The International Journal of Periodontics & Restorative Dentistry437

A Novel Combined Surgical Approach to Vertical
Alveolar Ridge Augmentation with Titanium Mesh,
Resorbable Membrane, and rhPDGF-BB:
A Retrospective Consecutive Case Series

Akiyoshi Funato, DDS1/Tomohiro Ishikawa, DDS2/Hajime Kitajima, DDS3/
Masahiro Yamada, DDS, PhD4/Hidetada Moroi, DMD5
The purpose of this case series was to report the clinical outcomes and histologic
findings of vertical ridge augmentation using a combination of titanium
mesh, resorbable collagen membrane, and recombinant human plateletderived growth factor BB (rhPDGF-BB). Nineteen patients were included, andautogenous bone and anorganic bovine bone particles were used. The bone
graft was mixed with rhPDGF-BB and loaded onto the bony defect up to thelevel of the adjacent alveolar crest. A pre-adapted titanium mesh was placed
over the grafted region and covered with a resorbable collagen membrane,
leaving no areas of the grafted region exposed. Seventeen patients exhibited
good soft tissue healing. Postoperative flap dehiscence occurred relatively earlyin the healing period in one patient, whereas the covering collagen membrane
was exposed during the later phase of the healing period in another. During
reentry surgery for removal of the titanium mesh, three patients with favorable
soft and hard tissue healing underwent bone biopsies for histologic evaluationof the augmented tissue just below the titanium mesh. The mean vertical heightof augmented bone was 8.6 ± 4.0 mm. This report demonstrates the remarkableefficacy of guided bone regeneration using a combination of titanium mesh,resorbable collagen membrane, and rhPDGF for vertical ridge augmentation,
thus expanding the indications for implant therapy and allowing recovery of thethree-dimensional esthetic architecture in a severely absorbed alveolar ridge.
(Int J Periodontics Restorative Dent 2013;33:437–445. doi: 10.11607/prd.1460)
Private Practice, Kanazawa, Ishikawa, Japan.
Private Practice, Hamamatsu, Shizuoka, Japan.
3Private Practice, Iwata, Shizuoka, Japan.
4Senior Assistant Professor, Department of Removable Prosthodontics and Gerodontology,
Tokyo Dental College, Chiba, Japan.
5Assistant Clinical Professor, Department of Periodontology, Tufts University School of
Dental Medicine, Boston, Massachusetts, USA.
1
2

Correspondence to: Dr Masahiro Yamada, Department of Removable Prosthodontics
and Gerodontology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba, 261-8502,
Japan; fax: (+81) 043-270-3935; email: masayamada@tdc.ac.jp.
The first, second, and third authors contributed equally to the present study.
©2013 by Quintessence Publishing Co Inc.

In the field of implant dentistry,vertical ridge augmentation is aclinical challenge with respect toexpanded indications for implant
therapy and the final esthetic results. Many clinical reports havedemonstrated predictable and controllable bone augmentation using
a titanium mesh in combination
with extra- or intraoral autogenous
bone combined with a xenograft invertical bony defects.1–3 However,a titanium mesh has some inherent drawbacks when used in a local ridge augmentation procedure.
It is technically difficult to completely cover bone graft materials
positioned on the complex formof a resorbed alveolar arch with atitanium mesh, which sometimes
results in compromised outcomes.
Alveolar augmentation with a titanium mesh often results in wounddehiscence and mesh exposure,thus increasing the risk of infectionin the grafted region.3–8 Holes inthe titanium mesh also allow leakage of liquid factors, such as exogenous growth factors added to thegrafted region.
Recently, the inherent problems associated with the use of atitanium mesh were overcome by

