Annals of Otology, Rhinology & Laryngology 118(9):613-620.

© 2009 Annals Publishing Company. All rights reserved.

Implantation of an Atelocollagen Sheet for the Treatment of

Vocal Fold Scarring and Sulcus Vocalis
Yo Kishimoto, MD; Shigeru Hirano, MD, PhD; Tsuyoshi Kojima, MD;
Shin-ichi Kanemaru, MD, PhD; Juichi Ito, MD, PhD

Objectives: The management of vocal fold scarring and sulcus vocalis is challenging. These disorders are thought to be
fibroplastic anomalies in the cover portion of the vocal fold that cause deterioration of the vibratory properties of the vo-
cal fold mucosa. Histologic studies have revealed disorganization of extracellular matrix that needs to be addressed in the
treatment of scarred vocal folds. Replacement of scar tissues with an appropriate implant may lead to regeneration of the
vocal fold mucosa and its tissue properties. This retrospective case study examined the feasibility of using an atelocol-
lagen sheet as a regenerative implant.
Methods: Six patients with a post-cordectomy scar or sulcus vocalis underwent implantation of an atelocollagen sheet
into the lamina propria of the vocal folds. The procedure consisted of elevation of a microflap, dissection and removal
of scar tissue, implantation of the material, and wound closure. Vocal function was evaluated before and after surgery by
stroboscopic examination and by aerodynamic and acoustic analyses.
Results: The postoperative changes of aerodynamic and acoustic parameters varied among patients; however, gradual
improvement was seen in most cases over a year. Stroboscopic findings also revealed gradual improvement of vibratory
properties in most cases.
Conclusions: Implantation of an atelocollagen sheet may have restorative effects on vocal fold scarring and sulcus vo-
calis in terms of tissue properties and function of the mucosa.
Key Words: atelocollagen sheet, human, sulcus vocalis, vocal fold scarring.

INTRODUCTION sulcus vocalis,1,2 and development of new regenera-

tive strategies is being pursued.
The management of vocal fold scarring and sul-
cus vocalis remains a therapeutic challenge.1 Vocal In tissue engineering, regeneration of tissues or
fold scarring occurs after injury and inflammation. organs can be achieved by a combination of scaf-
It disrupts the layer structure of the lamina propria, fold, cell, and regulatory factors under appropri-
changing the biomechanical properties of the vo- ate conditions. According to this concept, we have
cal fold. Sulcus vocalis is a migration of the vocal tried to regenerate injured vocal folds using autolo-
fold epithelium into the normally convex superficial gous mesenchymal stem cells and growth factors.5,6
lamina propria or deeper layers.2 Both of these con- Although we have shown the effectiveness of cell
ditions result in intractable dysphonia and glottal in- therapy5 and growth factor therapy6 in the treatment
sufficiency. Because previous histologic studies3,4 of vocal fold scarring using animal models, there
revealed similar disorganization of extracellular ma- are still some problems for clinical use. Moreover,
trix components in both conditions, it is thought that an appropriate scaffold is usually needed to obtain
strategies for treatment of vocal fold scarring and ideal regenerative effects of cells and growth factors
sulcus vocalis could be the same. inside the vocal fold.
For vocal fold scarring and sulcus vocalis, various Atelocollagen sheeting (Terudermis, Olympus Ter­-
kinds of therapeutic strategies, such as voice therapy umo Biomaterials Corp, Tokyo, Japan) is a cross-
or pharmacologic and surgical treatment, have been linked collagen material with abundant micropores
attempted to soften the scarred tissues or to restore that can recruit cells from surrounding tissues. It is
its normal properties. However, to date there is no biocompatible and biodegradable, and has been used
optimal strategy to restore the scarred vocal fold or for coverage and dressing of postsurgical dermal or
From the Department of Otolaryngology–Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Presented at the meeting of the American Broncho-Esophagological Association, Phoenix, Arizona, May 28-29, 2009.
Correspondence: Shigeru Hirano, MD, PhD, Dept of Otolaryngology–Head and Neck Surgery, Kyoto University Graduate School of
Medicine, Sakyo-ku, Kyoto 606-8507, Japan.

