Anda di halaman 1dari 9


discussions, stats, and author profiles for this publication at:

Soft Tissue Augmentation Techniques and

Materials Used in the Oral Cavity

Article in Implant Dentistry · February 2016

DOI: 10.1097/ID.0000000000000385


0 443

6 authors, including:

Jan Wolff Elisabet Farre Guasch

VU University Medical Center VU University Amsterdam


George K Sándor Tymour Forouzanfar

University of Oulu VU University Medical Center


Some of the authors of this publication are also working on these related projects:

Treatment of craniosynostoses View project

All content following this page was uploaded by Jan Wolff on 08 February 2016.

The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document
and are linked to publications on ResearchGate, letting you access and read them immediately.

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:
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.

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

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

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-
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.

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

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

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

divided into 3 major groups: free gin- tissue engineering and could in the and hospitalized setting. Wound Repair
gival grafts, free buccal mucosa grafts, future also be used for oral tissue Regen. 2013;21:667–676.
and buccal fat pad grafts. However, engineering. 11. Faleris JA, Hernandez RM, Wetzel
D, et al. In-vivo and in-vitro histological
many patients undergoing such treat- evaluation of two commercially available
ment often require large amounts of
tissue which cannot always be easily DISCLOSURE acellular dermal matrices. Hernia. 2011;
harvested in the oral cavity; therefore, S. Gibbs is co-founder of the 12. Adamakis I, Tyritzis SI, Stravodimos
new materials are being developed to VUMC university spin off company KG, et al. A novel approach for the surgical
undermine the need of harvesting, that A-Skin BV. management of Peyronie’s disease using
is, from allogeneic, xenogeneic, and The other authors claim to have no an acellular, human dermis tissue graft:
Preliminary results. World J Urol. 2011;
synthetic origin or alloplastic materials. financial interest, either directly or 29:399–403.
Self-inflating soft tissue hydrogel indirectly, in the products or informa- 13. Rössner E, Smith MD, Petschke B,
expanders have been successfully used tion listed in the article. et al. Epiflex(Ò) a new decellularized
to acquire surplus amounts of soft tissue J. Wolff and E. Farré-Guasch con- human skin tissue transplant: Manufacture
to cover bone grafts. The major advan- tributed equally to this manuscript. and properties. Cell Tissue Bank. 2011;12:
tages of such tissue expanders are their 209–217.
high biocompatibility, low complica- 14. Roessner ED, Vitacolonna M,
tion rates, nongenotoxic and nonimmu- REFERENCES Hohenberger P. Confocal laser scanning
1. Katafuchi M, Matsuura T, microscopy evaluation of an acellular der-
no reactivity, material pureness, and mis tissue transplant (EpiflexÒ). PLoS One.
safety which subsequently ensures Atsawasuwan P, et al. Biochemical char-
acterization of collagen in alveolar mucosa 2012;7:e45991.
a low risk of infection. However, this 15. Petrungaro P. Correction of Iatro-
and attached gingiva of pig. Connect Tis-
technique has some drawbacks, such as sue Res. 2007;48:85–92. genic gingival recession in the esthetic
patient discomfort during expansion 2. Wennström JL, Bengazi F, Lekholm zone. Inside Dentistry. 2007;11:2–4.
and waiting time of 6 to 10 weeks; and U. The influence of the masticatory 16. Onur R. Singla a. Solvent-
a second surgery is required to remove mucosa on the peri-implant soft tissue dehydrated cadaveric dermis: A new allo-
