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“PASS” Principles for Predictable
Bone Regeneration
Hom-Lay Wang, DDS, MSD,* and Lakshmi Boyapati, BDS†
G
uided bone regeneration (GBR)
describes a surgical technique
that increases and augments al-
veolar bone volume in areas designated
for future implant placement, or around
previously placed implants. The princi-
ple of GBR is based on the principles of
guided tissue regeneration.1-4
The prin-
ciples delineated by Melcher5
described
the need for cell exclusion to enable the
healing wound to be populated by cells
thought to be more favorable for regen-
eration. In GBR, the cells that are re-
quired to repopulate the wound are
primarily osteoblasts. Osteoblasts are
responsible for laying down new alveo-
lar bone and for future bone remodeling.
By selectively excluding epithelium and
connective tissue with the use of bone
grafting and barrier materials, bone is
“guided” into the desired position.
Dahlin et al6
were the first to show that
bony defects created in rat mandibles
could be successfully closed using
guided tissue regeneration procedures.
The success and predictability of
GBR have since vastly broadened the
applicability of implant therapy. Im-
plants can now be placed in areas of
previously deficient bone volume,
with success rates reported higher than
95%.7-11
However, to ensure predict-
ability of this technique, clinical pro-
cedures should be based on sound
biologic principles. This article out-
lines the 4 major principles underlying
successful GBR (Fig. 1): primary
wound closure, angiogenesis, space
creation/maintenance, and stability of
both the initial blood clot and implant
fixture (PASS).
PRIMARY CLOSURE
The 2 basic methods of wound
healing are termed healing by primary
intention and secondary intention, re-
spectively. In healing by primary in-
tension, the edges of a wound are
placed together in virtually the same
position they held before the injury.
Secondary intention describes healing
that occurs when wound edges cannot
be closely approximated, resulting in a
wound that is slower to heal, requires
more collagen remodeling, and is
more likely to result in scar formation.
Realistically, true healing by primary
intention is often difficult to achieve.
However, primary wound closure is a
fundamental surgical principle for
GBR because it creates an environ-
ment that is undisturbed/unaltered by
outside bacterial or mechanical insult.
Passive closure of wound edges
enables the wound to heal with less
reepithelialization, collagen formation
and remodeling, wound contraction,
and overall tissue remodeling. In ad-
dition, postoperative discomfort may
be reduced as a result of less exposure
of underlying connective tissue. Most
investigators have advocated the ne-
cessity of primary closure following
implant placement to ensure predict-
able GBR outcomes,7,12-15
while others
have disputed its importance.16,17
Nonetheless, there is a consensus that
primary wound coverage should be ac-
complished whenever possible.
Examining the effect of mem-
brane exposure on bone volume gains
highlights the importance of primary
wound closure. Machtei18
performed a
metaanalysis to evaluate the effects of
membrane exposure on treatment out-
comes in guided tissue regeneration
and GBR. When looking at guided
tissue regeneration cases alone, ex-
posed membranes showed only 0.47
mm less attachment gain compared to
membranes that remained submerged.
In comparison, membrane exposure
seemed to have a significant deleteri-
ous effect on bone formation. In cases
in which the membrane remained sub-
merged, a mean 3.01 mm of new bone
*Professor and Director of Graduate Periodontics, Department
of Periodontics and Oral Medicine, School of Dentistry,
University of Michigan, Ann Arbor, MI.
†Resident, Department of Periodontics and Oral Medicine,
School of Dentistry, University of Michigan, Ann Arbor, MI.
ISSN 1056-6163/06/01501-008
Implant Dentistry
Volume 15 • Number 1
Copyright © 2006 by Lippincott Williams & Wilkins
DOI: 10.1097/01.id.0000204762.39826.0f
Guided bone regeneration is a
well-established technique used for
augmentation of deficient alveolar
ridges. Predictable regeneration re-
quires both a high level of technical
skill and a thorough understanding
of underlying principles of wound
healing. This article describes the 4
major biologic principles (i.e.,
PASS) necessary for predictable
bone regeneration: primary wound
closure to ensure undisturbed and
uninterrupted wound healing, angio-
genesis to provide necessary blood
supply and undifferentiated mesen-
chymal cells, space maintenance/
creation to facilitate adequate space
for bone ingrowth, and stability of
wound and implant to induce blood
clot formation and uneventful heal-
ing events. In addition, a novel flap
design and clinical cases using this
principle are presented. (Implant
Dent 2006;15:8–17)
Key Words: guided bone regenera-
tion, bone grafts, horizontal bone
augmentation, implants
8 “PASS” PRINCIPLES FOR PREDICTABLE BONE REGENERATION
was noted, whereas in cases with
membrane exposure, an average of
0.56 mm of new bone was noted.
Similar results of a reduced
amount of bone formation subsequent
to membrane exposure have been
reported.11,18-22
Simion et al20
exam-
ined membrane exposure in cases of
GBR at the implant placement. The
investigators found that 99.6% bone
regeneration was obtained around fix-
tures where membrane exposure did
not occur for 6-8 months following
implant placement. In contrast, only
48.6% of bone regeneration was found
when membrane exposure occurred
earlier. Other studies have examined
early versus late membrane exposure
or removal.19,23,24
It seems that if a
membrane can remain covered for a
significant period, up to 6-8 months,
bone regeneration is predictable.
Factors that impede wound heal-
ing in an otherwise healthy individual
are foreign materials, necrotic tissue,
compromised blood supply, and
wound tension. These factors may
partly explain the reduced bone forma-
tion around exposed membranes.
Other possible reasons for the reduced
amount of bone formation are contam-
ination of the membrane with oral mi-
croflora caused by an open wound.25-28
More rapid resorption of bone grafting
materials in areas of membrane expo-
sure has also been reported. Jovanovic
et al29
examined 11 patients with de-
hiscence defects on the facial aspect of
19 threaded implants. A unique
method of providing space was by
placing the membrane over the im-
plants and fixating them with the im-
plant cover screw. Primary closure
was attained, and clinical evaluation
was performed after 4 months of heal-
ing. In cases in which the membranes
remained covered, 14/19 sites with de-
hiscence showed 100% bone fill in the
space created by the membrane. How-
ever, in the areas of membrane expo-
sure, little bone regeneration occurred.