613

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614 Kishimoto et al, Implantation of Atelocollagen Sheet 614

PATIENT DATA
Side
Age Initial Additional Closing Follow-Up
Case Sex (y) Diagnosis Implant Implant Method (mo)
1 M 68 Post-cordectomy scar R Polydioxanone suture 32
R Polydioxanone suture 18.5
2 F 40 Rheumatoid arthritis and post–superficial L Polydioxanone suture 24
cordotomy scar
R Polydioxanone suture 7
3 M 56 Sulcus vocalis Bilateral Fibrin glue 8
4 F 40 Sulcus vocalis L Fibrin glue 17
5 M 60 Post-cordectomy scar L Polydioxanone suture 6
6 F 50 Sulcus vocalis Bilateral Fibrin glue 17

epidermal defects in several parts of the body to stim-
ulate wound healing.7,8 Since 2005, we have treated
patients with vocal fold scarring or sulcus vocalis
with implants of the atelocollagen sheet because of
its regenerative characteristics. In this study, we ex-
amined the feasibility of the atelocollagen sheet as a
regenerative scaffold in the treatment of vocal fold
scarring and sulcus vocalis.
MATERIALS AND METHODS
Patients. The clinical information about patients
and surgical procedures is summarized in the Table.
Six adult patients (3 men and 3 women), 3 with post-
cordectomy scarring and 3 with sulcus vocalis, were
treated with an implant of Terudermis into the vocal
fold during 2006 and 2007 at Kyoto University Hos-
pital. Inclusion criteria were sulcus vocalis or vocal
fold scarring accompanied by hoarseness. The pro-
cedure was carried out with the patient’s agreement.
Their ages ranged from 40 to 68 years (average,
52.3 years), and the postoperative follow-up period
varied from 6 to 32 months. The implants were per-
formed on one side of the vocal fold or both, accord-
ing to the site and/or severity of the lesion. Four pa-
tients were treated with a unilateral implant in their
initial surgeries, and 2 of these later received an ad-
ditional implant because the effect of the unilateral
implant was limited. Another 2 patients (cases 3 and
6) received simultaneous bilateral implants.
Preparation of Terudermis. Terudermis is made
by cross-linking atelocollagens derived from bovine
skin tissues. The possibility of mad cow disease

A B

Fig 1. (Case 5) Implantation of

atelocollagen sheet into left vo-
cal fold. A) Incision on superior
surface of vocal fold. B) Subepi-
thelial pocket. C) Atelocollagen
C D sheet implanted into pocket. D)
Polydioxanone suture was used
to close pocket.