condition. Clin Oral Implants Res. 1994;5: graft for pubovaginal sling surgery. J Urol.
the expander and simultaneously per- 2005;12:801–805.
form a bone augmentation. Besides 1–8.
3. Lee KH, Kim BO, Jang HS. Clinical 17. Schoepf C. Allograft safety: Effi-
this, only a limited amount of tissue evaluation of a collagen matrix to enhance cacy of the TutoplastÒ process. Int J Oral
can be expanded in comparison to allo- the width of keratinized gingiva around Implantol. 2006;7:10–15.
plastic materials that are readily dental implants. J Periodontal Implant 18. Herford AS, Akin L, Cicciu M, et al.
available. Sci. 2010;40:96–101. Use of a porcine collagen matrix as an
Collagen matrix, which resembles 4. Goldberg PV, Higginbottom FL, alternative to autogenous tissue for graft-
Wilson TG. Periodontal considerations in ing oral soft tissue defects. J Oral Maxillo-
the extracellular matrix, has been fac Surg. 2010;68:1463–1470.
widely used for soft tissue augmenta- restorative and implant therapy. Periodon-
tol 2000. 2001;25:100–109. 19. Nevins M, Nevins ML, Kim SW,
tion. However, using collagen matrix 5. Kao RT, Pasquinelli K. Thick vs. thin et al. The use of mucograft collagen matrix
for periodontal regeneration has its own gingival tissue: A key determinant in tissue to augment the amount of keratinized
disadvantages such as low mechanical response to disease and restorative treat- tissue around teeth: A pilot study. Int J
stiffness and rapid biodegradation. Fur- ment. J Calif Dent Assoc. 2002;30:521–526. Periodontics Restorative Dent. 2011;31:
thermore, such synthetic scaffolds lack 6. Petrungaro PS. Acellular dermal 367–373.
matrix tissue grafts. Inside Dentistry. 20. Sanz M, Lorenzo R, Aranda JJ,
important ECM proteins. Therefore, et al. Clinical evaluation of a new collagen
acellularized xenogenic tissues could 2010;6:2–9.
7. Hämmerle CHF, Jung RE. Ridge matrix (Mucograft prototype) to enhance
be a promising alternative material for augmentation procedures. In: Lindhe J, the width of keratinized tissue in patients
soft tissue regeneration because they Lang NP, Karring T, eds. Clinical Periodon- with fixed prosthetic restorations: A ran-
maintain their 3D structure and sub- tology and Implant Dentistry. 5th ed. domized prospective clinical trial. J Clin
sequently offer good mechanical Oxford, United Kingdom: Blackwell; Periodontol. 2009;36:868–876.
properties. 2008:1089. 21. Vignoletti F, Nunez J, Discepoli N,
8. Rourke K, McKinny S, St Martin B. et al. Clinical and histological healing of
The use of soft tissue substitutes for
Effect of wound closure on buccal muco- a new collagen matrix in combination with
augmentation purposes has increased sal graft harvest site morbidity: Results of the coronally advanced flap for the treat-
over the last few years, but still has not a randomized prospective trial. Urology. ment of Miller class-i recession defects: An
made the commercial breakthrough 2012;79:443–447. experimental study in the minipig. J Clin
comparable to that of bone substitutes. 9. Whitaker IS, Prowse S, Potokar TS. Periodontol. 2011;38:847–855.
Nevertheless, recently, tissue-engi- A critical evaluation of the use of Biobrane 22. Badia A. Arthroscopic indications
neered three-dimensional (3D) oral as a biologic skin substitute: A versatile and technique for artelon interposition ar-
mucosal grafts have been tested and tool for the plastic and reconstructive sur- throplasty of the thumb trapeziometacar-
geon. Ann Plast Surg. 2008;60:333–337. pal joint. Tech Hand Up Extrem Surg.
could offer a promising alternative to 10. Blok CS, Vink L, de Boer EM, et al. 2008;12:236–241.
conventional grafts. Furthermore, new Autologous skin substitute for hard-to-heal 23. Gisselfält K, Edberg B, Flodin P.
synthetic electrospun nanofibrous scaf- ulcers: Retrospective analysis on safety, Synthesis and properties of degradable
folds have been introduced in skin applicability, and efficacy in an outpatient poly(urethane urea)s to be used for