Volume 33, Number 4, 2013

438
Fig 1 Pre-adaptation of titanium mesh to a recipient site using asterilized study cast prior to surgery.

pre-adapting the mesh before surgery and combining its use with across-linked collagen membranethat has excellent biocompatibility, resistance to infection,9 and aprolonged bioabsorption period(over 24 weeks).10,11 A combinationof titanium mesh and a cross-linked
collagen membrane theoreticallyleads to complementary and synergistic effects and yields manytechnical and biologic improvements compared with conventional
methods.12,13 Fibrous in-growthfrom the gingival flaps occurs in
the covering collagen membraneand prevents wound dehiscence.14
In addition, the membrane is expected to prevent invasion ofsoft tissue into the grafted region
and leakage of bone graft materials and exogenous growth factors, such as recombinant humanplatelet-derived growth factor BB(rhPDGF-BB), through any gaps between titanium mesh units, whichplays an important role in wound
repair processes such as cell proliferation, chemotaxis, and matrix
synthesis.15,16 The purpose of thisretrospective case series was touse visual measurements and his-

tologic evaluations of the regenerative bone to demonstrate theeffectiveness of staged GBR using
a titanium mesh, a cross-linked collagen membrane, and rhPDGF-BB
for vertical ridge augmentation.

general health with no contraindications for surgical treatment. The
treatment plan and sequence were
described in detail to all patients,
who also signed a consent form.

Surgery

Method and materials
Patient selection

A total of nineteen edentulous
ridges (10 maxillary anterior, 4maxillary posterior, 2 mandibular
anterior, and 3 mandibular posterior) of 19 patients (10 women and9 men) with a mean age of 50.2 ±14.4 years (range, 17 to 68 years)
were augmented by staged GBR atthree private clinics between April
2007 and October 2009. All patients requested dental implants to
replace their missing teeth. Upon
comprehensive examination andtreatment planning, a staged approach for vertical alveolar ridge
augmentation and subsequent
implant placement was recommended because of the severityof defects in the proposed implantsites. All patients were in good

The International Journal of Periodontics & Restorative Dentistry

The thickness of the titanium mesh
was 0.1 mm (Jeil Medical). The titanium mesh was preshaped using asterilized study cast before surgery(Fig 1). After local anesthesia, acrestal incision, buccal and lingual
mucoperiosteal flap elevation, andremoval of residual soft tissue on
the bone surface, the cortical bone
was perforated up to the intramarrow space to allow vascular andcellular access into the augmentation site. A periosteal releasing
incision was placed to achieve primary closure of the augmentationsite with tension-free coronal flap
advancement.
In all cases, autogenous bone
was harvested from the mandibular
ramus with a bone scraper (Safescraper Twist, META) and mixed
with blood aspirated from thepatient’s surgical site. Anorganic

439

a

b

c

d

Fig 2a (left) View of severe bone resorption in the right posterior
region of the mandible.
Fig 2b (right) Vertical measurement of the depth of the bone defect from the deepest point of the defect to the most coronal holeof the titanium mesh using a periodontal probe.
Fig 2c A mixture of anorganic bovine bone and autogenous bone
particles harvested from the mandibular ramus and mixed with
rhPDGF-BB.
Fig 2d Complete coverage of the bone-grafted region with an
enzymatically cross-linked collagen membrane.
Fig 2e Augmented bone beneath the titanium mesh after 6
months of healing; note that the entire top surface of the augmented bone has reached a level equivalent to the top of the adjacentbone crest.

bovine bone (0.25- to 1-mm particles; Bio-Oss, Osteohealth) was
mixed with the autogenous bone ina ratio of 1:1 or 4:1. The bone grafte

mixture was soaked in rhPDGF(Gem 21S, Osteohelth) for 10 minutes (Fig 2) and packed into and/or
loaded onto the highly absorbed

alveolar ridge up to the level ofthe adjacent alveolar crest (Fig 3).
A pre-adapted titanium mesh wasthen positioned and stabilized