These findings have further been con-
firmed in a beagle dog model30,31
and
more recently in human beings.32
The majority of membrane expo-
sure data relate to nonresorbable mem-
branes, both reinforced and nonreinforced.
The development and widespread use of
absorbable collagen membranes may
circumvent this problem. Indeed, in
addition to a reduced risk of mem-
brane exposure,22
the reported advan-
tages of these membranes are a lack of
need for second stage surgery and
physiologically favorable properties
of the membranes themselves, such as
hemostatic, chemotactic, and cell ad-
hesion functions.33-35
Advantages of collagen mem-
branes include their hemostatic func-
tion by platelet aggregation, which
facilitates early clot formation and
wound stabilization. Both early clot
formation and wound stabilization are
considered essential for successful re-
generation.36
Collagen also possesses
a chemotactic function for fibroblasts
that assists in cell migration to pro-
mote primary wound closure.37
Colla-
gen membranes are also effective in
inhibiting epithelial migration and
promoting new connective tissue
attachment.38-42
Predictable treatment
outcomes have been shown using
absorbable collagen membranes in
conjunction with bone mineral as a
supporting and space maintaining
device.43-45
In a series of 2 reports on local-
ized ridge augmentation using GBR,
Buser et al46,47
advocated primary soft
tissue healing, to avoid membrane ex-
posure, by using a lateral incision
technique. Other techniques that have
been advocated in an effort to gain
tension-free primary wound closure
include a buccal rotational flap,48
coronally positioned palatal sliding
flap,49
split palatal rotated flap,50
and,
more recently, a palatal advanced
flap.15
Together, the aforementioned
studies highlight the importance of
primary wound closure. Correct flap
design, tension-free flap approxima-
tion, and postoperative care of the
wound site are keys to achieving, and
maintaining, primary closure. Flaps
should be carefully designed and exe-
cuted to ensure passive closure with-
out tension on the wound margins.
Collagen membranes, with their che-
motactic function, may facilitate pri-
mary wound coverage, even after
membrane exposure.42
ANGIOGENESIS
Wound healing around implants is
similar to wound healing events in
other parts of the oral cavity, with
several important exceptions. In par-
ticular, bone regeneration progresses
in a sequence that closely parallels its
normal formation.51
The surface of the
implant provides a platform on which
an initial blood clot may form. The
addition of bone grafting materials and
membranes, in accordance with the
principles of GBR, serves to create
space and mediate osteogenesis via
potential release of bone morphoge-
netic proteins. Following implant place-
ment, the first 24 hours are characterized
by formation of a blood clot around im-
plant and in the space created by mem-
branes and bone grafting material. The
initial blood clot is removed by neutro-
phils and macrophages, and initial for-
mation of granulation tissue begins
within the next days and weeks. The
granulation tissue is rich in blood ves-
sels, and it is these vessels that are key
to osteoid formation and subsequent
mineralization to woven bone.52
Pri-
marily deposited woven bone will be
Fig. 1. Principles of successful GBR.
IMPLANT DENTISTRY / VOLUME 15, NUMBER 1 2006 9
converted into mature lamellar bone
by secondary remodeling.53
There is an intimate relationship
between newly formed blood vessels
and de novo bone formation.54
It has
been shown that between 6 and 9
months are needed to fill completely
the wound space, initially filled with
blood clot, then with new bone.55
Buser et al47
found that introducing
cortical perforations (i.e., intra-bone
marrow penetration) allowed migra-
tion of cells with angiogenic and os-
teogenic potential. Nonetheless, some
studies have showed that bone regen-
eration can occur even from a nonin-
jured cortical layer.56,57
Future studies
in this area are certainly encouraged.
The concept of a regional accel-
eratory phenomenon was introduced
several decades ago.58-61
Melcher and
Dryer62
also emphasized the impor-
tance of the blood clot in healing of
bony defects. Several potential advan-
tages of decortication exist. Providing
communication with marrow spaces
may enhance revascularization. Growth
factors, such as platelet derived growth
factor, and bone morphogenetic proteins
can be released to enhance periodontal
regeneration63
and peri-implant bone
formation.64
Osteogenic cells important
to bone healing can be derived from 3
main sources: the periosteum, en-
dosteum, and undifferentiated pluripo-
tential mesenchymal cells. The marrow
provides a rich source of these undiffer-
entiated cells that can be transformed
into osteoblasts and osteoclasts. In ad-
dition, the perforations through the
cortical bone provide a mechanical in-
terlock with the newly regenerated
bone. It has even been suggested that
the cortical plate may act as a temporary
hindrance for access of desirable cells
and tissue components from the marrow
because resorption of the cortical bone
has to take place before access to bone
forming components is achieved.65
Beneficial effects of regional ac-
celeratory phenomenon have been re-
ported in several animal studies.52,66-68
Larger perforations have been associ-
ated with a shorter time to obtain bone
fill but without any differences in the
total amount of new bone formed.68
Misch69
has advocated the use of both
buccal and lingual decortication to en-
hance bony healing 2-10 times higher
than normal. However, conflicting re-
ports regarding the beneficial effect of
regional acceleratory phenomenon
have also been reported.65,70,71
Lun-
dgren et al65
used a rabbit calvarial
model to evaluate the effects of decor-
tication. There were 2 titanium cylin-
ders with titanium lids inserted in the
skulls of 8 rabbits. In each animal, the
test side had the outer layer of cortical
bone removed, while the control side
was left with an intact cortex. Block
section and histology performed at 3
months in all animals revealed no dif-
ference in total amount of augmented
tissue (75.5% compared to 71.2%) or
the augmented mineralized bone tissue
(17.8% compared to 16.0%). Together,
the aforementioned literature shows the
need for adequate blood supply and an-
giogenesis for bone regeneration to oc-
cur. Although, to date, no consensus has
been established on the beneficial effect
of cortical perforation.
