THE ANATOMICAL RECORD 297:1625 (2014)

Tissue Engineering in Periodontal

Tissue
TAKANORI IWATA,1,2 MASAYUKI YAMATO,1 ISAO ISHIKAWA,1
TOMOHIRO ANDO,2 AND TERUO OKANO1*
1
Institute of Advanced Biomedical Engineering and Science, Tokyo Womens Medical
University, Shinjuku-ku, Tokyo, Japan
2
Department of Oral and Maxillofacial Surgery, Tokyo Womens Medical University,
Shinjuku-ku, Tokyo, Japan

ABSTRACT
Periodontitis, a recognized disease worldwide, is bacterial infectioninduced inflammation of the periodontal tissues that results in loss of alveolar bone. Once it occurs, damaged tissue cannot be restored to its original
form, even if decontaminating treatments are performed. For more than
half a century, studies have been conducted to investigate true periodontal
regeneration. Periodontal regeneration is the complete reconstruction of
the damaged attachment apparatus, which contains both hard tissue (alveolar bone and cementum) and soft tissue (periodontal ligament). Several
treatments, including bone grafts, guided tissue regeneration with physical
barriers for epithelial cells, and growth factors have been approved for clinical use; however, their indications and outcomes are limited. To overcome
these limitations, the concept of tissue engineering was introduced. Combination treatment using cells, growth factors, and scaffolds, has been
studied in experimental animal models, and some studies have been translated into clinical trials. In this review, we focus on recent progressive tissue engineering studies and discuss future perspectives on periodontal
C 2013 Wiley Periodicals, Inc.
regeneration. Anat Rec, 297:1625, 2014. V

Key words: periodontal tissue; periodontal regeneration; periodontal ligament; bone; cementum; stem cells;
cytotherapy; clinical trials

Periodontitis is a global disease that destroys the

tooth-supporting attachment apparatus, which consists
of alveolar bone, cementum, and periodontal ligament.
Recent studies have reported numerous associations
between periodontitis and systemic diseases, such as
cardiovascular disease (de Oliveira et al., 2010) and
diabetes mellitus (Lalla and Papapanou, 2011), as well
as a higher risk of preterm low birth-weight babies
(Offenbacher et al., 1996). Furthermore, research has
recently shown that Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) is associated with severe
periodontitis (Vescovi et al., 2011). Consequently, periodontal treatment may not only contribute to oral
hygiene but also improve systemic conditions (Seymour
et al., 2007).
Conventional treatments such as scaling, root-planing,
and surgical cleaning are currently performed to remove
the bacteria and contaminated tissue. However, these
C 2013 WILEY PERIODICALS, INC.
V

procedures frequently result in the formation of weak

attachment called a long junctional epithelium, LJE,
(Caton et al., 1980). In addition, these conventional

Grant sponsor: The Ministry of Education, Culture, Sports,

Science and Technology (MEXT), Japan. Grant sponsor: Creation of innovation centers for advanced interdisciplinary
research areas Program in the Project for Developing Innovation Systems Cell Sheet Tissue Engineering Center (CSTEC).
*Correspondence to: Teruo Okano, Ph.D., Institute of Advanced
Biomedical Engineering and Science, Tokyo Womens Medical
University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666,
Japan. Fax: 181333596046. E-mail: okano.teruo@twmu.ac.jp
Received 13 September 2013; Accepted 13 September 2013.
DOI 10.1002/ar.22812
Published online 2 December 2013 in Wiley Online Library
(wileyonlinelibrary.com).

TISSUE ENGINEERING IN THE PERIODONTAL TISSUE

17

Fig. 2. Higher magnification of the palatal side of Fig. 1 (natural periodontal tissue). Sections were stained with Azan (left) or hematoxylin
eosin (right). D: dentin, C: cementum, PDL: periodontal ligament, B:
alveolar bone (bars, 50 mm).