Volume 33, Number 4, 2013

440

a

b

c

d
Figs 3a and 3b (a) Frontal and (b) occlusal views showing severebone resorption in the anterior maxillary region.
Figs 3c and 3d (c) Frontal and (d) occlusal views showing bone
substitute and autogenous bone particles mixed with rhPDGF-BB
and covered with the pre-adapted titanium mesh.
Fig 3e Frontal views showing the preparation of implant holes in
the augmented ridge; note that apparently solid bone-like tissue isformed.

eover the grafted region. As required, fixation screws (Jeil Medical) were used for stabilization of
the titanium mesh. The bone graft
mixture and titanium mesh werethen completely covered with across-linked resorbable collagenmembrane (Ossix Plus, Orapharma), and the wound was closedwith horizontal mattress and simple interrupted sutures using 5-0
monofilament synthetic absorbablematerial. Patients were instructed
to avoid brushing the treated site

The International Journal of Periodontics & Restorative Dentistryfor 2 weeks until suture removal,
to rinse with 0.12% chlorhexidine
gluconate twice daily, and to takeazithromycin (500 mg/day for 3days) and loxonin (180 mg/day for
7 days). Considerable care was taken to protect the augmented sites

441
from any external forces exerted by
the fixed or removable provisional
restorations during the entire healing period.

examine differences in the mean
healing time and VHAB/DD1 between the two groups using a statistical software package (SPSS,
IBM). P < .05 was considered statistically significant.

Clinical measurement and data
analysis
Histologic preparation

Cases with small areas of soft tissue dehiscence and no signs ofinfection (late exposure) underwent irrigation of the region withminocycline once per week. The
titanium mesh was left in place forat least 6 months in cases with nocomplications (nonexposure) orlate exposure. These groups underwent titanium mesh removal
and simultaneous implant placement when satisfactory ridge augmentation was observed. On both
GBR and reentry surgeries, the following parameters were acquired
using a University of North Carolina 15-mm periodontal probe (UNC
15, Hu-Friedy): DD1, the depth of
the bone defect, which was the
distance from the deepest pointof the defect to the most coronalhole of the titanium mesh at the
intraoral trial of the titanium mesh
(Fig 2b); DD2, the depth from the
top of the augmented bone to thetitanium mesh by measuring theprobe through the corresponding
hole of the titanium mesh at thesecond surgery for mesh removal;
VHAB, the vertical height of theaugmented bone calculated bysubtracting DD2 from DD1; andVHAB/DD1, the percentage ofaugmented bone height calculatedby dividing VHAB by DD1. The
Mann-Whitney U test was used toSurplus augmented tissue obtained as a result of bone contouring for implant placement
was used as a biopsy sample forhistologic evaluation, with the patients’ agreement, and was takenfrom the most coronal portion of
the augmentation site just below
the titanium mesh from three patients in the nonexposure group.
Samples were fixed in 10% neutral
buffered formalin and decalcified
in 5% formic acid for 6 weeks. Decalcified samples were dehydrated
with ascending grades of ethanol
and embedded in paraffin wax.
Histologic sections were cut with amicrotome (3.5-μm serial sections)in the sagittal direction, stainedwith hematoxylin-eosin, and analyzed histologically under a lightmicroscope.

Results
Clinical measurement

Of the 19 patients, 17 exhibitedprimary closure of the soft tissue over the augmentation sites
without any complications during
the entire healing period (nonexposure group) (Figs 2 and 3).
These 17 cases underwent implant