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

ligament reconstructions. Biomacromole- self-inflating injectable tissue expander pel- 50. Singh J, Prasad K, Lalitha RM,
cules. 2002;3:951–958. lets. Plast Reconstr Surg. 2006;118:1447– et al. Buccal pad of fat and its applications
24. Mizutani J, Matsubara T, Fukuoka 1452. in oral and maxillofacial surgery: A review
M, et al. Application of full-scale three- 37. Sharony Z, Rissin Y, Ullmann Y. of published literature (February) 2004 to
dimensional models in patients with rheu- Postburn scalp reconstruction using (July) 2009. Oral Surg Oral Med Oral Path-
matoid cervical spine. Eur Spine J. 2008; a self-filling osmotic tissue expander. ol Oral Radiol Endod. 2010;110:698–705.
17:644–649. J Burn Care Res. 2009;30:744–746. 51. Fan L, Chen G, Zhao S, et al. Clin-
25. Sonntag R, Reinders J, Kretzer JP. 38. Gronovich Y, Tuchman I, ical application and histological observa-
What’s next? alternative materials for artic- Binenboym R, et al. Reconstruction with tion of pedicled buccal fat pad grafting.
ulation in total joint replacement. Acta Bio- an osmotic tissue expander in pediatric Chin Med J (Engl). 2002;115:1556–1559.
mater. 2012;8:2434–2441. patients. Plast Reconstr Surg. 2012;129: 52. Meyer E, Liebenberg SJ, Fagan JJ.
26. Friberg B, Jemt T. Soft tissue aug- 863e–865e. Buccal fat paddA simple, underutilized
mentation in connection to dental implant 39. Vriens AP, Waaijman T, van den flap. S Afr J Surg. 2012;50:47–49.
treatment using a synthetic, porous mate- Hoogenband HM, et al. Comparison of 53. Poeschl PW, Baumann A,
rialdA case series with a 6-month follow- autologous full-thickness gingiva and skin Russmueller G, et al. Closure of oroantral
up. Clin Implant Dent Relat Res. 2012;14: substitutes for wound healing. Cell Trans- communications with Bichat’s buccal fat
872–881. plant. 2008;17:1199–1209. pad. J Oral Maxillofac Surg. 2009;67:
27. Jayabalan M, Rathinam K. Effects 40. Levine RA, Huynh-Ba G, Cochran 1460–1466.
of biostability and morphology on host DL. Soft tissue augmentation procedures 54. Zhong LP, Chen GF, Fan LJ, et al.
response of polyurethane-based soft for mucogingival defects in esthetic sites. Immediate reconstruction of maxilla with
tissue implants. Clin Mater. 1992;11: Int J Oral Maxillofac Implants. 2014;29 bone grafts supported by pedicled buccal
179–191. (suppl):155–185. fat pad graft. Oral Surg Oral Med Oral
28. Kaner D, Friedmann A. Soft tissue 41. Gupta V, Bains VK, Mohan R, et al. Pathol Oral Radiol Endod. 2004;97:
expansion with self-filling osmotic tissue Bridge flap technique as a single-step 147–154.
expanders before vertical ridge augmenta- solution to mucogingival problems: A 55. Hassani A, Khojasteh A, Alikhasi
tion: A proof of principle study. J Clin Pe- case series. Contemp Clin Dent. 2011;2: M, et al. Measurement of volume changes
riodontol. 2011;38:95–101. 110–114. of sinus floor augmentation covered with
29. Dhadse PV, Yeltiwar RK, 42. Wessel JR, Tatakis DN. Patient buccal fat pad: A case series study. Oral
Bhongade ML, et al. Soft tissue expansion outcomes following subepithelial connec- Surg Oral Med Oral Pathol Oral Radiol
before vertical ridge augmentation: Inflat- tive tissue graft and free gingival graft pro- Endod. 2009;107:369–374.
able silicone balloons or self-filling osmotic cedures. J Periodontol. 2008;79:425–430. 56. El Haddad SA, Abd El Razzak MY,
tissue expanders? J Indian Soc Periodon- 43. Wei PC, Laurell L, Geivelis M, et al. El Shall M. Use of pedicled buccal fat
tol. 2014;18:433–440. Acellular dermal matrix allografts to pad in root coverage of severe gingival
