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Soft Tissue Augmentation Techniques and

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Article in Implant Dentistry · February 2016

DOI: 10.1097/ID.0000000000000385

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WOLFF ET AL IMPLANT DENTISTRY / VOLUME 25, NUMBER 3 2016 1

Soft Tissue Augmentation Techniques

and Materials Used in the Oral Cavity:
An Overview
Jan Wolff, DDS, Dr Med Dent,* Elisabet Farré-Guasch, DDS, PhD,† George K. Sándor, MD, DDS, PhD,‡
Susan Gibbs, PhD,§ Derk Jan Jager, DMD, PhD,¶ and Tymour Forouzanfar, DDS, MD, PhDk

he oral mucosa typically com- Purpose: Oral soft tissue aug- a large variety of materials and

T prises a shiny red alveolar

mucosa and a coral pink masti-
catory mucosa.1 The nonattached alve-
mentation or grafting procedures
are often necessary to achieve
proper wound closure after deficits
techniques, including grafts, local
flaps, allogenic derived matrices
such as acellular dermal allograft,
olar mucosa is thin and is mostly resulting from tumor excision, clefts, xenogenic tissue matrices from ani-
composed of loosely affiliated colla-
trauma, dental implants, and tooth mal origin, and synthetic materials.
gen fibers. In contrast, the attached
mucosa is fixed, thick, keratinized, recessions. Conclusions: Tissue engineer-
and is composed of well-organized, Materials and Methods: Autol- ing of oral mucosa represents an
dense, collagen fibers. Being firm, ogous soft tissue grafts still remain interesting alternative to obtain suf-
stippled, and tightly attached to the the gold standard to acquire a func- ficient autologous tissue for recon-
periosteum, the masticatory mucosa tionally adequate zone of keratinized structing oral wounds using
can resist physical, thermal, and chem- attached gingiva. However, soft tis- biodegradable scaffolds, and may
ical insults.2 sue substitutes are more commonly improve vascularization and epithe-
An adequate amount of attached used because they minimize morbid- lialization, which are critical for
keratinized tissue is instrumental for the ity and shorten surgical time. successful outcomes. (Implant Dent
maintenance of teeth, periodontal Results: This review aimed to 2016;25:1–8)
assess soft tissue grafting techniques Key Words: soft tissue, graft materi-
*Assistant Professor, Department of Oral and Maxillofacial
Surgery, VU University Medical Center/Academic Centre for and materials used in the oral cavity als, oral, matrix, scaffolds, tissue
Dentistry Amsterdam (ACTA), MOVE Research Institute
Amsterdam, Amsterdam, The Netherlands. from existing literature. There are engineering
†Postdoctoral Researcher, Department of Oral Cell Biology,
Academic Centre for Dentistry Amsterdam (ACTA), MOVE
Research Institute Amsterdam, University of Amsterdam and VU
University Amsterdam, Amsterdam, The Netherlands.
‡Professor, Department of Oral and Maxillofacial Surgery, Oulu
University Hospital, Medical Research Center, University of Oulu,
Oulu, Finland.
§Head Professor, Department of Oral Cell Biology, Academic
Centre for Dentistry Amsterdam (ACTA), MOVE Research
ligaments, and dental implants.3 Addi- buccal fat pad grafts. However, such
Institute Amsterdam, University of Amsterdam and VU University
Amsterdam, Amsterdam, The Netherlands; Professor of Skin
tionally, removable prosthetic devices augmentation techniques do have cer-
and Mucosa Regenerative Medicine, Head of Dermatology Lab, require zones of adequate attached ker- tain shortcomings, including morbidity,
Department of Dermatology, VU University Medical Centre,
Amsterdam, The Netherlands. atinized tissue to create a vacuum necrosis of the transplanted mucosa, and
¶Postdoctoral Researcher, Department of Oral and Maxillofacial
Surgery, VU University Medical Center/Academic Centre for between the mucosa and the denture poor color integration at the recipient
Dentistry Amsterdam (ACTA), MOVE Research Institute
Amsterdam, Amsterdam, The Netherlands. base to enable proper retention.4 How- site.7,8 These shortcomings have led to
kHead Professor, Department of Oral and Maxillofacial Surgery,
VU University Medical Center/Academic Centre for Dentistry ever, some patients lack a sufficient the development and use of alternative
Amsterdam (ACTA), MOVE Research Institute Amsterdam,
Amsterdam, The Netherlands. amount of soft tissue in their oral cavity augmentation materials. Such alterna-
mainly due to gingival recessions, in- tive products can be broadly divided into
Reprint requests and correspondence to: George K. fections, trauma, and tumors, and there- different groups according to their ori-
Sándor, MD, DDS, PhD, Department of Oral and
Maxillofacial Surgery, University of Oulu, Aapistie 5, fore, often require concomitant soft gin: allogeneic, xenogeneic, and syn-
90014 Oulu, Finland, Phone: +358 504280906, Fax: tissue reconstruction.5 thetic (alloplastic) materials (Table 1).
+358-537-5560, E-mail: george.sandor@oulu.fi
To date, a variety of autogenous Furthermore, a few new tissue-
ISSN 1056-6163/16/02503-001 augmentation techniques have been engineered constructs for soft tissue
Implant Dentistry
Volume 25  Number 3 described6 and can broadly be divided augmentation are being developed in
Copyright © 2016 Wolters Kluwer Health, Inc. All rights
reserved. into 3 major groups: free gingival grafts research settings; hence phase I and
DOI: 10.1097/ID.0000000000000385 (FGG), free buccal mucosa grafts, and case studies.10,39