Fig. 1. Photomicrograph of canine maxillary premolar. Periodontal

defect was mechanically created in the left (buccal) side of the teeth
(5 mm in height). Six week after the cell transplantation, the sample
was decalcified in Plank-Rychro solution for 6 weeks, routinely processed into 6-mm thick paraffin-embedded sections, and stained with
Azan. This picture shows both natural periodontal tissue in the right
(palatal) side and spontaneously regenerated tissue in the left (buccal)
side simultaneously. G: gingiva, D: dentin, B: alveolar bone, P: dental
pulp, NB: newly-formed bone (bar, 1 mm).

procedures cannot restore the periodontal tissue to its

original form, and the decrease in bone height and gingival recession usually cause aesthetic and functional
problems. Several regenerative procedures have already
been introduced to clinical practice to overcome these
problems, including bone grafts, guided tissue regeneration, and enamel matrix derivative. However, the outcomes of these procedures have limited success and have
poor clinical predictability (Esposito et al., 2009). Therefore, research has turned to investigating stem cellbased approaches for periodontal regeneration [see in
review (Ishikawa et al., 2009)].
Tissue engineering, a concept proposed by Langer
and Vacanti, is widely accepted in the field of regenerative medicine to create replacement tissues using a combination of cells, scaffolds, and growth factors (Langer

Fig. 3. Higher magnification of the buccal side of Fig. 1 (spontaneous healing model). The most coronal area of newly formed periodontal tissue. Note newly formed cementum covering the rough surface of
dentin. Arrowhead shows the coronal extention of new cementum. In
this case, well-oriented fibers between cementum to alveolar bone
was not observed (bar, 50 mm).

and Vacanti, 1993). However, there are limitations to

this concept; grafts may be rejected as a result of inflammation caused by scaffold degradation, necrosis, or
unstable transplanted cells (Yang et al., 2005). Several
technologies using new biomaterials are being introduced to overcome these limitations (Williams, 2009). In
this review, we focus on recent studies involving tissue
engineering and regenerative medicine using biomaterials in the periodontal field.

PERIODONTAL TISSUE
Periodontal tissue consists of four component structures: alveolar bone, periodontal ligament, cementum,

18

IWATA ET AL.

cially in anterior teeth (Fig. 4c). If periodontitis is left

untreated, the attachment apparatus is completely
destroyed resulting in tooth mobility and loss.
The purpose of conventional periodontal therapies,
such as scaling, root planing, and periodontal surgery, is
to remove the bacterial pathogens and infected granulation tissues surrounding the teeth. These procedures can
halt the disease process, but they cannot restore the tissue to its original form. Additionally, the treatments
may result in the formation of an LJE; thus, patients
tend to relapse without maintenance therapies (Axelsson
and Lindhe, 1981). The final goal of periodontal regeneration is to reform the lost tissue and restore to its original form (bone structures with well-oriented periodontal
ligament anchoring to dental cementum).

CONVENTIONAL APPROACHES FOR

PERIODONTAL REGENERATION BONE
GRAFT MATERIALS

Fig. 4. (a) Inflammation is observed in anterior teeth. Arrowheads

indicate gingival rubor and swelling. (b) Severe periodontitis. Fiftyyear-old male, who did not go to dental office for 30 years, complained tooth mobility. Radiographic examination (right panel) indicated bone resorption beyond the apex of the first molar (arrowhead).
(c) Aesthetic problems after periodontal treatment. Although deep
pockets were eliminated by conventional therapies, aesthetic, and
functional problems are still remaining due to gingival recession and
flaring out.

and gingiva (Figs. 13). Specifically, alveolar bone, periodontal ligament, and cementum are called the
attachment apparatus and are the target tissues for
periodontal regeneration (Fig. 2).

Pathogenesis and Treatment of Periodontal

Disease
Gingivitis or gingival inflammation is initiated and
promoted by the accumulation of dental plaque (Fig. 4a).
If the inflammation is localized within the gingiva,
proper plaque control can restore a healthy condition.
However, once the inflammation and the host immune
response expand to the adjacent periodontal tissues
(alveolar bone, cementum, and periodontal ligament),
connective tissues, and bone become permanently damaged. This spread of inflammation is called
periodontitis, and spontaneous healing is not expected
(Fig. 4b). Although decontaminating procedures can be
performed, the height of bone will not improve. Moreover, gingival recessions create aesthetic issues, espe-