30. Mertens C, Thiele O, Engel M, et al. achieve increased attached gingiva. Part recession defect. J Periodontol. 2008;79:
The use of self-inflating soft tissue expand- 1. A clinical study. J Periodontol. 2000; 1271–1279.
ers prior to bone augmentation of atro- 71:1297–1305. 57. Agarwal C, Gayathri GV, Metha
phied alveolar ridges. Clin Implant Dent 44. Uijlenbroek HJ, Liu Y, He JF, et al. DS. An innovative technique for root cov-
Relat Res. 2015;17:44–51. Expanding soft tissue with Osmed tissue erage using pedicled buccal fat pad. Con-
31. Park SH, Choi SK, Jang JH, et al. expanders in the goat maxilla. Clin Oral temp Clin Dent. 2014;5:386–388.
Self-inflating oral tissue expander for ridge Implants Res. 2011;22:121–128. 58. Amin MA, Bailey BM, Swinson B,
augmentation in the severely atrophic 45. Kao SY, Lui MT, Fong J, et al. A et al. Use of the buccal fat pad in the
mandible. J Korean Assoc Oral Maxillofac method using vestibulo-sulcoplasty com- reconstruction and prosthetic rehabilitation
Surg. 2013;39:31–34. bining a split-thickness skin graft and of oncological maxillary defects. Br J Oral
32. Abrahamsson P, Isaksson S, a palatal keratinized mucosa graft for Maxillofac Surg. 2005;43:148–154.
Andersson G. Guided bone generation in peri-implant tissue secondary to oral can- 59. Farré-Guasch E, Martí-Pagè C,
a rabbit mandible model after periosteal cer surgery. J Oral Implantol. 2005;31: Hernádez-Alfaro F, et al. Buccal fat pad,
expansion with an osmotic tissue 186–191. an oral access source of human adipose
expander. Clin Oral Implants Res. 2011; 46. Tideman H. A technique of vestib- stem cells with potential for osteochondral
22:1282–1288. ular plasty using a free mucosal graft from tissue engineering: An in vitro study.
33. Von See C, Rücker M, Bormann the cheek. Int J Oral Surg. 1972;1:76–80. Tissue Eng Part C Methods. 2010;16:
KH, et al. Using a novel self-inflating hydro- 47. Shore JW, Foster CS, Westfall CT, 1083–1094.
gel expander for intraoral gingival tissue et al. Results of buccal mucosal grafting for 60. Chambrone L, Chambrone D,
expansion prior to bone augmentation. Br patients with medically controlled ocular Pustiglioni FE, et al. Can subepithelial con-
J Oral Maxillofac Surg. 2010;48:e5–6. cicatricial pemphigoid. Ophthalmology. nective tissue grafts be considered the
34. Jenq TF, Hilliard SM, Kuang AA. 1992;99:383. gold standard procedure in the treatment
Novel use of osmotic tissue expanders to 48. Abad-Gallegos M, Figueiredo R, of Miller Class I and II recession-type de-
treat difficult anterior palatal fistulas. Cleft Rodríguez-Baeza A, et al. Use of Bichat’s fects? J Dent. 2008;36:659–671.
Palate Craniofac J. 2011;48:217–221. buccal fat pad for the sealing of orosinusal 61. Fu JH, Su CY, Wang HL. Esthetic
35. Wysocki M, Kobus K, Szotek S, communications. A presentation of 8 soft tissue management for teeth and im-
et al. Biomechanical effect of rapid muco- cases. Med Oral Patol Oral Cir Bucal. plants. J Evid Based Dent Pract. 2012;12:
periosteal palatal tissue expansion with the 2011;16:e215–219. 129–142.
use of osmotic expanders. J Biomech. 49. Abuabara A, Cortez AL, Passeri 62. Craft RO, Rebecca AM, Flahive C,
2011;44:1313–1320. LA, et al. Evaluation of different treatments et al. Does size matter? Technical consid-
36. Mischkowski RA, Kübler AC. Cor- for oroantral/oronasal communications: erations of a regenerative tissue matrix for
rection of congenital nasal hypoplasia Experience of 112 cases. Int J Oral Max- use in reconstructive surgery. Can J Plast
associated with Kallmann syndrome using illofac Surg. 2006;35:155–158. Surg. 2011;19:51–52.