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615 Kishimoto et al, Implantation of Atelocollagen Sheet 615
Fig 2. Concept of Terudermis implant.
caused by this material was excluded. The thick-
ness of this material is 3 mm, and it contains abun-
dant micropores, 50 to 500 μm in diameter, that are
thought to be suitable for the influx of cells into the
sheet. Indeed, it was confirmed that implanted Teru-
dermis recruited cells from the surrounding tissues
in animal experiments.9 In addition, the material
is tolerant to collagenase, and it was confirmed in
rat models that the material remained undamaged 4
weeks after implantation.9 Terudermis is allowed for
use in human patients with any dermal or epidermal
defects of the skin or mucosal tissues by the Minis-
try of Health, Labor, and Welfare in Japan.
Surgical Procedure. The procedure consisted of
elevation of a microflap, dissection and removal of
underlying scar tissues, implantation of Terudermis,
and wound closure. The glottis was exposed with
either a Zeitels Universal Modular Glottiscope (En-
docraft LLC, Winter Park, Florida) or a Kleinsasser
Laryngoscope (Karl Storz GmbH & Co, Tuttlingen,
Germany) under general anesthesia.
After hydrodissection was performed by subepi­
thelial injection of 1:80,000 epinephrine, the free
edge of the vocal fold was grasped with micro-
A B
Fig 3. In most cases, gradual improvement is shown by A) normalized mucosal wave amplitude and B) normalized glottal gap.
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forceps and retracted medially. A vertical incision
along the longitudinal axis of the vocal fold was
made lateral to the scarred site or sulcus on the su-
perior surface of the vocal fold (Fig 1A). Underly-
ing scar tissue was dissected with a microdissector,
and removed when necessary (Fig 1B). Finally, a
subepithelial pocket was made between the epithe-
lium and the vocal ligament in which Terudermis
was to be implanted. Terudermis was cut to a suit-
able size and then inserted into the pocket (Fig 1C).
After implantation of the sheet, the microflap was
put back into its original position. A polydioxanone
suture or fibrin glue was used to close the pocket to
prevent loss or dislocation of the implanted material
(Fig 1D).
Figure 2 illustrates the concept of this procedure.
It was expected that cells, and possibly growth fac-
tors, might migrate into the implanted sheet of Teru-
dermis.
Assessment. Two trained laryngologists made
blind measurements. The assessment consisted of
stroboscopic, acoustic, and aerodynamic examina-
tions. The voice and stroboscopic samples were re-
corded at normal pitch and normal loudness for 3
times at each evaluation. Stroboscopic examinations
were performed with a Digital Video Stroboscopy
System model 9295 (KayPENTAX, Lincoln Park,
New Jersey) to assess temporal changes of the mu-
cosal wave and glottic closure. The amplitude of the
mucosal wave and the glottal gap were examined
with image analysis software (Scion Image beta3b,
Frederick, Massachusetts). The distance (d1) from
the midline of the glottis to the free edge of the vo-
cal fold was measured at the anteroposterior middle
portion of the vocal fold during the closed phase,
and then the same distance (d2) was measured at the
maximum open phase.
The mucosal wave amplitude was normalized by
the distance (L) from the anterior commissure to the
vocal process. The normalized mucosal wave am-
616 Kishimoto et al, Implantation of Atelocollagen Sheet 616
A B
C D
plitude (NMWA) was calculated from the formula
NMWA = (d2 – d1)/L. This measurement was done
on the treated side of the vocal fold. The glottal
gap was examined on the images during the closed
phase. The glottal area (a) was measured, and the
normalized glottal gap (NGG) was calculated as
NGG = a/L2.
The aerodynamic and acoustic examinations were
completed at the same time points. Aerodynamic
examinations included maximum phonation time
and mean flow rate. The Computerized Speech Lab
(KayPENTAX) was used to evaluate the pitch per-
turbation quotient, amplitude perturbation quotient,
and noise-to-harmonics ratio.
RESULTS
Vibratory Examination. Figure 3 shows the tem-
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Fig 4. Aerodynamic and acoustic parameters showed gradual
improvements in most cases. A) Maximum phonation time. B)
Mean flow rate. C) Pitch perturbation quotient. D) Amplitude
perturbation quotient. E) Noise-to-harmonics ratio.
poral changes of the NMWA and NGG. The NMWA
showed gradual improvement in all cases except
case 3, and the NGG became smaller with time in
4 of 6 cases.
Aerodynamic and Acoustic Examinations. Aero-
dynamic and acoustic parameters had individual
variations, but generally the maximum phonation
time, mean flow rate, pitch perturbation quotient,
amplitude perturbation quotient, and noise-to-har-
monics ratio showed gradual improvement in most
cases over 1 year (Fig 4).
Representative Cases. In case 1, a 68-year-old
man had scarring after undergoing laser cordectomy
for glottic carcinoma. The vibration of the right vo-
cal fold was limited, and incomplete glottal closure
was observed (Fig 5A). Terudermis was initially im-
planted into the right vocal fold. However, because
617 Kishimoto et al, Implantation of Atelocollagen Sheet 617

Fig 5. (Case 1) Stroboscopic findings. A) Before treatment. B) After treatment, vibration of right vocal fold is improved, and
almost complete glottal closure is observed.
the vibration of the vocal fold was still limited, with
incomplete glottal closure at the posterior portion
of the glottis, a second implant was placed in the
posterior portion of the right vocal fold. The glot-
tal closure and vibration of the vocal fold gradually
improved over 7 months after the second operation
(Fig 5B).
In case 2, a 40-year-old woman had an idiopathic
scar that was possibly due to rheumatoid arthritis in
the vocal fold. She had undergone superficial cordo-
tomy by another surgeon to remove the scar tissue.
Her postoperative voice had not improved 3 months
after the cordotomy, and she was referred to us. On
the first visit, she was nearly aphonic and there was
no mucosal vibration on stroboscopic examination
(Fig 6A). We resected as much scar tissue as pos-
sible beneath the epithelium and implanted Teruder-
mis into the left vocal fold. Figure 6B shows strobo-
scopic findings made 24 months after the implanta-
tion that indicate the appearance of mucosal vibra-
tion.
In case 4, a 40-year-old woman with left sulcus
vocalis was referred to us. Stroboscopic examina-
tion found no vibration of the vocal fold and a large
glottal gap (Fig 7A). Undermining of the sulcus was
initially done, and fibrous tissues were removed.
However, 3 months after the surgery, her voice had
not improved. In subsequent revision surgery, we
resected scarred tissues beneath the epithelium and
implanted Terudermis into the left vocal fold. After
the implantation, acoustic and stroboscopic exam-
ination revealed gradual improvement. Seventeen
months after the implantation, stroboscopic exami-
nation revealed improved mucosal wave vibration
(Fig 7B).
DISCUSSION
Various surgical approaches for the treatment of
vocal fold scarring and sulcus vocalis — medial-
ization thyroplasty, collagen or fat injection, exci-
sion of scar, and lysis of adhesions — have been
attempted to restore normal vocal fold properties.1,2
Medialization thyroplasty and collagen or fat injec-
tion result in augmentation effects, which improve