SPACE CREATION/MAINTENANCE
Providing adequate space for bone
regeneration is a fundamental princi-
ple of GBR. Space is needed to ensure
the proliferation of bone forming cells
while excluding unwanted epithelial
and connective tissue cells. For exam-
ple, in areas of natural space mainte-
nance, such as after the placement of
immediate implants, there is evidence
to suggest that the addition of bone
grafting materials and membranes has
no beneficial effect over no mem-
brane/no graft control sites.50,72,73
A
consensus has yet to be formed regard-
ing the need for the use of barrier
materials and/or bone grafts around
immediately placed implants.74-78
It
may be that assuming the critical
jumping distance has not been ex-
ceeded, the space formed between the
extraction socket and implant fixture
provides an ideal environment for
clot stabilization and subsequent
osteogenesis.79,80
Various animal studies have
proved that by excluding the epithe-
lium and connective tissue, a secluded
space is thereby created, allowing
slowly migrating osteoblast cells to
populate the wound, resulting in en-
hanced bone formation.4,6,57
In a clin-
ical and histomorphometric study in a
canine model, Oh et al31
used a beagle
dog model to compare the effects of 2
collagen membranes (i.e., BioGide;
Osteohealth Co., Shirley, NY, and Bio-
Mend Extend; Zimmer Dental Inc.,
Carlsbad, CA) on GBR in surgically
created buccal implant dehiscence de-
fects. Membrane exposure occurred at
9 of 15 sites and was associated with
poorer regenerative outcomes. In ad-
dition, a pattern of membrane collapse
in most of the exposed sites (8 of 9)
was associated with less regeneration.
The investigators concluded that space
maintenance and membrane coverage
were the 2 most important factors af-
fecting GBR using bioabsorbable col-
lagen membranes.
Reinforced membranes allow
space maintenance by preventing
membrane collapse that may occur
from pressure of overlying tissues. A
titanium mesh incorporated into the
membrane also improves the strength
of the membrane and allows adaptabil-
ity to the shape of the osseous defect.
Jovanovic et al81
used a canine model
and compared 3 treatment groups in
terms of bone regeneration. Group 1
had a titanium-reinforced membrane,
group 2 had a standard expanded poly-
tetrafluoroethylene membrane, and
group 3 was a control and had no
membrane. A marked gain of alveolar
bone volume, resulting in complete
supracrestal regeneration, was noted
in both expanded polytetrafluoroethyl-
ene groups (1.82 and 1.9 mm) com-
pared to only 0.53 mm achieved in the
control group. Several other studies
have compared the use of reinforced
nonresorbable and absorbable mem-
branes using various bone grafting
materials.22,43,82-84
From the available
literature, it can be concluded that
when a significant volume of bone is
required for implant placement, the
use of reinforced membranes or addi-
tional bone grafts is more beneficial.
When higher amounts of bone re-
generation are required, space making
with a barrier membrane is critical. As
mentioned previously, absorbable mem-
branes have various beneficial proper-
ties. However, a major challenge of using
an absorbable membrane alone is mem-
brane collapse that may be caused by
the overlying soft tissue pressure. Var-
ious techniques have been developed
to overcome this challenge. Using
coronally advanced flaps, placing
bone grafting materials under the
10 “PASS” PRINCIPLES FOR PREDICTABLE BONE REGENERATION
membrane, or using other methods of
mechanical support such as screws,
pins, or internal membrane frame-
works have all been evaluated with
positive results.85,86
Several case re-
ports and clinical studies were per-
formed in the early 1990s to develop a
predictable surgical protocol that
would enable the maintenance of a
secluded space that could be occu-
pied by cells with an osteogenic
potential.2,46,51,84,87
Whether the use of bone graft ma-
terial has any additional use other than
space maintenance is debatable.88
Mellonig et al83
reported results from
human cases in a delayed implant with
simultaneous GBR technique. There
were 3 treatment groups compared
(i.e., bioabsorbable membrane with
decalcified freeze-dried bone allograft
[DFDBA], expanded polytetrafluoro-
ethylene with DFDBA, and bioabsorb-
able membrane alone) in nonspace
making buccal dehiscence type defects.
Comparable percent of bone-to-implant
contact and amount of new bone vol-
ume, both in height and width, were
observed in both groups using DFDBA.
However, the control membrane-only
group had a less favorable outcome,
which the investigators attributed to lack
of space making characteristics and sub-
sequent membrane collapse.83
Similar results were shown using
a bioabsorbable membrane alone in a
monkey model,89
or using a Teflon
(DuPont Co., Wilmington, DE) mem-
brane alone in a rat model.90
In
contrast, when a stiff, dome-shaped
bioabsorbable membrane was used in
a rabbit calvaria, no difference in the
amount of regenerated bone was found
between the membrane alone group
and the membrane with bone graft
group.91
The literature seems to suggest
that the major role of bone grafting ma-
terial is space creation/maintenance.
Osteogenic and/or osteoconductive
properties of various bone grafts may
also likely play a minor role.
STABILITY
The role of a barrier membrane is
twofold. In addition to excluding un-
wanted cells, it also acts to stabilize the
blood clot.56,57,84,87,91,92
The importance
of initial clot adhesion and wound sta-
bilization is critical in wound heal-
ing.84,87,93,94
It is understood that when
the initial blood clot formation and
wound stability, as well as initial im-
plant stability, are achieved, a predict-
able wound healing sequence will occur.