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
2 SOFT TISSUE AUGMENTATION TECHNIQUES
Table 1. Commercially Available Grafts Commonly Used for Soft Tissue
Reconstruction
Generic Name
Alloderm9
AS21010
Matrix HD11
Epiflex12–14
Puros Dermis Allograft
Tissue Matrix6,15–17
Mucograft18–21
Polycaprolactone-based
polyurethaneurea
product, Artelon19,22–27
Self-inflating hydrogel
tissue expander28–38
Origin and resorption capacity of the different graft materials is specified. These materials can be classified according to their origin.
Allogeneic (Dermal Matrix), Xenogeneic (Animal), and Synthetic (Alloplastic) materials are mostly used for soft tissue reconstruction.
The aim of this study is to give an
overview of different soft tissue aug-
mentation techniques and materials
used for soft tissue augmentation in
the oral cavity. Furthermore, ongoing
research developments in the field of
tissue engineering will be discussed.
Autogenous Soft Tissue
Free gingival grafts. Free gingival
grafting is the most widely used oral
graft procedure to augment keratinized
tissue without root coverage.40 This
procedure is mainly used to achieve
a functionally adequate zone of kerati-
nized, hence “attached” gingiva in the
oral cavity. The most common condi-
tions treated with FGG are shallow ves-
tibule, periodontal pockets beyond the
mucogingival line, inadequate amount
of attached gingiva, frenum-related
gingival pull, and localized gingival re-
cessions.41 A major advantage of this
technique is that it can be performed
on a single or a group of teeth with high
predictability. However, harvesting
FGG has its drawbacks namely second-
ary donor site surgery, extended operat-
ing time, color and texture mismatch
between tissues, and limitation in the
amounts of available graft material.42
Furthermore, FGG are commonly har-
vested from the palate and subsequently
healed by secondary intention. This
healing process can take up to 4 weeks
Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Resorbable
Company Origin
AlloDerm Regenerative Tissue Allogen
Matrix, LifeCell
A-Skin BV Allogen
RTI Biologics, Inc. Allogen
German Institute for Cell Allogen
and Tissue Replacement,
Berlin, Germany
Zimmer Dental Allogen
Geistlich Porcine
Artimplant Synthetic
Cylinder Dental, Osmed GmbH Synthetic
and involves significant patient morbid-
ity.42 The lack of predictability in
achieving total root coverage and the
compromised blood supply must also
be considered as drawbacks of this
technique.43
One novel technique of circumvent-
ing the limitations of donor graft mate-
rial available in the palate is by using
self-inflating soft tissue expanders
(Cylinder Dental; Osmed GmbH,
Ilmenau, Germany), which offer enough
de novo soft tissue for vertical bone aug-
mentations and cause a minimal amount
of complications.28 These self-inflating
soft tissue expanders consist of an
osmotic active hydrogel, a methylmetha-
crylate and vinyl pyrrolidone, which
offer the possibility of controlling the
expansion speed and/or the end volume
of expansion.44 However, such expand-
ers require 6 to 8 weeks for full tissue
expansion.29 Clinical case studies have
demonstrated that self-inflating tissue
expanders can be successfully used for
the augmentation of atrophic alveolar
ridges thereby enabling tension free clo-
sure of the primary wound after bone
grafting.30–33 Furthermore, soft tissue
expanders have been successfully used
to treat difficult anterior palatal fistulas,34
cleft palate patients,35 congenital nasal
hypoplasia patients,36 scalp reconstruc-
tions, and congenital nevi reconstruc-
tions.37 Unlike conventional tissue
expanders, self-inflating hydrogel tissue
WOLFF ET AL
expanders do not need to be filled from
an external source and have rather good
mechanical properties. They can be
manufactured in almost any size and
Capacity shape and do not cause inflammatory
+ reactions.29,33
Free buccal mucosa grafts. Free buc-
+ cal mucosa grafts are commonly har-
+ vested from the lip or inner cheek.8 In
+
the past decades, surgeons have used
this technique for preprosthetic surgery,
+
after tumor ablation,45 for the closure of
defects of the tongue and the cheek,46 or
+ for the reconstruction of the conjunctiva
+ and the eyelid.47 Such grafts have been
successful and predictable, but there is
a limitation in the amount of autoge-
− nous tissue available from any given
individual.
Buccal fat pad grafts. The buccal fat
pad (BFP), both as a flap and as a free
graft, was originally used for the closure
of small to medium-sized oroantral
and oronasal communications.48–53
Recently, buccal fat pad grafts have
been used for a wide variety of surgical
procedures such as supporting bone
graft augmentations,54 sinus floor pro-
cedures,55 and to provide root coverage
for teeth with severe recessions.56,57
The use of BFP graft is becoming
increasingly popular because of its reli-
ability, ease of harvesting, and low
complication rate.58 Furthermore, BFP
grafts have shown to be a rich source of
stem cells which can be used for clinical
applications, and hence tissue
engineering.59
Although autografts still remain the
golden standard,60,61 they do have some
disadvantages, including an additional
harvest site with its associated pain and
morbidity and, sometimes, poor quality
and limited amount of graft material.18
To overcome these problems, a large
amount of alternative materials for soft
tissue augmentation are being used and
developed to date.
Allogenic Materials
Compared with autogenous grafts,
allografts are readily available. Allo-
genic human acellular dermis is com-
monly used in reconstructive and
general surgery for the treatment of
burns,62–64 breast reconstruction,62,65,66
and other indications such as abdominal
wall reconstruction, ventral hernia
WOLFF ET AL IMPLANT DENTISTRY / VOLUME 25, NUMBER 3 2016 3