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618 Kishimoto et al, Implantation of Atelocollagen Sheet 618

Fig 6. (Case 2) Stroboscopic findings. A) Before treatment. B) Mucosal vibration appears in bilateral vocal folds after treat-
ment.

the glottal insufficiency and facilitate entrainment
of vocal fold oscillation. However, their effects are
limited, because restoration of the normal properties
of the vocal fold cannot be achieved by these meth-
ods. In addition, the effects of excision of scar or ly-
sis of adhesions depend on the individual’s healing
ability, and stable outcomes cannot be achieved with
this approach. Thus, in order to consistently restore
the normal properties of the vocal fold, a new regen-
erative strategy is needed.
In tissue engineering to regenerate tissues or or-
gans, it is necessary to combine a scaffold, cells, and
regulatory factors under appropriate conditions. In
general, a regenerative scaffold should have bio-
compatibility and biodegradability, provide appro-
priate space for regeneration, and have an appropri-
ate environment for cells to grow and work. Also,
the viability and function of cells that infiltrate into
the scaffolds should be maintained.
As a candidate for a regenerative scaffold, we
have focused on atelocollagen sheeting (Teruder-
mis). The sheeting used in this study is composed
of dehydrothermally cross-linked fibrillar atelocol-
lagen and heat-denatured atelocollagen.9,10 Because
of this structure, the material remains in the implant-
ed site for a long time, is infiltrated easily by cells
from surrounding tissues, and is thought to be an
ideal regenerative scaffold because it achieves ac-
ceptance in the early period after implantation that
results in long-term survival and little contracture.
In the vocal fold, it is expected that the implanted
material provides an appropriate space and environ-
ment for vocal fold fibroblasts to produce extracel-
lular matrix components and thus to restore scarred
tissues.
Similar approaches have been reported in an at-
tempt to treat sulcus vocalis. Tsunoda et al11-14 re-
ported that implantation of temporal fascia into the
vocal fold resulted in gradual improvements of max-
imum phonation time. Unpublished data also sug-
gested that Alloderm implanted into the Reinke’s
space of the sulcus might improve acoustic and stro-
boscopic parameters.2 However, how those materi-
als work in the vocal fold is still unclear. One of the

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619 Kishimoto et al, Implantation of Atelocollagen Sheet 619
Fig 7. (Case 4) Stroboscopic findings. A) Before treatment. B) After treatment, mucosal vibration shows improvement.
biggest advantages of Terudermis was thought to be
the porous structure of the sheet that can admit cells,
as already shown in previous animal studies.
In most cases in this study, aerodynamic and
acoustic analyses showed gradual improvement in
all parameters over 1 year, with individual variation,
and restoration of periodic vibration was also ob-
served by videostroboscopy. These results suggest
that the atelocollagen sheet implant has not only an
augmentative effect, but also a possible restorative
effect. Thus, implantation of the atelocollagen sheet
into the vocal fold may have therapeutic potential in
cases of vocal fold scarring and sulcus vocalis.
In case 3 only, most parameters worsened with
the implantation of Terudermis. It is conceivable
that the implanted material was lost or dislocated.
In this case, fibrin glue was used to close the pocket.
However, the actual reason for failure of improve-
ment is uncertain. Furthermore, it is likely that the
effect of an implant may be influenced by individual
healing ability.
It is impossible to use randomized controls in this
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kind of study. Also, it is difficult to confirm the re-
cruitment of cells into the material, because histo-
logic evaluation cannot be achieved in this kind of
study. We do not insist that our scaffold has a defi­
nite regenerative effect. The augmentative effects
may overlap; however, we believe that some of the
effects of the material are regenerative. The current
study has only shown the possibility of Terudermis
as a regenerative scaffold. Further study is neces-
sary to better understand the material and also to de-
velop better surgical procedures.
CONCLUSIONS
The current study examined the feasibility of an
atelocollagen sheet (Terudermis) implant for treat-
ment of scarred vocal folds or sulcus vocalis. Six
patients underwent implantation into the stiffened
vocal folds. In most cases, videostroboscopic ex-
amination and aerodynamic and acoustic analyses
showed gradual improvement over 1 year after sur-
gery. The results suggest that implantation of Teru­
dermis may have restorative effects in cases of vocal
fold scarring and sulcus vocalis.
620 Kishimoto et al, Implantation of Atelocollagen Sheet 620
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