This sequence will ensure predictable
bone formation. The initial blood clot
is a rich source of cytokines (e.g.,
interleukin-1, interleukin-8, tumor ne-
crosis factor), growth factors (e.g., plate-
let derived growth factor, insulin-like
growth factor, fibroblast growth factor),
and signaling molecules that recruit
clearing cells to the wound site. Platelet
derived growth factor in particular is a
potent mitogen and chemoattractant for
neutrophils and monocytes.95
The blood
clot serves as the precursor of initial
highly vascular granulation tissue. The
granulation tissue is then the site of ini-
tial intramembranous bone formation
and remodeling.51
In addition to clot stabilization,
primary stability of the implant fixture
is a key to successful regeneration and
long-term implant survival.96-98
The
lack of primary stability leads to
micromotion at the bone to implant
interface, which leads to fibrous en-
capsulation of the implant.99
Some
investigators have even advocated en-
gaging 2 cortical layers whenever pos-
sible to enhance initial stability.100,101
Resonance frequency analysis is a
novel method that may be used to as-
sess implant stability. In this tech-
nique, a transducer is attached to the
implant fixture and excited over a de-
fined frequency range. There are 2
factors that determine the resulting
resonance frequency measurement:
the degree of stability at the implant-
bone interface and the level of the
bone surrounding the transducer.102-106
Using resonance frequency analysis,
Meredith et al102
examined 56 im-
plants during their first year of inser-
tion in 9 patients. The resonance
frequency increased from 7473 to
7915 Hz on average after 8 months.
There were 2 implant failures (failure
to integrate) characterized by lower
resonance frequency readings. How-
ever, its usage in detecting implant
stability during or following GBR re-
mains to be addressed.
Clinical Case and Technique
Fig. 2 illustrates the use of an absorb-
able collagen membrane with human
mineralized bone allograft to augment
a horizontal ridge defect in conjunc-
tion with implant placement.
Technique
• Baseline information analysis
(Figs. 2A and 2B): A preoperative
clinical and radiographic evalua-
tion is needed to assess the need
for bone augmentation during im-
plant placement.
• Initial incision (Fig. 2C): An at-
tempt is always made to locate the
initial incision away from the de-
fect site so that closure is not
directly over the defect site. Ver-
tical releasing incisions, either fol-
lowing the mucogingival junction
or extending beyond mucogingival
junction, are used whenever indi-
cated. Mucogingival junction inci-
sion is a beveled vertical incision
dropped toward the buccal aspect,
with a wider base down to the
mucogingival junction. This inci-
sion is continued along the mu-
cogingival junction until adequate
visualization of the surgical site is
attained. The primary purpose of
this flap is to provide a wide base
of blood supply and minimize the
scar tissue formation because the
scar formed is likely to be hidden
by the natural mucogingival junc-
tion. This effect is more predict-
able to achieve in patients with a
wide band of keratinized gingiva.
• Reflection (Fig. 2D): A full thick-
ness mucoperiosteal flap is re-
flected 2-3 mm beyond the
margins of the defect. Traction is
then placed on the flap, and an
incision is made through the peri-
osteum. The reflection is then
continued by blunt dissection,
creating a split thickness flap that
can be repositioned tension free
over the area to be treated, and
primary closure be obtained. Sev-
eral periosteal scorings within the
buccal alveolar mucosa are also
performed to allow easy segmental
flap advancement, without placing
excessive tension on the flap base.
Usually, each periosteal scoring al-
lows 2-3-mm flap advancement.
• De´bridement (Fig. 2E): Granula-
tion tissue is completely removed
to help stop bleeding and allow
careful inspection of the defect.
IMPLANT DENTISTRY / VOLUME 15, NUMBER 1 2006 11
Implant drills were performed ac-
cording to manufacturer’s recom-
mended protocol. In addition,
drilling was based upon the prefab-
ricated surgical guides that consider
proper esthetic profile (Fig. 2F).
Fig. 2G shows implant placement
in a proper position with an obvious
horizontal ridge deficiency.
• Removal of epithelium: Where
appropriate, as in treatment of
defects associated with existing
implants, epithelium should be re-
moved from the inner surface of
the flap using a sharp curette or
diamond bur. The implant surface
should then be detoxified with ap-
propriate agents (e.g., 50 mg/mL
tetracycline for 3 minutes).
• Fitting the membrane: Collagen
membrane is trimmed and fitted
so that it extends 2-3 mm beyond
the margins of the defect in all
directions. Usually, the collagen
membrane is hydrated in sterile
saline or sterile water for 5-10
minutes before use, to improve
handling (malleability), however,
this is not mandatory.
• Fitting the flap: The flap is
checked and trimmed if necessary
to ensure that primary tension-
free closure is possible.
Fig. 2. Case No. 2. Augmentation of horizontal ridge defect in conjunction with implant placement. A, Preoperative view showing inadequate
ridge width and height. B, Presurgical radiograph illustrated potential apical lesion. C, Initial incisions depict 2 divergent vertical releasing
incisions. D, Surgical view showing ridge defects with granulomatous tissues. E, Area was de´ brided to the bare bone. F, Initial implant drill
following the surgical guide to indicate ideal buccolingual location. G, Implant placement with horizontal ridge deficiency. H, Intra-bone marrow
penetration using half-round bur. I, Sandwich bone augmentation. First layer of bone graft aimed at promoting better bone to implant contact
(human mineralized cancellous bone allograft, Puros; Zimmer Dental Inc.). J, Sandwich bone augmentation. Second layer of bone graft aimed
at creating/maintaining space (human mineralized bone cortical allograft, Puros) was used for barrier support and space creation, both
horizontally and vertically. K, Sandwich bone augmentation. Outer layer used for barrier support and space creation, both horizontally and
vertically (collagen membrane, BioMend Extend). L, Suture with 4-0 and 5-0 Vicryl suture (primary coverage with passive flap tension). M,
Four-week healing indicated uneventful healing. N, Reentry at 6 months showing new bone formation.
12 “PASS” PRINCIPLES FOR PREDICTABLE BONE REGENERATION
• Cortical perforations (Fig. 2H):
Cortical perforations are made
with a half-round bur to create
bleeding at the defect site and al-
low egress of progenitor cells.
• Bone replacement graft placement
(Figs. 2I and 2J): Graft material (e.g.,
mineralized bone allograft) is
placed at the defect site to support
the tented membrane. Tenting
screw(s) can also be used for this
purpose, either alone or in con-
junction with graft material(s).
• Membrane placement (Fig. 2K):
The membrane is then adapted at
the defect site. If the membrane is
stable, no attempt is made to fix
it. However, if the membrane is
not stable, then pins, bone screws,
or tacks may be needed to assist
the membrane stability.