repair, and intestinal elongation62,67,68 Matrix HD (RTI Biologics, Inc., gingival recessions in the maxilla.6,15
(Fig. 1). Allogenic acellular dermal Alachua, FL) is an acellular human Furthermore, it has been applied in the
matrix has been used for soft tissue dermis processed using a sterilization treatment of stress urinary inconti-
reconstruction before bone grafting to process that preserves the collagen nence.16 The dermal graft is processed
reduce the risk of exposure and failure structure. The dermis is a collagenous using a patented aseptic technique
of the bone graft.69 Several allogenic ma- connective tissue with 3-dimensional (Tutogen Medical, Alcoa, FL).15 The
terials or allografts have been described intertwined fibers that retain the multi- proprietary Tutoplast Process assures
for soft tissue augmentation. Allogenic directional and mechanical properties a high standard of tissue safety and
acellular dermis Alloderm (AlloDerm of native dermis. It supports natural quality with minimal risk of disease
Regenerative Tissue Matrix; LifeCell tissue architecture, cellular revascular- transmission.17 Puros Dermis is bio-
Corporation, Bridgewater, NJ) is the ization and repopulation by the host compatible and absorbable and assimi-
most widely described dermal matrix.9 tissue, preserves key components of the lates into the body’s normal tissue
Several clinical cases using acellular der- matrix, is biocompatible and safe, and is healing process.6,15
mal allografts to increase and restore the well suited for soft tissue reconstructive AS210 (A-SkinBV, Amsterdam,
width of attached gingiva have been re- surgical applications.11 The Netherlands) is an acellular dermal
ported.70 Furthermore, it has also been Epiflex is another product har- matrix which has been successfully used
used to treat oral mucosal defects result- vested from deceased human tissue to prepare chronic ulcer wound beds
ing from tumors, trauma, oral mucosal donors and is commonly used for the before applying an autologous skin sub-
diseases, and preprosthetic surgery.71 reconstruction of deep soft tissue de- stitute, and is also the dermal matrix for
Dermal matrix grafting procedures have fects after severe trauma or resection of tissue-engineered skin and oral mucosa
distinct advantages over autografts soft tissue sarcomas.12,13 substitutes (see below).10,39
because they do not cause donor site Puros Dermis Allograft Tissue
morbidity. Furthermore, clinical studies Matrix (Zimmer Dental, Carlsbad, Xenogenic Materials
have reported comparable, and in some CA) is an acellular dermal matrix which Xenogenic-derived matrices com-
cases, superior clinical results than those has been successfully used for the monly used for oral soft tissue augmen-
attained with autogenous palatal tissue correction of iatrogenic gingival reces- tation are of porcine, bovine, or equine
grafts.6 Unlike other acellular human sions in the esthetic zone, increasing origin.18,19,72–77 Xenogenic porcine col-
dermis products, AlloDerm Tissue the height and width of the zone of lagen matrices have been described as
Matrix is produced using a nondamaging keratinized tissue, and providing good being comparable to autogenous soft
manufacturing process that allows the soft tissue integration and tissue color tissue constructs.18 Porcine acellular
body to mount its own tissue regenera- matching. It has also been successfully dermal matrix can act as a biodegrad-
tion process.9 used for correction of deep-wide able scaffold for the delivery of cells,
and furthermore preserve space for
new periodontal tissue formation,
which is a paramount for successful
periodontal tissue regeneration.78,79
A bioactive scaffold composed of
a native 3D collagen framework, puri-
fied from porcine acellular dermal
matrix (PADM), and further treated
with hydroxyapatite (HA) to promote
bioactivity and cell differentiation, was
evaluated in terms of biocompatibility
in vitro and in vivo.80 The study proved
that HA-PADM scaffolds had good
biocompatibility in animals in vivo
and appropriate biodegrading charac-
teristics in vitro using human periodon-
tal ligament cells, which were able to
proliferate and migrate into the scaf-
Fig. 1. Photomicrographs showing the immunohistochemistry staining comparison of human fold. These observations suggest that
skin, and 2 types of acellular donor dermis available for transplantation, AS210 and AlloDerm. HA-PADM scaffolds can be used as
This characterization shows staining of the basement membrane proteins with collagen IV and cell carriers for periodontal tissue
laminin along with the presence of cell remnants stained with antibodies against major histo-
regeneration.
compatibility (MHC) Class I antigens (HLA-ABC) and MHC Class II (HLA-DR). There is retention
of the basement membrane proteins and cell remnants in all 3 of the dermal matrices. The lack Recently several xenogenic mate-
of human leucocyte antigen (HLA) staining of the acellular dermis makes it usable for allogenic rials have become more readily avail-
transplantation to other individuals. able on the market. The product with the
most scientific literature is the 2-layer