placement simultaneously with removal of the titanium mesh. The
maximum and minimum depthof the bone defect in these patients was 15.0 mm and 2.3 mm,
respectively. Vertical formation of
new bone tissue up to the heightequivalent to that of the adjacentbone was observed in 11 patientsin the nonexposure group. The
mean healing period before titanium mesh removal was 8.0 ± 1.4
months. In the majority of patients,
the site undergoing GBR was the
maxillary anterior region (Table 1).
Mean DD1 was 10.0 ± 3.8 mm,
and mean VHAB was 8.6 ± 4.0 mm
in all patients and 8.8 ± 4.2 mm in
the nonexposure patients. Mean
VHAB/DD1 was 85.8% ± 25.6% in
all patients and 87.3% ± 25.6% in
the nonexposure patients.
One patient exhibited exposure of the titanium mesh througha small wound dehiscence late in
the healing period (late exposure);
however, there were no signs ofinfection. This site had a 7.3-mm
alveolar defect and was in the region of the maxillary central incisors. A substantial volume of newbone that was sufficient for implant
placement without any additionalbone augmentation was observedin this patient (Figs 4a and 4b). A
large wound dehiscence with mild
wound infection occurred in one
patient 4 weeks after surgery in the
maxillary left lateral incisor region
that had a 11.5-mm bone defect(early exposure). This necessitated
immediate removal of the titanium
mesh. After thorough irrigation
with minocycline and saline, theflap was sutured without removing

Volume 33, Number 4, 2013

442

Table 1The distribution and number of sites subjected to GBR, DD1, healing period until theremoval of the titanium mesh, VHAB, and VHAB/DD1 for all patients
No. of patients
Maxillary
Total Anterior Molar

Mean ± SD

Mandibular
Anterior Molar

Age (y)DD1(mm)

Healingtime (mo)

VHAB
(mm)

VHAB/
DD1 (%)

Nonexposure

17

8

4

2

3

49.5 ± 15.1

9.8 ± 3.8

8.0 ± 1.5

8.8 ± 4.2

87.3 ± 25.0

Exposure

2

2

0

0

0

55.5 ± 6.4

11.1 ± 5.4

7.8 ± 0.7

7.2 ± 0.2

73.4 ± 37.7

Total

19

10

4

2

3

50.2 ± 14.4

10.0 ± 3.8

8.0 ± 1.4

8.6 ± 4.0

85.8 ± 25.6

SD = standard deviation; DD1 = depth of bone defect; VHAB = vertical height of the augmented bone; VHAB/DD1 = percentage of augmented bone.

Fig 4a Slight exposure of the titanium mesh through the gingival
flaps in the late exposure patient.

the underlying granulation tissue.
Seven months after removal of thetitanium mesh, approximately 7
mm of vertical bone augmentation
was observed. One patient in thenonexposure group experienced
occupation by connective tissue
containing Bio-Oss particles without bone formation at a site having an alveolar defect of 6.5 mm
in the mandibular anterior region.
The site was treated by a repeat
GBR procedure with the same
technique; this resulted in successful vertical bone augmentation
sufficient for implant placement 6
months after surgery.

Fig 4b Favorable and substantial bone regeneration in the late
exposure patient.

The number of patients witha median DD1 of > 8.5 mm and< 8.5 mm was 9 and 10, respectively (Table 2). The mean healing timewas 8 months for both groups, withno significant difference between
groups (P > .05). The group witha median DD1 of > 8.5 mm had amean DD1 of 13.1 ± 2.3 mm, while
the group with a median DD1 of≤ 8.5 mm had a mean DD1 of
6.5 ± 1.3 mm. In the former group,
88% of the defect height was filledwith augmented bone (VHAB/
DD1), whereas in the latter group,
80% of the defect height wasfilled with augmented bone; mean

The International Journal of Periodontics & Restorative Dentistry

VHAB in both groups was 11.0 mm
and 5.5 mm, respectively. VHAB/
DD1 was thus compatible between
the two groups.