Bone graft regeneration is still somewhat controversial; bone grafts may not always regenerate true periodontal tissue with well-oriented fibers anchoring the
cementum to the alveolar bone (Mellonig, 1992). Histological analyses have revealed that LJE between the
alveolar bone and root surface often migrate apically. In
addition, root resorption and ankylosis are occasionally
observed (Table 1).
Clinical studies have shown that the gain of bone
height is 3.0 mm irrespective of the type of bone graft
material (Mellonig, 1992). The gold standard for bone
grafting is autologous bone, which is capable of osteogenesis, osteoinduction, and osteoconduction. For these
grafts, a portion of bone is taken from a healthy site of
the patient receiving the graft. The advantage of autologous bone is that it inherently has the vital structures of
bone tissue and contains cells, minerals, and proteins.
The disadvantages of autologous bone grafts are the
patient morbidities at the removal sites and limited
amount of bone that can be harvested.
As a result of these disadvantages, many allogeneic
bone grafts and xenograft materials have been investigated and approved and are commercially available
(Miron and Zhang, 2012). However, clinicians must
consider the potential risks of disease transmission,
rejection, and resorption when using these grafts. There
are two types of allografts: demineralized freeze-dried
bone allografts and freeze-dried bone allografts. Both of
these types of allografts are chemically pretreated,
retaining osteoinductive proteins such as BMPs and
TGF-bs, to enhance the osteoinduction of endogenous
mesenchymal stromal cells. It is thought that the
process of demineralization enhances the release of
inherent growth factors, such as BMPs (Urist, 1965).
Xenografts are derived from non-human species, such
as bovine, porcine, or equine animals. They are usually
sintered and chemically pretreated to remove their antigenicity. The advantage of these products is that the
shape of the gragt can be retained, because the resorption of these materials is relatively slow. Although they
are only capable of osteoconductivity, the safety and
efficacy of these products have been proved clinically
(Camelo et al., 1998; Richardson et al., 1999).
Because of the risks associated with allograft and
xenograft materials, researchers have also investigated

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TISSUE ENGINEERING IN THE PERIODONTAL TISSUE

TABLE 1. Bone graft materials

Autologous bone

Allogeneic bone

Demineralized
freeze-dried
bone allograft (DFDBA)
Freeze-dried bone
allograft (DFDBA)

Xenogeneic bone
Artificial
materials

Sintered
hydroxyapatite (HA)
b-tricalcium phosphate (TCP)
Natural products
(coral, citosan etc.)

Benefit

Risk

Osteogenic, osteoinductive
and osteoconductive no
immunological rejection
living cells and matrices
Osteoinudctive and
osteoconductive

Morbidity at donor sites

amount of bone volume is limited
rapid absorption

Osteoinudctive and
osteoconductive
Osteoconductive
Osteoconductive
Osteoconductive
Osteoconductive,
low immunological
rejection

Potential of infection and

immunological rejection
Potential of infection and
immunological rejection
Potential of infection and
immunological rejection
Slow resorption or non-resorbable
Slow resorption or non-resorbable
Rapid resorption
Slow resorption or non-resorbable

Tissue engineering in periodical tissue

synthesized graft materials, including polymer and inorganic composite grafts, to regenerate bone [see in review
(Rezwan et al., 2006)]. Specifically hydroxyapatite (HA)
and b-tricalcium phosphate (b-TCP) have been studied
in human periodontal defect models. Although synthesized materials are only osteoconductive (not osteogenic
or osteoinductive), they can successfully restore bone
defects if the environment is favorable. Recently, moldable in situ hardening polylactide-coated TCP has been
developed and applied to repair bone defects in rabbits;
the results showed good biocompatibility (Schmidlin
et al., 2013).
Natural products, such as coral, have also been investigated for bone grafting because their structures are
similar to those of bone (Damien and Revell, 2004). Like
synthetic materials, natural products are only osteoconductive, but they are cost-effective and considered to
pose no risk to human health.

Physical Barriers for Epithelial Tissue

In the past, it was predicted that the periodontal
ligament tissue contains the cells responsible for periodontal regeneration (Melcher, 1976); recently, such
multipotent cells have been identified in periodontal
tissue (Seo et al., 2004; Gay et al., 2007; Iwata et al.,
2010). In the 1980s, physical barriers were introduced
into periodontal surgeries to eliminate epithelial downgrowth, and selective proliferation of mesenchyme
derived cells was enhanced (Nyman et al., 1982). Physical barriers have been widely employed in clinical practices, but this procedure involves technically difficult
steps and potential complications, such as exposure of
the barrier or infection. Various barrier membranes
have been developed and are commercially available.