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
4 SOFT TISSUE AUGMENTATION TECHNIQUES
porcine collagen matrix (Mucograft;
Geistlich organic material, Wolhusen,
Switzerland).18–21
Nevins et al19 demonstrated that
Mucograft increases the amount of
attached, keratinized gingiva signifi-
cantly in vivo. Vignoletti et al21 reported
that Mucograft had a positive effect on
wound healing of attached, keratinized
gingiva and can be considered as a safe
and effective method of treating gingi-
val recessions.
Mucoderm (Botiss Dental Berlin,
Berlin, Germany) is a collagen tissue
matrix derived from animal dermis and
passes through a multi-step cleaning
process which removes all potential
tissue rejection components from the
dermis. This results in a 3-dimensional
stable matrix consisting of collagen and
elastin. After placement, the patient’s
blood infiltrates into the Mucoderm
graft, bringing host cells to the soft tis-
sue graft surface triggering the revascu-
larization process. Mucoderm has been
used for the treatment of oral dehis-
cence, ridge preservation, root cover-
age, sinus floor elevations, and vertical
augmentations.74
Synthetic (Alloplastic) Materials
Synthetic (alloplastic) materials
have also been used for soft tissue
augmentation in the oral cavity. For
more than a decade, a degradable poly-
caprolactone-based polyurethane urea
product produced by, Artelon (Artim-
plant, Stockholm, Sweden) has been
successfully used in orthopedic surgery
and oral soft tissue regeneration.22–25
Artelon has been used for buccal soft
tissue augmentation in connection with
oral implant treatment in the esthetic
zone of maxilla and has shown to
increase the mucosa volume at the
recipient site.26
This porous polyurethane urea
product acts as a scaffold that pro-
motes ingrowth of native human tis-
sue. Artelon is biocompatible and has
good mechanical properties and de-
grades slowly by hydrolysis, with
a degradation time of more than
4 years.81 Artelon has also been used
for resurfacing of joint surfaces (eg,
osteoarthritis, Hallux rigidus) and the
reinforcement and augmentation of
ligaments, tendons, and soft tissues.
Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Polyurethane has been found to be
one of the most successful polymers
for soft tissue applications.27 Never-
theless, Artelon to the best of our
knowledge has only been used in 1
study focusing on the soft tissue aug-
mentation of the anterior oral region.19
In this study, preoperative and postop-
erative casts were obtained and dem-
onstrated a significant increase in soft
tissue after 6 months.19
Tissue-Engineered Three-Dimensional
(3D) Full-Thickness Oral Mucosa
Over the years, advancements
have been made in the area of soft
tissue engineering. Such novel tech-
nologies have advantages because
they overcome the limitations of har-
vesting a large autograft. Much has
been learnt from skin tissue engineer-
ing. Already in the 1980s, cultured
epithelial sheets of human skin ob-
tained from a small biopsy were used
to close deep third degree burns thus
saving the life of the burns victim.82 A
similar method was used for culturing
oral epithelial cells for intraoral graft-
ing in the early 90s.83 However, the
