Implant
on a silicon basis (polydimethylsiloxane particles) [64] and
Radiesse on a calcium hydroxylapatite basis [65]. Alloplastic fillers did not show promising results in the treatment of VF scars, where laryngeal framework surgery
proved to be superior [66].
Following the application in urology, Sittel et al. [64]
introduced, among others, the use of textured polydimethylsiloxane particles (PDMS particles: Vox
Implant) in the human larynx for injection augmentation.
With the desirable viscoelastic properties near to Teflon,
PDMS particles did not show the detrimental tendency of
implant migration and foreign body reaction. This is due to
their biomechanical properties of a particle size of about
200 lm that prevents from being phagocytosed. As the
implant procedure is irreversible, injection under general
anesthesia is generally recommended. Improvement of
voice outcome and acoustic parameters were described
similar to those of framework surgery [67]. However, longterm studies dealing with persistence are lacking in this
field.
Synthetic calcium hydroxylapatite (CaHA: Radiesse
Voice) is available as Radiesse Voice [65]. Among its
favorable characteristics are its biological inertia and easy
application even through a small-gauge needle. Carroll and
Rosen [63] proved its excellent rheological properties, as
well its longevity. Average length of benefit was
19 months in 108 patients. Complications included theoretically (as in most fillers) implant migration, granuloma
formation, VF mucosa irregularities, allergic reactions and
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Fig. 6 Lateral injection for vocal fold augmentation (a), situation after false medial injection of polydimethylsiloxane causing vocal fold
stiffness during surgical removal (b)
ectopic calcifications. In the aforementioned study, only

one case of implant migration was described in 108
injections, which required surgical removal. As with other
permanent fillers, only patients with permanent paralysis of
the VFs are supposed to be treated. In cases, where a nerve
recovery is suspected, short-term treatment (suitable for
12 months) by an injectable consisting of synthetic
polymers (carboxymethylcellulose) without CaHA microspheres became recently very popular (Radiesse Voice
Gel) [68].
Autologous materials have the big advantage of providing usually excellent biocompatibility, but are characterized by a certain resorption rate depending on the
material and site of injection.
The most common autologous fillers used so far for
treatment of VF scarring are autologous fat and fascia.
Numerous papers have been published dealing with fat
injection, with a strong preference on lateral fat injection
compared to implantation near the vibratory margin [69].
Fat autografts are easy to harvest and show only minimal
immunological reactivity [70]. Animal studies demonstrated improved (decreased) threshold pressures of phonation, increased sound intensity and more effective
acoustic output [71]. Furthermore, Titze et al. [72] showed
that fat injections are favorable to collagen, or Gel-Foam
because its viscoelastic properties are closer to human
mucosa. A retrospective literature review from 2009
proved this method to be very safe, with over-injection of
fat as a reversible complication in only three, and only one
single case of granuloma formation out of totally 88
patients [73]. One single paper reported neck abscess following lipoinjection [74].
Glottic gap insufficiency diminishes after injection as
the VF is placed medially and additional bulk is added to
the VF. Videostroboscopic studies underline this
123
significantly [7577]. Videostroboscospic parameters of