• Closing (Fig. 2L): The surgical
site is closed with Vicryl (Ethi-
con, Inc., Johnson & Johnson,
Somerville, NJ), Teflon, or silk
suture with passive tension.
POSTOPERATIVE CARE
Antibiotic (e.g., Amoxicillin 2
g/day for 10 days) can be prescribed
for the patient. The patient is placed
on warm saltwater rinses for the first
2-3 weeks to encourage normal flap
healing without disturbing migrating
cells. Chlorhexidine gluconate 0.12%
(i.e., Peridex௡; Zila Pharmaceuticals,
Inc., Phoenix, AZ)or Periogard௡
(Colgate-Palmolive, New York, NY)
mouthrinse will then be used for the
next 3 weeks to facilitate plaque con-
trol. Sutures are removed at 10-14
days. The surgical site should be
checked every 2 weeks for a period of
2 months (Fig. 2M). Final result is
usually assessed at the implant uncov-
ering, typically 4-6 months after initial
surgery (Fig. 2N).
CONCLUSIONS
GBR can be a very predictable
treatment modality in the partially or
fully edentulous implant patient. The
success of the technique is based on
several biologically supported princi-
ples, such as PASS: primary wound
closure to ensure undisturbed and un-
interrupted wound healing, angiogen-
esis to provide necessary blood supply
and undifferentiated mesenchymal
cells, space maintenance/creation to
facilitate adequate space for bone in-
growth, and stability of wound and
implant to induce blood clot formation
and uneventful healing events. This
article has reviewed the biologic foun-
dation that is essential for successful
GBR. In addition, the technique in-
volved in this principle was clearly
illustrated.
Disclosure
The authors do not have any finan-
cial interests, either directly or indi-
rectly, in the products listed in the study.
ACKNOWLEDGMENTS
This study was partially supported
by the University of Michigan, Peri-
odontal Graduate Student Research
Fund.
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Reprint requests and correspondence to:
Hom-Lay Wang, DDS, MSD
Professor and Director of Graduate
Periodontics
Department of Periodontics and Oral Medicine
University of Michigan School of Dentistry
1011 North University Avenue
Ann Arbor, MI 48109-1078
Tel: (734) 763-3383
Fax: (734) 936-0374
E-mail: homlay@umich.edu
Abstract Translations [German, Spanish, Portugese, Japanese]
AUTOR(EN): Hom-Lay Wang, DDS, MSD*,
Lakshmi Boyapati, BDS**. *Professor und
Leiter des Graduiertenkollegs fu¨r Orthodon-
tie, Abteilung fu¨r Orthodontie und Oralmedi-
zin, zahnmedizinische Fakulta¨t, Universita¨t
von Michigan, Ann Arbot, MI, USA. **Assis-
tenzarzt, Abteilung fu¨r Orthodontie und
Oralmedizin, zahnmedizinische Fakulta¨t, Uni-
versita¨t von Michigan, Ann Arbot, MI, USA.
Schriftverkehr: Dr. Hom-Lay Wang, Professor
und Leiter des Graduiertenkollegs fu¨r Orth-
odontie (Professor and Director of Graduate
Periodontics), Abteilung fu¨r Orthodontie und
Oralmedizin (Department of Periodontics and
Oral Medicine), zahnmedizinische Fakulta¨t
der Universita¨t von Michigan (University of
Michigan School of Dentistry), 1011 North
University Avenue, Ann Arbor, Michigan
48109-1078, USA. Telefon: (734) 763-3383,
Fax: (734) 936-0374. eMail: homlay@umich.
edu
“PASS”-Prinzipien fu¨r eine vorhersagbar erfolgreiche Knochengewebsregeneration
ABSTRACT: Die geleitete Knochengewebswiederherstellung stellt eine eingefu¨hrte
Methode zur Anreicherung unzureichender Alveolarleisten dar. Eine vorhersagbare gute
Regeneration bedarf sowohl der gro␤en technischen Fa¨higkeiten wie auch eines pro-
funden Kenntnisstandes bezu¨glich der einer erfolgreichen Wundheilung zu Grunde lieg-
enden Prinzipien. Die vorliegende Arbeit beschreibt die vier wesentlichen biologischen
Prinzipien (d.h. PASS), die fu¨r eine vorhersagbar gute Knochenregeneration erforderlich
sind. Hierzu geho¨ren: der prima¨re Wundverschluss zur Gewa¨hrleistung einer ungesto¨rten
und ununterbrochenen Wundheilung; Gefa¨␤bildung zur Bereitstellung eines aus-
reichenden Blutzuflusses sowie unvera¨nderte Mesenchymalzellen; Raumerhaltung oder
-schaffung, um den entsprechenden Platz fu¨r Neuknochenbildung bereit zu stellen; und
Wund- sowie Implantatstabilita¨t zur Vermeidung von Blutgerinnselbildung und unerwu¨n-
schten Begleiterscheinungen bei der Heilung. Au␤erdem werden in der Abhandlung eine
neuartige Lappenkonstruktion sowie klinische Fa¨lle, die dieses Prinzip praktisch zur
Anwendung gebracht haben, vorgestellt.