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

63. Sheridan R, Choucair R, Donelan 75. Jenabian N, Haghanifar S, 87. Tetteh G, Khan AS, Delaine-Smith
M, et al. Acellular allodermis in burns sur- Maboudi A, et al. Clinical and radiographic RM, et al. Electrospun polyurethane/hy-
gery: 1-Year results of a pilot trial. J Burn evaluation of Bio-Gen with biocollagen droxyapatite bioactive scaffolds for bone
Care Rehabil. 1998;19:528–530. compared with Bio-Gen with connective tissue engineering: The role of solvent
64. Yim H, Cho YS, Seo CH, et al. The tissue in the treatment of class II furcation and hydroxyapatite particles. J Mech Be-
use of AlloDerm on major burn patients: defects: A randomized clinical trial. J Appl hav Biomed Mater. 2014;39:95–110.
AlloDerm prevents post-burn joint contrac- Oral Sci. 2013;21:422–429. 88. Qian T, Wang Y. Micro/nano-fabri-
ture. Burns. 2010;36:322–328. 76. Rastogi S, Modi M, Sathian B. The cation technologies for cell biology. Med
65. Baxter RA. Long-term follow-up efficacy of collagen membrane as a biode- Biol Eng Comput. 2010;48:1023–1032.
with AlloDerm in breast reconstruction. gradable wound dressing material for surgi- 89. Telemeco TA, Ayres C, Bowlin GL,
Plast Reconstr Surg Globe Open. 2013; cal defects of oral mucosa: A prospective et al. Regulation of cellular infiltration into
1:1–2. study. J Oral Maxillofac Surg. 2009;67: tissue engineering scaffolds composed of
66. Butterfield JL. 440 Consecutive 1600–1606. submicron diameter fibrils produced by
immediate, implant-based, single-surgeon 77. Schlee M, Ghanaati S, electrospinning. Acta Biomater. 2005;1:
breast reconstructions in 281 patients: A Willershausen I, et al. Bovine pericardium 377–385.
comparison of early outcomes and costs based non-cross linked collagen matrix for 90. Iafiscol M, Quirici N, Foltran I, et al.
between SurgiMend fetal bovine and Allo- successful root coverage, a clinical study Electrospun collagen mimicking the recon-
Derm human cadaveric acellular dermal in human. Head Face Med. 2012;8:6. stituted extracellular matrix improves oste-
matrices. Plast Reconstr Surg. 2013;131: 78. Guo J, Chen H, Wang Y, et al. A oblastic differentiation onto titanium
940–951. novel porcine acellular dermal matrix scaf- surfaces. J Nanosci Nanotechnol. 2013;
67. Buinewicz B, Rosen B. Acellular fold used in periodontal regeneration. Int J 13:4720–4726.
cadaveric dermis (AlloDerm): A new alter- Oral Sci. 2013;5:37–43. 91. Jin G, Prabhakaran MP,
native for abdominal hernia repair. Ann 79. Wang LH, Greenwell H, Fiorellini Ramakrishna S. Stem cell differentiation
Plast Surg. 2004;52:188–194. J, et al. Periodontal regeneration. to epidermal lineages on electrospun
68. Xu HM, Wang ZJ, Han JG, et al. J Periodontol. 2005;76:1601–1622. nanofibrous substrates for skin tissue
Application of acellular dermal matrix for 80. Ge S, Zhao N, Wang L, et al. Ef- engineering. Acta Biomater. 2011;7:
intestinal elongation in animal models. World fects of hydroxyapatite nanostructure on 3113–3122.
J Gastroenterol. 2010;16:2023–2027. channel surface of porcine acellular dermal 92. Falanga V, Margolis D, Alvarez O,
69. Ruiz-Magaz V, Hernández-Alfaro matrix scaffold on cell viability and osteo- et al. Rapid healing of venous ulcers and
F, Díaz-Carandell A, et al. Acellular dermal genic differentiation of human periodontal lack of clinical rejection with an allogeneic