the aforementioned studies included mucosal wave propagation, stiffness (both improved), length of scar and ectasia
(both no improvement). In addition, acoustic and perceptual improvements were reported by the same authors. The
results showed an overall mean increase in fundamental
frequency and phonatory time, whereas jitter and shimmer
values decreased. Breathiness improved in most studies [2,
77].
Rihkanen [78, 79] introduced in 1998 the injection of
minced autologous fascia primarily for treatment of VF
paralysis. Fascia [80] is either used alone as an implant, or in
combination with fat [81]. Here again, satisfying results
have been described stroboscopically regarding a sufficient
glottic closure, mucosal wave, amplitude, breathiness and
overall voice rating. Nevertheless, a laterally placed overinjection of about 30 % was recommended as fat is reabsorbed to a certain degree [75, 82, 83]. In contrast to fat
injection, fascia grafts seem to survive longer as shown by
good voice results even after 36 months [80]. Reijonen et al.
[80] showed stable results after injection over 310 years.
Collagen-based fillers were introduced in the late 1980s
[84, 85]. Due to its bovine basis, potential immunologic and
infectious reactions remained the main objective to use these
fillers. Later on injectable, autologous collagen derived from
human skin from cadavers was introduced (Cymetra).
These were classified as level IV human allografts by the
World Health Organization. However, Hertegard et al. [83]
found comparable outcomes for collagen and hyaluronic
acid in terms of voice improvement, resorption rates and
side-effects. At the moment, collagen is no longer commercially available in the majority of countries.
Hyaluronic acid (HA) is a glycosaminoglycan that is
present in the extra-cellular matrix of most tissues
throughout the body, including the VF mucosa. Several HA
derivatives have been developed and some are in laryngological use mostly in Europe. Modern HA products are of
bacterial origin and chemically cross-linked to ensure low
antigenicity and long residence time. The grade of crosslinking can be tuned bio-chemically thus determining the
rate of degradation and hence durability and viscoelasticity
[86]. Minimal inflammation could be seen after injection,
although durability in tissue can be up to 1 year with certain products. Furthermore, HA showed to have positive
effects on viscoelasticity of scarred VFs in rabbit trials [87,
88]. First in vivo trials in humans showed that autocrosslinked hyaluronan gel injections into the lamina propria not only act as an augmentation agent, but also as an
anti-adhesive product. Postoperative adhesion and scar
formation was significantly reduced by deposition of HA
derivatives in the lamina propria [8991].
Implantation augmentation
This kind of surgery is indicated when glottic or transglottic
scars with a huge substance gap are present (see thyroplasty). The connective tissue underlying the mucosa may
be adherent to the thyroid cartilage. During microlaryngoscopy or transcervically, a vocal pouch at the inner surface of the thyroid with its maximum at the glottis level is
created. Scars can be freed or dissected. The pouch is filled
up with cartilage (nasal septum, thyroid cartilage) or fascia
lata. After sufficient augmentation, the pouch is closed with
microsutures to stabilize the implant. The procedure can be
performed in several steps to get a sufficient glottis closure
and improvement of the patients voice [44].
Epithelium freeing techniques and combined
approaches
When rigidity is the major feature, the mucosal wave can
beat least theoreticallyrestored by lysing the scarred
mucosa and creating a new lose layer between the epithelium and the vocal ligament to restore the bodycover
relationship. The introduction of the microflap and later
mini-microflap has revolutionized microphonosurgery as it
respects the layered structure of the VF [92, 93]. A subepithelial saline injection prior to surgery can be very
helpful in this respect to define a dissection plane [94, 95].
Especially for treating sulcus vergeture Bouchayer and
Cornut [96, 97] introduced the freeing of the mucosa
(better: epithelium) technique. After careful dissection of
the epithelium and resection of pathologic tissue, the flap is
turned back and fixated with fibrin glue [30]. With the help
of locally injected cortisone and long-term voice therapy,
they reported good functional results with a re-appearance
of mucosal wave in a high percentage of cases.
Using a micro-flap technique, the flap is usually fixed by
with fibrin glue or micro-sutures (Fig. 7ac). In general,
both methods are considered to be equal in outcome and
the choice is mostly the surgeons individual preference.
Application of commercially available fibrin glue, such as
Tissucol, is impossible in the USA, as it is not FDA (food
and drug administration)approved. Fleming et al. [98]
could show in an animal study that primary closure of
micro-flaps with micro-sutures resulted in less scarring
compared to not closed wounds. This result does not necessarily mean that suturing is superior to glueing, but
proves the importance of covering all denuded areas with
epithelium especially near the vibratory margin. The major
disadvantages of this technique are on the one hand
unpredictable re-adhesion or even the creation of new scars
as no filler or tissue is used for replacement of SLP. On the
other hand, this treatment does not address the glottic gap,
which usually also is present and adds substantially to the
degree of dysphonia. To overcome these shortcomings and
to improve the results, freeing techniques are mostly
combined with injections or implantations that should not
only medialize the VFs but also restore the SLP.
Fig. 7 Freeing of the epithelium: Incision (a) and subepithelial removal of the scars (b), flipping back the epithelium and wound closure with
fibrin glue and/or micro-sutures (c)
123
Injections are performed superficially (medial injection)