SCHLU¨ SSELWO¨ RTER: Geleitete Knochengewebswiederherstellung, Knochentrans-
plantat, horizontale Knochengewebsanreicherung, Implantate
AUTOR(ES): Hom-Lay Wang, DDS, MSD*,
Lakshmi Boyapati, BDS**. *Profesor y Direc-
tor de Periodo´ntica Graduada, Departamento
de Periodo´ntica y Medicina Oral, Facultad de
Odontologı´a, Universidad de Michigan, Ann Ar-
bor, MI, EE.UU. **Residente, Departamento de
Periodo´ntica y Medicina Oral, Facultad de Od-
ontologı´a, Universidad de Michigan, Ann Arbor,
MI, EE.UU. Correspondencia a: Dr. Hom-Lay
Wang, Professor and Director of Graduate Pe-
riodontics, Departament of Periodontics and
Oral Medicine, University of Michigan School of
Dentistry, 1011 North University Avenue, Ann
Arbor, MI 48109-1078, U.S.A. Tele´fono: (734)
763-3383 Fax: (734) 936-0374. Direccio´n
electro´nica:
Los principios “PASS” para la regeneracio´n pronosticable del hueso
ABSTRACTO: La regeneracio´n guiada del hueso es una te´cnica bien establecida para
aumentar crestas alveolares deficientes. La regeneracio´n pronosticable requiere un alto
nivel de aptitud te´cnica y un completo entendimiento de los principios de curacio´n de una
herida. Esta manuscrito describe los cuatro principios biolo´gicos principales (PASS)
necesarios para la regeneracio´n pronosticable del hueso; cierre de la herida principal para
asegurar una curacio´n de la herida sin problemas y sin interrupciones; angioge´nesis para
proporcionar el suministro necesario de sangre y ce´lulas mesenquimales indiferenciadas;
mantenimiento/creacio´n del espacio para facilitar un espacio adecuado para el crecimiento
del hueso; y estabilidad para la herida y el implante para inducir la formacio´n de un
coa´gulo sanguı´neo y una curacio´n sin dificultades. Adema´s, se presentan un disen˜o nuevo de
la aleta y casos clı´nicos que utilizan este principio.
PALABRAS CLAVES: GBR; regeneracio´n guiada del hueso; injertos de hueso; aumento
horizontal del hueso, implantes.
16 “PASS” PRINCIPLES FOR PREDICTABLE BONE REGENERATION
AUTOR(ES): Hom-Lay Wang, Cirurgia˜o-
Dentista, Doutor em Odontologia*, Lakshmi
Boyapati, Bacharel em Odontologia**. *Pro-
fessor e Diretor de Periodontia Graduada,
Departamento de Periodontia e Medicina
Oral, Faculdade de Odontologia, Univer-
sidade de Michigan, Ann Arbor, MI, EUA.
**Residente, Departamento de Periodontia e
Medicina Oral, Faculdade de Odontologia,
Universidade de Michigan, Ann Arbor, MI,
EUA.Correspondeˆncia para: Dr. Hom-Lay
Wang, Professor and Director of Graduate
Periodontics, Department of Periodontics and
Oral Medicine, University of Michigan School
of Dentistry, 1011 North University Avenue,
Ann Arbor, Michigan 48109-1078, USA. Tele-
fone: (734) 763-3383, Fax: (734) 936-0374.
E-mail: homlay@umich.edu
Princı´pios “PASS” para Regenerac¸a˜o O´ ssea Previsı´vel
RESUMO: A Regenerac¸a˜o O´ ssea Guiada e´ uma te´cnica consagrada usada para aumento
de rebordos alveolares deficientes. A regenerac¸a˜o previsı´vel exige tanto um alto nı´vel de
habilidade te´cnica quanto um entendimento completo dos princı´pios subjacentes da cura
de feridas. Este manuscrito descreve os quatro princı´pios biolo´gicos principais (i.e.,
PASS) necessa´rios para a regenerac¸a˜o o´ssea previsı´vel: Fechamento prima´rio da ferida
para assegurar a cura tranqu¨ila e ininterrupta de feridas; Angiogeˆnese para fornecer
suprimento necessa´rio de sangue e ce´lulas mesenquimais indiferenciadas; Manutenc¸a˜o/
criac¸a˜o de espac¸o para facilitar espac¸o adequado para crescimento para dentro do osso; e
estabilidade de ferida e implante para induzir a formac¸a˜o de coa´gulo sangu¨ı´neo e eventos
de cura tranqu¨ilos. Ale´m disso, um original design de borda e casos clı´nicos que utilizam
este princı´pio sa˜o apresentados.
PALAVRAS-CHAVE: GBR; Regenerac¸a˜o o´ssea guiada; enxertos o´sseos; aumento hor-
izontal do osso; implantes.
IMPLANT DENTISTRY / VOLUME 15, NUMBER 1 2006 17

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“PASS” Principles for Predictable Bone Regeneration

  • 1. Downloadedfromhttps://journals.lww.com/implantdentbyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3bgVFxUJOPoaiinQfgI4guV1DLx10kAAuRbaZFTkhmJc=on07/11/2020 “PASS” Principles for Predictable Bone Regeneration Hom-Lay Wang, DDS, MSD,* and Lakshmi Boyapati, BDS† G uided bone regeneration (GBR) describes a surgical technique that increases and augments al- veolar bone volume in areas designated for future implant placement, or around previously placed implants. The princi- ple of GBR is based on the principles of guided tissue regeneration.1-4 The prin- ciples delineated by Melcher5 described the need for cell exclusion to enable the healing wound to be populated by cells thought to be more favorable for regen- eration. In GBR, the cells that are re- quired to repopulate the wound are primarily osteoblasts. Osteoblasts are responsible for laying down new alveo- lar bone and for future bone remodeling. By selectively excluding epithelium and connective tissue with the use of bone grafting and barrier materials, bone is “guided” into the desired position. Dahlin et al6 were the first to show that bony defects created in rat mandibles could be successfully closed using guided tissue regeneration procedures. The success and predictability of GBR have since vastly broadened the applicability of implant therapy. Im- plants can now be placed in areas of previously deficient bone volume, with success rates reported higher than 95%.7-11 However, to ensure predict- ability of this technique, clinical pro- cedures should be based on sound biologic principles. This article out- lines the 4 major principles underlying successful GBR (Fig. 1): primary wound closure, angiogenesis, space creation/maintenance, and stability of both the initial blood clot and implant fixture (PASS). PRIMARY CLOSURE The 2 basic methods of wound healing are termed healing by primary intention and secondary intention, re- spectively. In healing by primary in- tension, the edges of a wound are placed together in virtually the same position they held before the injury. Secondary intention describes healing that occurs when wound edges cannot be closely approximated, resulting in a wound that is slower to heal, requires more collagen remodeling, and is more likely to result in scar formation. Realistically, true healing by primary intention is often difficult to achieve. However, primary wound closure is a fundamental surgical principle for GBR because it creates an environ- ment that is undisturbed/unaltered by outside bacterial or mechanical insult. Passive closure of wound edges enables the wound to heal with less reepithelialization, collagen formation and remodeling, wound contraction, and overall tissue remodeling. In ad- dition, postoperative discomfort may be reduced as a result of less exposure of underlying connective tissue. Most investigators have