matrix in soft tissue reconstruction prior to ligament stem cells. Int J Nanomedicine. cultured human skin equivalent. Human
bone grafting. A case report. Med Oral 2013;8:1887–1895. Skin Equivalent Investigators Group. Arch
Patol Oral Cir Bucal. 2010;15:e61–64. 81. Ko Y, Kim N, Park S, et al. Use of Dermatol. 1998;134:293–300.
70. Shulman J. Clinical evaluation of an Artelon(Ò) Cosmetic in soft tissue aug- 93. Felder JM, Goyal SS, Attinger CE.
acellular dermal allograft for increasing the mentation in dentistry. Clin Cosmet Inves- A systematic review of skin substitutes for
zone of attached gingiva. Pract Periodon- tig Dent. 2011;3:33–37. foot ulcers. Plast Reconstr Surg. 2012;
tics Aesthet Dent. 1996;8:201–208. 82. Hefton JM, Madden MR, 130:145–164.
71. Shi LJ, Wang Y, Yang C, et al. Finkelstein JL, et al. Grafting of burn pa- 94. Veves A, Falanga V, Armstrong
Application of acellular dermal matrix in tients with allografts of cultured epidermal DG, et al. Graftskin, a human skin equiva-
reconstruction of oral mucosal defects in cells. Lancet. 1983;2:428–430. lent, is effective in the management of non-
36 cases. J Oral Maxillofac Surg. 2012;70: 83. Lauer G, Otten JE, von Specht BU, infected neuropathic diabetic foot ulcers: A
e586–591. et al. Cultured gingival epithelium. A possible prospective randomized multicenter clini-
72. Almazrooa SA, Noonan V, Woo SB. suitable material for pre-prosthetic surgery. cal trial. Diabetes Care. 2001;24:290–295.
Resorbable collagen membranes: Histo- J Craniomaxillofac Surg. 1991;19:21–26. 95. Zeng Q, Macri LK, Prasad A, et al.
pathologic features. Oral Surg Oral Med Or- 84. Mohammadi M, Shokrgozar MA, Skin tissue engineering. Comprehen Bio-
al Pathol Oral Radiol. 2014;118:236–240. Mofid R. Culture of human gingival fibro- mat. 2011;5:467–499.
73. Glaum R, Wiedmann-Al-Ahmad M, blasts on a biodegradable scaffold and 96. Moharamzadeh K, Colley H,
Huebner U, et al. Tissue engineering of evaluation of its effect on attached gingiva: Murdoch C, et al. Tissue-engineered oral
composite grafts: Cocultivation of human A randomized, controlled pilot study. mucosa. J Dent Res. 2012;91:642–650.
oral keratinocytes and human osteoblast- J Periodontol. 2007;78:1897–1903. 97. Izumi K, Neiva RF, Feinberg SE.
like cells on laminin-coated polycarbonate 85. Mohammadi M, Mofid R, Intraoral grafting of tissue-engineered
membranes and equine collagen mem- Shokrgozar MA. Peri-implant soft tissue human oral mucosa. Int J Oral Maxillofac
branes under different culture conditions. management through use of cultured gin- Implants. 2013;28:e295–303.
J Biomed Mater Res A. 2010;93:704–715. gival graft: A case report. Acta Med Iran. 98. Kim RY, Fasi AC, Feinberg SE. Soft
74. Nocini PF, Castellani R, Zanotti G, 2011;49:319–324. tissue engineering in craniomaxillofacial
et al. Extensive keratinized tissue augmen- 86. Marston WA, Hanft J, Norwood P, surgery. Ann Maxillofac Surg. 2014;4:4–8.
tation during implant rehabilitation after Le et al. The efficacy and safety of Dermagraft in 99. Kuo S, Zhou Y, Kim HM, et al. Bio-
Fort I osteotomy: Using a new porcine col- improving the healing of chronic diabetic foot chemical Indicators of Implantation Suc-
lagen membrane (Mucoderm). J Craniofac ulcers: Results of a prospective randomized cess of tissue-engineered oral mucosa.
Surg. 2013;2:799–803. trial. Diabetes Care. 2013;26:1701–1705. J Dent Res. 2015;94:78–84.

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
View publication stats