and the injectables should not only act as fillers, but also
create a new soft and pliable layer for restoration of the
mucosal wave propagation (Fig. 8). Predominately, autologous fat and low-grade crosslinked HA are used for this
purpose. Recently developed substances in this regard
seem to be Extracel [90] or Carbylan-GSX. The latter is a
filler composed of modified HA and gelatine. The presence
of Carbylan-GSX in the wound bed during the early
stages of repair amplified the normal VF wound-healing
response over a short period of time in rabbit studies [99].
Martinez-Arias et al. [40] follow the same principles but
prefer the CO2 laser scanning technology for raising the
microflap and inject collagen into the deep layer of the
lamina propria. Promising results were reported by Zhang
et al. [100] by implantation of a gelatine sponge combined
with autologous fat for treatment of sulcus vocalis.
Although the absorbable gelatine was used to fill the SLP
to prevent re-adhesion of the detached epithelium, the fat
diminished the glottic gap. With a new laser technology on
the horizon, it is possible to apply ultrafine dissections and
excisions on a cellular level with a pulsed infrared laser at
3 lm. In excised tissue experiments, pulses in the range of
100 picoseconds showed tissue destruction only a few
microns from the dissection line away with virtually no
coagulation zone [101].
Because liquid substances do not remain in the microdissected SLP, Finck introduced esterified hyaluronic acid
as implant into the elevated pocket with excellent results
regarding pliability and mucosal wave [102]. To bring a
healthy and autologous tissue layer between the pathologic
body and cover, which should provide enough cells to
proliferate and renew the pathologic space, Tsunoda et al.
[103] considered the implantation of autologous veins or
fascia as most promising (Figs. 9, 10ad). Based on their
experiences with implantation of autologous fascia,
Fig. 9 After freeing of the epithelium, a subepithelial implantation of

fascia is performed followed by a wound closure with a micro-suture
Tsunoda et al. [104] found that 6 months after the operation there was a consistently improved glottic closure and a
further improvement was recognized after 1 year. At that
time, stroboscopy showed excellent glottic closure
including satisfactory mucosal wave propagation during
phonation. After 3 years of surgery, the presence of
mucosal waves remained at those excellent levels. No
critical complications of the procedure could be observed.
Autologous transplantation of fascia can induce not only
survival but also regrowth of the epithelium. In summary,
they concluded that autologous transplantation of fascia is
a successful surgical procedure for sulcus vocalis and
scarred VFs.
Dedo [105] introduced the concept of fat grafting for
construction of a neo-vocal fold after hemilaryngectomy
and reported good results. Sataloff et al. [75, 106] developed a minimal invasive technique with the creation of
subepithelial tunnels by elevating the scarred mucosa using
blunt and sharp microinstruments. The fat is inserted into
these pockets with a forceps or a laryngeal syringe with a
large diameter needle. The procedure itself resolves the
scar by elevating the mucosa which restores the cover-body
relationship to the VF by the low-viscosity characteristics
of fat. They found an improved wavelike vibration pattern
with more regular periodicities at the free margins.
In an experimental canine study Woo et al. [107]
implanted fat into a submucosal pocket and closed the flap
with microsutures. Larynges were harvested after 6 weeks.
Endoscopic placement of fat into Reinkes space served as
a filler that increased the VF bulk and showed good
vibratory characteristics with restoration of Reinkes layer.
A novel and different approach for the treatment of
sulcus was introduced by Pontes et al. [108] with the
slicing mucosa technique which interrupts the longitudinal
fibrotic tension lines by multiple transverse incisions.
Mucosa grafting
Fig. 8 Medial injection into the lamina propria for medialization and
restoration of a new gliding zone
123
In cases, where the loss of tissue and the amount of scar

formation is so significant that there is no chance for
Fig. 10 Implantation of fascia in a patient: incision and freeing of the epithelium (a), strip of fascia (b), implantation of fascia (c), micro-sutures
(d)
restoration using one of the aforementioned techniques free