aforementioned epithelial sheets have
certain drawbacks: they are extremely
fragile, often blister, and do not con-
tain connective tissue, and therefore
they are not suitable for full thickness
mucosa transplantations.
Natural scaffolds (collagen). To con-
struct a living connective tissue, a scaf-
fold is required which will support
growth of viable fibroblasts. Upon
transplantation, the scaffold will
degrade over time and replaced by
new extracellular matrix (ECM)
secreted by fibroblasts. Natural scaf-
folds composed of either cadaver or
animal derived de-epithelialized acel-
lular matrices or natural polymers
extracted from animals are being used
to date.73 In a randomized clinical
trial, cultured gingival grafts combined
with human gingival fibroblasts on
a biodegradable collagen scaffold
have shown to be a safe method of
generating keratinized attached gin-
gival tissue.84 The same group re-
ported successful application of
tissue-engineered gingival grafts pro-
duced by mixing collagen and human
WOLFF ET AL
gingival fibroblasts for regeneration
of attached keratinized gingiva.85
Synthetic and electrospun scaffolds.
As an alternative to the natural scaffold,
a number of synthetic scaffolds are to
date being developed. Again lessons are
being learnt from skin tissue engineer-
ing in which dermal substitutes have
been developed to close chronic
wounds, for example, leg and foot
ulcers. The most renowned dermal sub-
stitute is Dermagraft (Advanced Tissue
Sciences Inc., La Jolla, CA), which is
a dermal substitute composed of
a biodegradable polymer mesh with
cryopreserved (nonviable) allogeneic
dermal fibroblasts. The active compo-
nent of Dermagraft is the extensive
cocktail of cytokines and growth factors
produced by the fibroblasts before
cryopreservation. This construct has in
the past undergone extensive phase III
safety and efficacy testing for treating
diabetic foot ulcers.86 However, no
comparable construct is yet available
for oral mucosa and Dermagraft is no
longer commercially available.
More interesting are recent ad-
vancements in the field of electrospun
scaffolds that can support viable cell
growth.87 Electrospinning is a technique
that allows the production of ultrafine
fibers in nanometer or submicron range
by electrically charging a suspended
polymer droplet. Studies have shown
that nanoscale scaffolds are capable of
supporting different types of cells,
better than micron sized fibers.88,89 Fur-
thermore, such 3D scaffolds composed
of nanoscale multifibrils aim to mimic
the supramolecular architecture and the
biological functions of the natural
extracellular matrix. The presence of
such an ECM, constituted of proteins
and polysaccharides, is a key factor
in the healing and regeneration of soft
tissues. Moreover, the nano-fibrous fea-
ture of the ECM improves cell prolifer-
ation and addresses their phenotype.90
Furthermore, stem cells have shown
to proliferate and differentiate to kerati-
nocytes on a synthetic electrospun
scaffold.91
Full thickness oral mucosa substitutes.
The major limitation of the fibroblast-
populated scaffold is that the epithelium
is absent and therefore the construct is
WOLFF ET AL IMPLANT DENTISTRY / VOLUME 25, NUMBER 3 2016 5