advocated the ne- cessity of primary closure following implant placement to ensure predict- able GBR outcomes,7,12-15 while others have disputed its importance.16,17 Nonetheless, there is a consensus that primary wound coverage should be ac- complished whenever possible. Examining the effect of mem- brane exposure on bone volume gains highlights the importance of primary wound closure. Machtei18 performed a metaanalysis to evaluate the effects of membrane exposure on treatment out- comes in guided tissue regeneration and GBR. When looking at guided tissue regeneration cases alone, ex- posed membranes showed only 0.47 mm less attachment gain compared to membranes that remained submerged. In comparison, membrane exposure seemed to have a significant deleteri- ous effect on bone formation. In cases in which the membrane remained sub- merged, a mean 3.01 mm of new bone *Professor and Director of Graduate Periodontics, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI. †Resident, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI. ISSN 1056-6163/06/01501-008 Implant Dentistry Volume 15 • Number 1 Copyright © 2006 by Lippincott Williams & Wilkins DOI: 10.1097/01.id.0000204762.39826.0f Guided bone regeneration is a well-established technique used for augmentation of deficient alveolar ridges. Predictable regeneration re- quires both a high level of technical skill and a thorough understanding of underlying principles of wound healing. This article describes the 4 major biologic principles (i.e., PASS) necessary for predictable bone regeneration: primary wound closure to ensure undisturbed and uninterrupted wound healing, angio- genesis to provide necessary blood supply and undifferentiated mesen- chymal cells, space maintenance/ creation to facilitate adequate space for bone ingrowth, and stability of wound and implant to induce blood clot formation and uneventful heal- ing events. In addition, a novel flap design and clinical cases using this principle are presented. (Implant Dent 2006;15:8–17) Key Words: guided bone regenera- tion, bone grafts, horizontal bone augmentation, implants 8 “PASS” PRINCIPLES FOR PREDICTABLE BONE REGENERATION
  • 2. was noted, whereas in cases with membrane exposure, an average of 0.56 mm of new bone was noted. Similar results of a reduced amount of bone formation subsequent to membrane exposure have been reported.11,18-22 Simion et al20 exam- ined membrane exposure in cases of GBR at the implant placement. The investigators found that 99.6% bone regeneration was obtained around fix- tures where membrane exposure did not occur for 6-8 months following implant placement. In contrast, only 48.6% of bone regeneration was found when membrane exposure occurred earlier. Other studies have examined early versus late membrane exposure or removal.19,23,24 It seems that if a membrane can remain covered for a significant period, up to 6-8 months, bone regeneration is predictable. Factors that impede wound heal- ing in an otherwise healthy individual are foreign materials, necrotic tissue, compromised blood supply, and wound tension. These factors may partly explain the reduced bone forma- tion around exposed membranes. Other possible reasons for the reduced amount of bone formation are contam- ination of the membrane with oral mi- croflora caused by an open wound.25-28 More rapid resorption of bone grafting materials in areas of membrane expo- sure has also been reported. Jovanovic et al29 examined 11 patients with de- hiscence defects on the facial aspect of 19 threaded implants. A unique method of providing space was by placing the membrane over the im- plants and fixating them with the im- plant cover screw. Primary closure was attained, and clinical evaluation was performed after 4 months of heal- ing. In cases in which the membranes remained covered, 14/19 sites with de- hiscence showed 100% bone fill in the space created by the membrane. How- ever, in the areas of membrane expo- sure, little bone regeneration occurred. These findings have further been con- firmed in a beagle dog model30,31 and more recently in human beings.32 The majority of membrane expo- sure data relate to nonresorbable mem- branes, both reinforced and nonreinforced. The development and widespread use of absorbable collagen membranes may circumvent this problem. Indeed, in addition to a reduced risk of mem- brane exposure,22 the reported advan- tages of these membranes are a lack of need for second stage surgery and physiologically favorable properties of the membranes themselves, such as hemostatic, chemotactic, and cell ad- hesion functions.33-35 Advantages of collagen mem- branes include their hemostatic func- tion by platelet aggregation, which facilitates early clot formation and wound stabilization. Both early clot formation and wound stabilization are considered essential for successful re- generation.36 Collagen also possesses a chemotactic function for fibroblasts that assists in cell migration to pro- mote primary wound closure.37 Colla- gen membranes are also effective in inhibiting epithelial migration and promoting new connective tissue attachment.38-42 Predictable treatment outcomes have been shown using absorbable collagen membranes in conjunction with bone mineral as a supporting and space maintaining device.43-45 In a series of 2 reports on local- ized ridge augmentation using GBR, Buser et al46,47 advocated primary soft tissue healing, to avoid membrane ex- posure, by using a lateral incision technique. Other techniques that have been advocated in an effort to gain tension-free primary wound closure include a buccal rotational flap,48 coronally positioned palatal sliding flap,49 split palatal rotated flap,50 and, more recently, a palatal advanced flap.15 Together, the aforementioned studies highlight the importance of primary wound closure. Correct flap design, tension-free flap approxima- tion, and postoperative care of the wound site are keys to achieving, and maintaining, primary closure. Flaps should be carefully designed and exe- cuted to ensure passive closure with- out tension on the wound margins. Collagen membranes, with their che- motactic function, may facilitate pri- mary wound coverage, even after membrane exposure.42 ANGIOGENESIS Wound healing around implants is similar to wound healing events in other parts of the oral cavity, with several important exceptions. In par- ticular, bone regeneration progresses in a sequence that closely parallels its normal formation.51 The surface of the implant provides a platform on which an initial blood clot may form. The addition of bone grafting materials and membranes, in accordance with the principles of GBR, serves to create space and mediate osteogenesis via potential release of bone morphoge- netic proteins. Following implant place- ment, the first 24 hours are characterized by formation of a blood clot around im- plant and in the space created by mem- branes and bone grafting material. The initial blood clot is removed by neutro- phils and macrophages, and initial for- mation of granulation tissue begins within the next days and weeks. The granulation tissue is rich in blood ves- sels, and it is these vessels that are key to osteoid formation and subsequent mineralization to woven bone.52 Pri- marily deposited woven bone will be Fig. 1. Principles of successful GBR. IMPLANT DENTISTRY / VOLUME 15, NUMBER 1 2006 9