Histology

Specimens of the regenerated
tissue after vertical ridge augmentation were subjected to hematoxylin-eosin staining (Fig 5).
Representative images viewed
under an original magnification of×4 (Fig 5b) and ×20 (Fig 5c) arepresented. Regenerated tissue inthe grafted area largely comprised

443

Table 2

DD1, healing period until the removal of the titanium mesh, VHAB, and VHAB/DD1
for all patients with DD1 > 8.5 mm and DD1 ≤ 8.5 mm
Mean ± SD
No. ofpatients

DD1 (mm)
Total

> 8.5
≤ 8.5

DD1 (mm)

Healing time(mo)

VHAB (mm)VHAB/DD1 (%)

9
10

13.1 ± 2.3
6.5 ± 1.3

8.2 ± 1.7
7.8 ± 1.2

11.4 ± 2.8
5.5 ± 2.5

88.0 ± 17.1
83.4 ± 33.7

19

10.0 ± 3.8

8.0 ± 1.4

8.6 ± 4.0

85.8 ± 25.6

SD = standard deviation; DD1 = depth of bone defect; VHAB = vertical height of the augmented bone; VHAB/DD1 = percentage of augmented bone.

1.0 mm200 µm

Fig 5a Histologic samples were obtained
from the most coronal portion of the augmentation site.

Figs 5b and 5c Histologic images of the regenerated tissue after vertical ridge augmentation; note the extensive and dense bone formation (asterisks) surrounding and filling
the gaps between the grafts (triangles), Bio-Oss particles, and autogenous bone chips(hematoxylin-eosin).

bone tissue with a small amount ofdense connective tissue (Fig 5b)
surrounding and connecting the
Bio-Oss graft particles and autogenous bone chips, which could
be identified as paler-staining
amorphous structures (Fig 5b).
Newly formed trabeculae weredensely calcified and had developed a lamellar structure withosteocytes embedded in their lacunae (Fig 5c). The graft particles
and noncellular bone-like matrix(Fig 5c) were directly attached toand partially incorporated into denovo bone.

Discussion
This retrospective case series demonstrated an overall VHAB of 8.6 ±4.0 mm. Previous clinical reports onvertical ridge augmentation with anonresorbable membrane and autogenous bone or allograft materials showed 2 to 8 mm of verticalbone augmentation.17,18 Althougha direct comparison of clinicaloutcomes between this study andprevious studies needs careful interpretation because of the differences in evaluation methods, thestaged GBR approach may enable
substantial vertical bone regen-eration equal to or surpassing thatreported in previous studies. Moreover, overall, GBR resulted in vertical bone augmentation that was> 80% of the height of the defect(VHAB/DD1) not only in defectsof ≤ 8.5 mm but also in those of agreater depth. These results indicate that this GBR procedure has
the potential to achieve assured
and complete bone regeneration
irrespective of the size of the bone
defect and deformities.
Previous clinical reports on vertical ridge augmentation with a titanium mesh for bone defects witha mean depth of approximately

Volume 33, Number 4, 2013

444
3 to 6 mm showed a high occurrence of postoperative mesh exposure (17.3% to 100% in 7 to 23
patients).3–8 In contrast, this GBR
method resulted in membrane exposure in only 2 of 19 patients (a10.5% incidence rate) even though
the bone defects treated in thisstudy were much larger (10.0 ± 3.8mm in height). More importantly,
substantial bone regeneration wasobserved in the exposure cases inthis study. In the patient with late
exposure, a bone defect that was
7.3 mm in height was almost completely filled by new bone (Figs 4a
and 4b), whereas in the early exposure patient, VHAB was 7.0 mm(47%) after removal of the titanium
mesh.
Extensive and dense new bonesurrounding and connecting thebone graft particles was observedin all histologic samples. This indicated that the GBR procedure forvertical ridge augmentation resulted in the formation of well-mineralized living lamellar bone that was
integrated with grafts, implying inherent bone homeostasis and longitudinal stability of newly formed
tissue. Previous in vitro studies
demonstrated that osteoblasts
can generate a harder, stiffer, andmore mineralized matrix on a titanium surface compared with otherbioinert materials,19,20 which indicated advantages of titanium meshin volume maintenance as well as
osteocompatibility. In addition, rhPDGF is expected to function as achemo-attractant and mitogen formesenchymal cells and for promoting angiogenesis.16,21 Despite thedebate about blocking of cellularsupply from periosteum,16,22–24 theuse of a barrier collagen membranemight help the pharmacologic effect of rhPDGF-BB on osteogenic
cellular migration and angiogenesis from bone marrow. However,some basic research showed nodirect effect of PDGF-BB on osteoblastic differentiation and boneregeneration.25,26 Determination of
the clinical benefits of rhPDGF-BB
in GBR procedures is an interesting
topic for future research, including
controlled clinical trials.