only suitable for closing small lesions

where re-epithelialization takes place
from the wound margins. Ideally a full
thickness construct is required consist-
ing of a reconstructed differentiated
epithelium on a fibroblast-populated
connective tissue matrix.
Apligraf (Organogenesis, Canton,
MA) is a composite graft composed of
an “epidermal” layer of allogenic skin
keratinocytes grown on a “dermal”
layer of fibroblast-populated bovine
collagen gel.92,93 Production of cyto-
kines and growth factors by the tissue-
engineered skin can influence the host
cells and induce tissue regeneration and
remodeling, which offers an interesting
potential for treatment of small gingival
soft-tissue defects. Safety and efficacy
phase III studies have been performed
in diabetic foot ulcers and venous leg
ulcers.92,94 The most recent and
advanced development is an autologous
full thickness skin or oral mucosa con-
struct developed from 3-mm diameter
punch biopsies obtained from the
patient to be treated. The scaffold is
acellular donor dermis (AS210; A-Skin
BV, Amsterdam, The Netherlands). Pa-
tient’s own skin or oral derived fibro-
blasts are seeded into the dermis
scaffold, and epithelial cells are seeded
on top (Fig. 2). The one-step culture
procedure used ensures that the con-
struct is ready for transplantation within
3 weeks and that extremely little donor
tissue is required. The autologous skin
substitute has undergone extensive
phase I testing with more than 100 ther-
apy-resistant ulcers.10 Safety was con-
firmed and therefore the construct is
available under a hospital exemption
within The Netherlands, and a phase II
study is now underway. The oral
mucosa counterpart in the form of an
autologous gingiva substitute has
undergone proof of concept testing in
closing 3 gingiva lesions and is now
ready for more extensive phase I test-
ing.39 If successful, this construct will
provide a state of the art alternative to
the current gold standard autograft.
Importantly, first results indicate that it
has the potential to overcome the major
challenges faced in skin and oral sub-
stitutes which include mechanical prop-
erties, biocompatibility, structural
differentiation, optimal vascularization
Fig. 2. Photographs and photomicrographs comparing an autologous and a full thickness
gingival mucosal substitute constructed from two 3-mm diameter gingiva biopsies. The re-
constructed differentiated epithelium is on top of a fibroblast-populated acellular dermis. The
microscopic hematoxylin and eosin stained tissue shows sections of gingiva biopsy and the
gingiva substitute. The cultured gingiva substitute consists of a reconstructed differentiated epi-
thelium on a fibroblast-populated acellular dermis which closely represents native healthy gingiva.
(take rate), and good scar quality.10,39,95 compliant with the ATMPs regulations.
Future combinations with artificial or Tissue engineering, which involves cell
electrospun scaffolds will subsequently culture and amplification of human cells
replace the use of donor acellular der- ex vivo, has to be performed under Good
mis thus creating a totally autologous Manufacturing Practice with clinical
construct. grade culture medium components in
a cleanroom facility where extensive
European regulations for tissue- in-process and quality controls are incor-
engineered oral mucosa. Since 2006, porated to ensure patient safety.97
and before introduction of the recently For these reasons, no human oral
introduced strict European regulations tissue-engineered products for clinical
for Advanced Therapy Medicinal Prod- applications are yet commercially avail-
ucts (ATMPs), numerous studies re- able because laboratories are busy intro-
ported the use of 3D oral mucosal ducing these standards. However, it is
models with modified cell sources such expected that in the nearby future, clini-
as oral keratinocytes and fibroblasts, cal trials will be performed followed by
scaffolds, and culture media for pro- commercial production and wide-spread
duction of human oral mucosal compo- implementation. Novel tissue engineer-
sites, which offer promising applications ing techniques are developing rapidly
in studies on biocompatibility assess- and could offer an interesting alternative
ment of dental materials and oral health- to obtain sufficient autologous tissue for
care products, in treatment of ulcers or reconstructing oral mucosa using biode-
tooth extraction sites.39,86,92,94,96 Engi- gradable scaffolds.98,99
neering of full-thickness oral mucosa
overcomes the disadvantages of limited
availability and morbidity of autografts, SUMMARY AND CONCLUSIONS
considered the gold standard, but re- The reconstruction of oral soft
quires an ex-vivo process of production tissue with autografts or grafts obtained
that may take up to a month and must be from the same patient can be broadly