Enamel Matrix Derivatives (EMD)

R ), a
EMD (commercially available as EMDOGAINV
mixture of porcine immature enamel extracts, has been
showed to effectively treat infrabony periodontal

defects (Heijl et al., 1997). A meta-analysis (eight trials) showed that EMD-treated sites displayed statistically significant improvements compared with sites
treated with flap surgery (Esposito et al., 2009). The
main component of EMD is amelogenin, a majority of
enamel proteins, and amelogenin is believed to possess
the properties needed to regenerate periodontal tissue
because the expression of amelogenin was observed in
developing dental root (Hammarstrom, 1997). In addition to enamel matrix proteins, several studies have
demonstrated that EMD contains small amount of
growth factors, such as BMPs (Iwata et al., 2002; Johnson et al., 2009) and TGF-b1 (Suzuki et al., 2005),
explaining the complex effects of EMD. A particularly
interesting study found that propylene glycol alginate
(PGA), the vehicle of EMD, has antibacterial properties, suggesting that the combination of EMD and PGA
enhances not only periodontal (Sculean et al., 2001)
but also epithelial wound healing (Mirastschijski et al.,
2004; Al-Hezaimi et al., 2012).

Tissue Engineering Approaches for Periodontal

Regeneration Growth Factors used for
Periodontal Regeneration
Combining growth factors and carriers (scaffolds) for
periodontal regeneration has also been investigated.
This concept of using a drug delivery system (DDS) was
introduced to prolong the therapeutic effects of growth
factors (Chen et al., 2009). In this section, the application of growth factors to periodontal defect models in
large animals is reviewed.

Platelet-Derived Growth Factor (PDGF)-BB and

Insulin-Like Growth Factor One (IGF-1)
The combination of PDGF-BB and IGF-1 was the first
reported use of growth factors for periodontal regeneration,
and it was tested in a canine model (Lynch et al., 1989). A
subsequent clinical trial also showed that this combination
of growth factors in a methylcellulose vehicle was safe and

20

IWATA ET AL.

that it enhanced periodontal regeneration (Howell et al.,

1997). Giannobile et al. demonstrated that PDGF-BB alone
significantly stimulates periodontal regeneration, but that
IGF-1 alone does not alter periodontal wound healing in a
nonhuman primate model (Giannobile et al., 1996). A multicenter randomized controlled trial with 180 subjects
enrolled in 11 clinical centers showed the safety and efficacy of PDGF-BB soaked in b-TCP matrix for the treatment of advanced periodontal osseous defects (Nevins
et al., 2005, 2013). This product is commercially available
R (Osteohealth, Shirley, NY).
as GEM 21 SV
Several types of carriers for sustained-releasing of
PDGF-BB, including porous poly(L-lactide) membranes
(Park et al., 1998), chitosan sponges (Park et al., 2000),
chitosan/TCP sponges (Lee et al., 2000), and nanofibrous
scaffolds (Wei et al., 2006), have been investigated, and
their efficacies were confirmed.

Bone Morphogenetic Proteins (BMPs) and

Transforming Growth Factor-bs (TGF-bs)
The BMP/TGF-b signaling pathway mediates osteoblastic differentiation and in vivo bone formation; BMP2
in particular has been thoroughly studied for periodontal
regeneration. Several carriers, including autologous
blood and poly(D,L-lactide-co-glycolide) (PLGA) particles
(Sigurdsson et al., 1995), PLGA and gelatin sponges
(Kinoshita et al., 1997), and absorbable collagen sponges
(ACS; Selvig et al., 2002), have been investigated. The
combination of BMP2/ACS is commercially available as
R bone graft (Medtronic, Minneapolis, MN); it is
INFUSEV
approved for bone augmentation for sinus lifting and
implant dentistry, but not for periodontal osseous defects
at this time. Other members of the BMP family, such as
BMP-7/OP-1 (Giannobile et al., 1998; Ripamonti et al.,
2001), BMP-12/GDF-7 (Wikesjo et al., 2004), BMP-14/
GDF-5 (Kwon et al., 2010; Lee et al., 2010), have also
been investigated in large animal models, and their efficacies for periodontal regeneration were observed in all
studies. A recent study compared the carriers, b-TCP
and ACS, for BMP14/GDF5 delivery in a canine periodontal defect model (Kim et al., 2013). The authors
observed that b-TCP was superior for new bone
formation.
Whether TGF-b1 directly enhances periodontal regeneration is still controversial (Tatakis et al., 2000); however, it has been reported that TGF-b1 induced
endochondral bone formation (Serra et al., 1999).
R
Another study suggested that TGF-b3 in MatrigelV
matrix (BD Biosciences, San Jose, CA) in combination
with minced muscle tissue significantly enhanced the
periodontal regeneration in class III furcation defects in
P. ursinus (Ripamonti et al., 2009).