Conclusions
Within the limitations of this retrospective consecutive case series,
this GBR procedure using a crosslinked collagen membrane andtitanium mesh in conjunction with
rhPDGF-BB yielded three-dimensional alveolar bone regeneration
irrespective of the size of the bone
defect; however, long-term evaluation is required to assess the clinical outcome.

Acknowledgment
The authors express their deepest gratitude
to Dr Myron Nevins for his continued support and mentorship, Dr Takahiro Ogawa
for his mentorship in the field of titaniummaterials science, and Dr Katsutoshi Kubo,
Dr Hatsuhiko Maeda, and Dr Takeshi Ishida
for their contribution to the histologic evaluation. The authors reported no conflicts ofinterest related to this study.

The International Journal of Periodontics & Restorative Dentistry

References
1. von Arx T, Hardt N, Wallkamm B. The
TIME technique: A new method for localized alveolar ridge augmentation prior toplacement of dental implants. Int J Oral
Maxillofac Implants 1996;11:387–394.
2. Thor A. Reconstruction of the anterior
maxilla with platelet gel, autogenous
bone, and titanium mesh: A case report.
Clin Implant Dent Relat Res 2002;4:
150–155.
3. Proussaefs P, Lozada J. Use of titanium
mesh for staged localized alveolar ridge
augmentation: Clinical and histologichistomorphometric evaluation. J Oral
Implantol 2006;32:237–247.
4. Roccuzzo M, Ramieri G, Spada MC, Bianchi SD, Berrone S. Vertical alveolar
ridge augmentation by means of a titanium mesh and autogenous bone grafts.
Clin Oral Implants Res 2004;15:73–81.
5. Roccuzzo M, Ramieri G, Bunino M, Berrone S. Autogenous bone graft alone orassociated with titanium mesh for vertical alveolar ridge augmentation: A controlled clinical trial. Clin Oral Implants
Res 2007;18:286–294.
6. Proussaefs P, Lozada J, Kleinman A,
Rohrer MD, McMillan PJ. The use of titanium mesh in conjunction with autogenous bone graft and inorganic bovinebone mineral (bio-oss) for localized alveolar ridge augmentation: A human study.
Int J Periodontics Restorative Dent 2003;
23:185–195.
7. Artzi Z, Dayan D, Alpern Y, Nemcovsky
CE. Vertical ridge augmentation using xenogenic material supported by aconfigured titanium mesh: Clinicohistopathologic and histochemical study.
Int J Oral Maxillofac Implants 2003;18:
440–446.
8. Torres J, Tamimi F, Alkhraisat MH, et al.
Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge augmentation with anorganic bovine bone.
J Clin Periodontol 2010;37:943–951.
9. Simion M, Baldoni M, Rossi P, Zaffe D. A
comparative study of the effectivenessof e-PTFE membranes with and without
early exposure during the healing period. Int J Periodontics Restorative Dent
1994;14:166–180.
10. Tal H, Kozlovsky A, Artzi Z, Nemcovsky CE,
Moses O. Long-term bio-degradation ofcross-linked and non-cross-linked collagen barriers in human guided bone regeneration. Clin Oral Implants Res 2008;
19:295–302.