buccal mucosa grafting can be an option. Neumann [109]
has used this transplant technique in the 1970s with an
open technique for the treatment of various scar-induced
lesions. Isshiki [110] described in his textbook one similar
case with an open technique via a laryngofissure. The
transplant was fixed in the endolarynx with a rubber stent
for 10 days. In 1990, the first author developed an endolaryngeal technique to fixate an autogenous buccal mucosa
graft that does not require a tracheostomy like the aforementioned techniques [111, 112]. This technique can be
used for restoration of the anterior commissure and/or
replacing the VF mucosa. The rationale behind this technique is to bring healthy, unscarred tissue into the scarred
endolarynx with the aim to create a new vibrating structure
and to fill up tissue defects. First, the area of acceptance has
to be de-epithelialized, favorably using the CO2 laser in the
scanner mode. Oral mucosa is harvested from the inner
cheek. The thickness of the transplant can be chosen
according to the requirements: very thin when only epithelium has to be replaced or full thickness mucosa for
filling up defects. To secure the transplant in the larynx, the
buccal mucosa graft (raw surface outside) is sutured on a
silastic sheet (0.5 mm, fabric reinforced) with Vicryl rapid
3/0. The entire sandwich-graft is attached with one or
two endo-extralaryngeal suture(s) with the Lichtenberger
needle carrier using Prolene 2/0 onto the raw surfaces of

the larynx. The suture is knotted on the skin over an elastic
bolster made out of a folded sheet of silastic which ensures
a good contact of the transplant with the recipient area
(Figs. 11ac, 12ad). After 3 weeks, the silastic sheet is
removed under general anesthesia and granulation tissue
formation can be removed in the same session with the
CO2 laser. It usually takes a few weeks to get a smooth
endolaryngeal surface. Reappearance of vibration takes
several months, but is not guaranteed in every case. If
necessary an additional augmentation or medialization
thyroplasty can be performed after 612 months.
Angiolytic laser
A novel and promising approach for the treatment of scars
is the use of angiolytic lasers i.e. PDL (pulse dye laser) and
PTP (potassium-titanyl phosphate) [113, 114]. A growing
number of papers demonstrated a beneficial effect in
treating cutaneous scars. Although the exact underlying
mechanisms are not fully understood to date, experimental
trials described potential mechanisms of the laser effect,
which includes the development of a sub-basement membrane cleavage plane, as well as up-regulation of proteins
which may actively modulate mature fibrosis [113]. One
prospective pilot study of 11 patients with VF scarring
123
Fig. 11 Buccal mucosa grafting (schematically): resection of the epithelium with laser (scanner mode) (a), situation after resection of the
epithelium and scars (b), sandwich-graft (silastic sheets outside and buccal mucosa graft inside) fixated with an endo-extralaryngeal suture (c)
Fig. 12 Buccal mucosa grafting in a patient: situation after laserchordectomy (type V) with an anterior synechia and scarred substitution vocal
fold (a); situation after resection of the synechia and epithelium with laser (b), sandwich-graft inserted and secured with (blue) endoextralaryngeal sutures (c), 3 month postoperative, synechia is resolved and the fresh mucosa is vital and well integrated, glottic closure and voice
significantly improved (d)
treated with the PDL showed statistically significant

improvement in subjective and objective voice measurements, as well as in laryngeal stroboscopy findings [115].
Tissue engineering
Newer therapeutic approaches aim to restore function on a
cellular basis. These studies are often still under experimental investigation, but larger preclinical studies have
123
been performed, e.g. in the case of hepatic growth factor

(HGF) and treatment is to be expected soon [116, 117].
Modern clinical treatment facilities should not distinguish
between conventional surgery and state-of-the-art bioengineered materials, but are supposed to combine both
approaches. As mentioned before, HA plays a central role
for both maintenance of biomechanical properties and
regeneration after VF injury. HA is degraded enzymatically
by hyaluronidases and has a half-life time of 0.54 days
[118]. Experimental attempts tried to interfere chemically