Basic Fibroblast Growth Factor (bFGF, known

as FGF2)
The use of bFGF, a growth factor that is already utilized clinically for wound healing in patients with
intractable skin ulcers, has been investigated for bone
formation and periodontal regeneration. Its efficacy on
periodontal regeneration was demonstrated in beagles
and nonhuman primates (Murakami et al., 1999, 2003;
Takayama et al., 2001). A multicenter, randomized
clinical trial was performed using a 3% hydroxypropyl

cellulose carrier (Kitamura et al., 2008, 2011); the

results showed that bFGF was safe and effective for
periodontal regeneration. Several bFGF carriers,
including sandwich membranes of collagen sponge
with bFGF-incorporated gelatin microsphere (Nakahara et al., 2003), collagen gel (Sato et al., 2004), and
b-TCP (Oi et al., 2009; Anzai et al., 2010), have been
investigated.

Brain-Derived Neurotrophic Factor (BDNF)

Despite its name, BDNF is found in several tissues,
even in PDL cells (Kurihara et al., 2003). The application of BDNF in combination with atelocollagen sponge
stimulated the formation of new alveolar bone, cementum, and connective fibers; the fibers were inserted into
the newly formed cementum and bone in a canine class
III furcation defect model. BDNF also stimulated blood
capillary formation (Takeda et al., 2005). A recent study
claimed that scaffolds made from high-molecular-weight
hyaluronic acid improved the regenerative capacity of
BDNF in a canine periodontal defect model (Takeda
et al., 2011).

Cytotherapy for Periodontal Regeneration

Several types of mesenchyme-derived cells have been
investigated for periodontal regeneration.

Periodontal Ligament-Derived Stem Cells

(PDLSCs) or Multipotent Mesenchymal Stromal
Cells (PDL-MSCs)
Shi and colleagues isolated and investigated a population of multipotent cells from human PDL tissues, called
PDLSCs, which possessed the ability to form all components of the attachment apparatus when they were subcutaneously transplanted with b-TCP/HA scaffolds in
immunodeficient mice (Seo et al., 2004). When autologous PDLSCs seeded in a HA/TCP scaffold were transplanted into periodontal defects of miniature pigs,
complete periodontal regeneration was observed (Liu
et al., 2008). Further studies used temperature responsive culture dishes to create PDL-MSC sheets. Threelayered canine PDL-MSC sheets were fabricated using
R , PGA Feltwoven polyglycolic acid (PGA) (NeoveilV
Sheet Type, 0.15 mm in thickness: Gunze, Tokyo, Japan)
and transplanted into the denuded root surface autologously, while bone defects were filled with porous b-TCP
(Iwata et al., 2009; Tsumanuma et al., 2011). After healing, complete periodontal regeneration was observed in
both studies. In addition, PDLSC sheets without
bone graft materials can regenerate complete periodontal tissue in a canine furcation defect model (Figs. 5
and 6). A recent study suggested that the allogeneic
transplantation of PDLSC sheets with HA/TCP was
applicable to periodontal regeneration; its safety and
efficacy were confirmed in a swine model (Ding et al.,
2010).

Bone Marrow-derived MSCs (BM-MSCs)

Bone marrow-derived MSCs are thought to be trophic
and immunomodulatory, as well as multipotent (Caplan
and Correa, 2011). In fact, MSCs have been utilized in

TISSUE ENGINEERING IN THE PERIODONTAL TISSUE

21

Fig. 5. Class II furcation defects were created surgically at mandibular first molar (a), and the osseous defects were filled with rubber
base impression materials to induce inflammation (b). At the same
time, premolars were extracted to make PDLSC sheets. Eight weeks
after the first surgery (c), the transplantation of PDLSC sheets was

performed. Class II furcation defect (5 3 5 3 5 mm3) was recreated

(e) after the removal of the impression material and inflamed tissues
(d). Six PDLSC sheets (arrowheads) were transplanted without any
other graft materials autologously (f).

numerous clinical trials for various diseases, including

graft versus host disease, acute myocardial infarction,
stroke, acute kidney failure, and tendonitis.
Clinical trials using BM-MSCs with platelet-rich
plasma (PRP) have also been conducted, and the results
demonstrated that periodontal regeneration was successful (Yamada et al., 2006, 2013). Another group used BMMSCs combined with atelocollagen sponges; eleven
patients received the transplantation in Japan, based on

results from previous canine studies (Kawaguchi et al.,

2004; Hasegawa et al., 2006).