445
11. Friedmann A, Strietzel FP, Maretzki B,
Pitaru S, Bernimoulin JP. Observations
on a new collagen barrier membrane in
16 consecutively treated patients. Clinical and histological findings. J Periodontol 2001;72:1616–1623.
12. Ishikawa T, Salama M, Funato A, et al.
Three-dimensional bone and soft tissue
requirements for optimizing esthetic results in compromised cases with multiple
implants. Int J Periodontics Restorative
Dent 2010;30:503–511.
13. Ishikawa T. Ridge augmentation. In:
Funato A, Ishikawa T (eds). 4D Implant
Therapy: Esthetic Considerations for Soft
Tissue Management, vol 1. Chicago:
Quintessence, 2011:75–108.
14. Strietzel FP, Khongkhunthian P, Khattiya
R, Patchanee P, Reichart PA. Healing pattern of bone defects covered by different membrane types: A histologic study
in the porcine mandible. J Biomed Mater
Res Part B Appl Biomater 2006;78:35–46.
15. Lynch SE, Nixon JC, Colvin RB, Antoniades HN. Role of platelet-derived growth
factor in wound healing: Synergistic effects with other growth factors. Proc Natl
Acad Sci U S A 1987;84:7696–7700.
16. Hollinger JO, Hart CE, Hirsch SN, Lynch
S, Friedlaender GE. Recombinant humanplatelet-derived growth factor: Biology
and clinical applications. J Bone Joint
Surg Am 2008;90(suppl 1):48–54.

17. Simion M, Jovanovic SA, Tinti C, Benfenati SP. Long-term evaluation of osseointegrated implants inserted at the time
or after vertical ridge augmentation. A
retrospective study on 123 implants with
1-5 year follow-up. Clin Oral Implants
Res 2001;12:35–45.
18. Langer B, Langer L, Sullivan RM. Vertical ridge augmentation procedure using
guided bone regeneration, demineralized freeze-dried bone allograft, andminiscrews: 4- to 13-year observations
on loaded implants. Int J Periodontics
Restorative Dent 2010;30:227–235.
19. Saruwatari L, Aita H, Butz F, et al. Osteoblasts generate harder, stiffer, andmore delamination-resistant mineralized
tissue on titanium than on polystyrene,
associated with distinct tissue micro- andultrastructure. J Bone Miner Res 2005;
20:2002–2016.
20. Funato A, Yamada M, Kubo K, Maeda H,
Ogawa T. Mineralized matrix generated
by cultured osteoblasts on micro-roughened surface of titanium mesh is high in
hardness and stiffness [in Japanese]. J Japan Soc Oral Implantol 2010;23:229–238.
21. Chang PC, Seol YJ, Cirelli JA, et al.
PDGF-B gene therapy accelerates boneengineering and oral implant osseointegration. Gene Ther 2010;17:95–104.

22. Simion M, Rocchietta I, Dellavia C. Threedimensional ridge augmentation withxenograft and recombinant human platelet-derived growth factor-BB in humans:
Report of two cases. Int J Periodontics
Restorative Dent 2007;27:109–115.
23. Nevins ML, Camelo M, Schupbach P, etal. Human histologic evaluation of mineralized collagen bone substitute andrecombinant platelet-derived growth factor-BB to create bone for implant placement in extraction socket defects at 4 and6 months: A case series. Int J Periodontics Restorative Dent 2009;29:129–139.
24. Simion M, Nevins M, Rocchietta I, et al.
Vertical ridge augmentation using anequine block infused with recombinanthuman platelet-derived growth factorBB: A histologic study in a canine model.
Int J Periodontics Restorative Dent 2009;29:245–255.
25. Tokunaga A, Oya T, Ishii Y, et al. PDGF
receptor beta is a potent regulator of
mesenchymal stromal cell function.
J Bone Miner Res 2008;23:1519–1528.
26. Kumar A, Salimath BP, Stark GB, Finkenzeller G. Platelet-derived growth factor
receptor signaling is not involved in osteogenic differentiation of human mesenchymal stem cells. Tissue Eng Part A
2010;16:983–993.

Volume 33, Number 4, 2013