with the enzymatic degradation of endogenous HA. Both
in vitro and in vivo experiments examined stimulation of
endogenous HA production by administration of external
growth factors; namely, epidermal growth factor (EGF),
basic fibroblast growth factor (bFGF), transforming growth
factor beta 1 (TGFb1) and the aforementioned hepatocyte
growth factor (HGF) [28, 117, 119, 120]. A significant
decrease in collagen deposition and an increase in HA were
noted in acute and chronic settings of VF injury after
injection of HGF in rabbits [116]. Noteworthy, also normal
rat VFs were found to express HGF. In injured rabbit VFs
elevated levels of HGF were detected peaking at day 10 in
the regenerative epithelium [121]. The previous studies
showed that also single administrations of EGF, bFGF and
TGF b1 raised significantly levels of HA for at least 7 days
[119]. In fact, treating VF atrophy (with decreased levels of
HA) with fibroblast growth factor has already been applied
in humans with considerable success [122].
Another possible molecular target are factors that control the phenotype transformation from fibroblasts to
myofibroblasts. One important key molecule is TGF-b, a
factor that is released by inflammatory cells, triggering the
Smad signaling pathway of fibroblasts [123]. Numerous
models targeting inactivation of this pathway have been
established to date [124]. Cell therapy might be the most
powerful tool for treatment of VF scarring. Recent studies
showed highly promising results in the treatment of scarred
rabbits VFs with human mesenchymal stem cells in a
xenograft model. The injected stem cells did not survive
longer than 3 months, but showed beneficial effects in
acute and chronic settings. Improved vibration characteristics with reduced lamina propria thickness and decreased
amounts of type I collagen deposits were found in these
series [87, 125]. But also autologous stem cells derived
from the bone marrow proved their feasibility in woundhealing models in canines [126]. One has to mention,
however, that certain ethical considerations have to be
cleared up before the clinical use of stem cells. Furthermore, the risk of malignant transformation has to be
excluded before implantation of stem cells in humans.
Chhetri went one step further and injected autologous
fibroblasts into scarred VFs of five patients. They observed
improved outcomes after 12 months for mucosal wave
grade and VHI [127].
Conclusion
Because treatment of VF scarring still is a challenge, prevention of scars especially after VF surgery for benign
lesions is of utmost importance. This has to be done by a
meticulous surgical technique carefully respecting the
principles of phonosurgery, which means improvement/

maintenance of the functional structure of the VFs by
respecting its layered structure, minimal excision of tissue,
no epithelial defects especially on the vibratory margin,
minimal trauma to the SLP.
An optimal result does not only require a skilled surgeon
with a broad armamentarium of surgical techniques and
procedures, but a multidisciplinary treatment approach
where phonosurgery must be combined with various nonsurgical methods in a complex treatment program. Most
authors agree that voice therapy should be mandatory not
only postoperatively but also as first-line treatment. Especially in the treatment of VF scars one should always
remember that phonosurgical interventions should never
simply focus on the appearance of the VFs, but aiming at
an improvement of voice adapted to the individual requests
and needs of the patient. As every surgery, it always bears
the risk of an unfavorable outcome with even worsening
the situation by additional scarring. Comprehensive counseling and informed consent are therefore of outstanding
importance.
Because of the unpredictability of the results of the
surgical intervention, it is recommended to start always
with the least traumatizing procedure whenever possible.
This is usually injection augmentation using a re-absorbable material. It allows a good pre-estimation about the
result following a permanent medialization procedure and
has no substantial risk. Carroll and Rosen [128] described
this strategy as trial VF injection. Patients with a good
response to the temporary injectables went on to have
permanent augmentation more often than patients with a
lesser response. In unclear situations it is a good option to
inject saline solution directly in the office which gives an
immediate impression of the result of a medialization
procedure. It takes usually several months to restore a
minimal mucosal wave propagation and long-term postoperative voice therapy is mandatory at least until
inflammatory processes are over. The maximum benefit is
not apparent until 45 months postoperatively [129].
Although complete restoration with a clear and sonorous
voice may not be achieved, surgery does improve glottic
closure reducing the air loss and increasing the loudness
and vocal endurance. Most of these patients feel an
improvement due to decreased voice fatigue and dysthesia
in the throat and an increased voice intensity. Although
improvement of glottic closure can be considered a realistic
goal addressing rigidity by restoration of a new SLP is one
of the future issues in phonosurgery. New developments
include the treatment with softening angiolytic lasers,
ultrafine excisional laser and especially, techniques of tissue engineering including injection of various growth
factors, stem cells or implanting scaffolds. Despite the
promising results by in vitro experiments, animal studies
123
and first clinical trials, the step into routine clinical application has yet to be done.
The literature dealing with treatment of VF scars is often
based on personal experience and there is a strong need for
prospective studies. One example in this regard is a work
published by Welham et al. [130]. In this multi-arm evaluation, they compared clinical effectiveness of type I thyroplasty, injection laryngoplasty, and graft implantation
(fascia). Despite significant improvements in all groups, he
concluded that no single treatment modality is successful
for the majority of patients and that there is a need for the
identification of predictive clinical features that can drive
an evidence-based treatment assignment.
Acknowledgments The authors would like to acknowledge Claus
Gerstenberger, PhD for his contribution in all graphic-design related
works.
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