Periosteum-Derived Cell Sheets

Cultured periosteum is considered a suitable source of
cells for periodontal regeneration because it is capable of
differentiating into the osteoblast lineage. In one study,
periosteum cell sheet samples (5 3 5 mm) were

22

IWATA ET AL.

harvested from patients by scraping, and an explant culture was performed in each case. Coagulated PRP and
porous HA granules were placed into the infrabony
defects, and 6-week-cultured periosteum sheets were
autologously transplanted in 15 patients (Yamamiya
et al., 2008; Okuda et al., 2009). The results showed that
the cultured periosteum sheets transplantation exhibited
a statistically significant improvement in clinical attachment gain, vertical relative attachment gain, and radiographic infrabony defect fill as compared with the
control.

Adipose-Derived Stem Cells (ADSCs)

ADSCs are a useful source for cell transplantation therapy because they are abundant and easy to obtain. ADSCs
mixed with PRP enhanced the periodontal regeneration
in rats (Tobita et al., 2008). Another source reported that
ADSCs in a fibrin gel scaffold enhanced periodontal
regeneration at applied sites (Murakami, 2011).

Gingival Epithelial Cells and Fibroblasts

Gingival epithelial sheets derived from autologous gingival tissues were developed and applied clinically as a
treatment for chronic desquamative gingivitis (Okuda
et al., 2004). The results showed that human cultured
gingival epithelial sheets promoted gingival augmentation. Recently, an allogeneic cellular product named
GINTUITTM (Organogenesis) was approved by the FDA
and was expected to be commercially available in the
summer of 2012 (http://organogenesis.com/products/
oral_regeneration/oral_regeneration.html). This product
consists of allogeneic cultured keratinocytes and fibroblasts in bovine collagen. In a pivotal, multicenter,
randomized, within-patient, controlled, open-label trial,
McGuire et al. concluded that the product was a safe
and effective therapy for augmenting the keratinized
gingival zone (McGuire et al., 2011).

DISCUSSION AND COMMENTARY

Fig. 6. Eight weeks after the transplantation, radiographic, and hisological analysis of the recipient site was performed. Bone-like structures were observed in CT analysis (a and b). Histological analysis
revealed that the periodontal tissue was regenerated at the 2 mm lingual side from the buccal bone (c) (bar, 1 mm, Azan). Arrows indicate
the bottoms of the defect.

In this review, recent tissue engineering approaches

for treating periodontal regeneration were described.
Because cells or growth factors alone are not sufficient
for periodontal regeneration, great efforts have been
made to optimize the biological and biophysical design of
carriers or scaffolds. Initially, biodegradable polymers
were investigated, but they were not successful because
controlling the shape of implants is difficult owing to
resorption, and inflammation occasionally occurred.
Therefore, more recent clinical studies have often use
collagen or b-TCP as a carrier/scaffold to retain the
cells/growth factors because of the safety, costeffectiveness, osteoconductivity, and biocompatibility of
these materials. Other studies also suggest that welldesigned polymers or synthetic materials can be applicable as carriers/scaffolds for periodontal treatment. For
example, a biphasic scaffold composed of a fused deposition modeling scaffold (bone compartment) and an electrospun membrane (periodontal compartment) with PDL
cell sheets regenerated true periodontal tissue in an
athymic rat subcutaneous model (Vaquette et al., 2012).
In terms of cells, mesenchyme- or neural crest-derived
cells are the most common cell source for periodontal

TISSUE ENGINEERING IN THE PERIODONTAL TISSUE

regeneration, because periodontal tissue originates from

dental cranial neural crest cells (Ishikawa et al., 2009).
One recent study suggested that the transplantation of
induced pluripotent stem (iPS) cells with combination
use of silk scaffold and EMD enhanced periodontal
regeneration in mice (Duan et al., 2011). Furthermore,
allogeneic embryonic stem (ES) cells in a collagen membrane improved periodontal furcation defects in a porcine model (Yang et al., 2013). Although the safety and
efficacy of ES/iPS cells have not yet been proved, they
may become an alternative cell source for periodontal
regeneration in the future (Egusa et al., 2012).

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