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
6 SOFT TISSUE AUGMENTATION TECHNIQUES
divided into 3 major groups: free gin-
gival grafts, free buccal mucosa grafts,
and buccal fat pad grafts. However,
many patients undergoing such treat-
ment often require large amounts of
tissue which cannot always be easily
harvested in the oral cavity; therefore,
new materials are being developed to
undermine the need of harvesting, that
is, from allogeneic, xenogeneic, and
synthetic origin or alloplastic materials.
Self-inflating soft tissue hydrogel
expanders have been successfully used
to acquire surplus amounts of soft tissue
to cover bone grafts. The major advan-
tages of such tissue expanders are their
high biocompatibility, low complica-
tion rates, nongenotoxic and nonimmu-
no reactivity, material pureness, and
safety which subsequently ensures
a low risk of infection. However, this
technique has some drawbacks, such as
patient discomfort during expansion
and waiting time of 6 to 10 weeks; and
a second surgery is required to remove
the expander and simultaneously per-
form a bone augmentation. Besides
this, only a limited amount of tissue
can be expanded in comparison to allo-
plastic materials that are readily
available.
Collagen matrix, which resembles
the extracellular matrix, has been
widely used for soft tissue augmenta-
tion. However, using collagen matrix
for periodontal regeneration has its own
disadvantages such as low mechanical
stiffness and rapid biodegradation. Fur-
thermore, such synthetic scaffolds lack
important ECM proteins. Therefore,
acellularized xenogenic tissues could
be a promising alternative material for
soft tissue regeneration because they
maintain their 3D structure and sub-
sequently offer good mechanical
properties.
The use of soft tissue substitutes for
augmentation purposes has increased
over the last few years, but still has not
made the commercial breakthrough
comparable to that of bone substitutes.
Nevertheless, recently, tissue-engi-
neered three-dimensional (3D) oral
mucosal grafts have been tested and
could offer a promising alternative to
conventional grafts. Furthermore, new
synthetic electrospun nanofibrous scaf-
folds have been introduced in skin
Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
tissue engineering and could in the
future also be used for oral tissue
engineering.
DISCLOSURE
S. Gibbs is co-founder of the
VUMC university spin off company
A-Skin BV.
The other authors claim to have no
financial interest, either directly or
indirectly, in the products or informa-
tion listed in the article.
J. Wolff and E. Farré-Guasch con-
tributed equally to this manuscript.
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