  • 3. converted into mature lamellar bone by secondary remodeling.53 There is an intimate relationship between newly formed blood vessels and de novo bone formation.54 It has been shown that between 6 and 9 months are needed to fill completely the wound space, initially filled with blood clot, then with new bone.55 Buser et al47 found that introducing cortical perforations (i.e., intra-bone marrow penetration) allowed migra- tion of cells with angiogenic and os- teogenic potential. Nonetheless, some studies have showed that bone regen- eration can occur even from a nonin- jured cortical layer.56,57 Future studies in this area are certainly encouraged. The concept of a regional accel- eratory phenomenon was introduced several decades ago.58-61 Melcher and Dryer62 also emphasized the impor- tance of the blood clot in healing of bony defects. Several potential advan- tages of decortication exist. Providing communication with marrow spaces may enhance revascularization. Growth factors, such as platelet derived growth factor, and bone morphogenetic proteins can be released to enhance periodontal regeneration63 and peri-implant bone formation.64 Osteogenic cells important to bone healing can be derived from 3 main sources: the periosteum, en- dosteum, and undifferentiated pluripo- tential mesenchymal cells. The marrow provides a rich source of these undiffer- entiated cells that can be transformed into osteoblasts and osteoclasts. In ad- dition, the perforations through the cortical bone provide a mechanical in- terlock with the newly regenerated bone. It has even been suggested that the cortical plate may act as a temporary hindrance for access of desirable cells and tissue components from the marrow because resorption of the cortical bone has to take place before access to bone forming components is achieved.65 Beneficial effects of regional ac- celeratory phenomenon have been re- ported in several animal studies.52,66-68 Larger perforations have been associ- ated with a shorter time to obtain bone fill but without any differences in the total amount of new bone formed.68 Misch69 has advocated the use of both buccal and lingual decortication to en- hance bony healing 2-10 times higher than normal. However, conflicting re- ports regarding the beneficial effect of regional acceleratory phenomenon have also been reported.65,70,71 Lun- dgren et al65 used a rabbit calvarial model to evaluate the effects of decor- tication. There were 2 titanium cylin- ders with titanium lids inserted in the skulls of 8 rabbits. In each animal, the test side had the outer layer of cortical bone removed, while the control side was left with an intact cortex. Block section and histology performed at 3 months in all animals revealed no dif- ference in total amount of augmented tissue (75.5% compared to 71.2%) or the augmented mineralized bone tissue (17.8% compared to 16.0%). Together, the aforementioned literature shows the need for adequate blood supply and an- giogenesis for bone regeneration to oc- cur. Although, to date, no consensus has been established on the beneficial effect of cortical perforation. SPACE CREATION/MAINTENANCE Providing adequate space for bone regeneration is a fundamental princi- ple of GBR. Space is needed to ensure the proliferation of bone forming cells while excluding unwanted epithelial and connective tissue cells. For exam- ple, in areas of natural space mainte- nance, such as after the placement of immediate implants, there is evidence to suggest that the addition of bone grafting materials and membranes has no beneficial effect over no mem- brane/no graft control sites.50,72,73 A consensus has yet to be formed regard- ing the need for the use of barrier materials and/or bone grafts around immediately placed implants.74-78 It may be that assuming the critical jumping distance has not been ex- ceeded, the space formed between the extraction socket and implant fixture provides an ideal environment for clot stabilization and subsequent osteogenesis.79,80 Various animal studies have proved that by excluding the epithe- lium and connective tissue, a secluded space is thereby created, allowing slowly migrating osteoblast cells to populate the wound, resulting in en- hanced bone formation.4,6,57 In a clin- ical and histomorphometric study in a canine model, Oh et al31 used a beagle dog model to compare the effects of 2 collagen membranes (i.e., BioGide; Osteohealth Co., Shirley, NY, and Bio- Mend Extend; Zimmer Dental Inc., Carlsbad, CA) on GBR in surgically created buccal implant dehiscence de- fects. Membrane exposure occurred at 9 of 15 sites and was associated with poorer regenerative outcomes. In ad- dition, a pattern of membrane collapse in most of the exposed sites (8 of 9) was associated with less regeneration. The investigators concluded that space maintenance and membrane coverage were the 2 most important factors af- fecting GBR using bioabsorbable col- lagen membranes. Reinforced membranes allow space maintenance by preventing membrane collapse that may occur from pressure of overlying tissues. A titanium mesh incorporated into the membrane also improves the strength of the membrane and allows adaptabil- ity to the shape of the osseous defect. Jovanovic et al81 used a canine model and compared 3 treatment groups in terms of bone regeneration. Group 1 had a titanium-reinforced membrane, group 2 had a standard expanded poly- tetrafluoroethylene membrane, and group 3 was a control and had no membrane. A marked gain of alveolar bone volume, resulting in complete supracrestal regeneration, was noted in both expanded polytetrafluoroethyl- ene groups (1.82 and 1.9 mm) com- pared to only 0.53 mm achieved in the control group. Several other studies have compared the use of reinforced nonresorbable and absorbable mem- branes using various bone grafting materials.22,43,82-84 From the available literature, it can be concluded that when a significant volume of bone is required for implant placement, the use of reinforced membranes or addi- tional bone grafts is more beneficial. When higher amounts of bone re- generation are required, space making with a barrier membrane is critical. As mentioned previously, absorbable mem- branes have various beneficial proper- ties. However, a major challenge of using an absorbable membrane alone is mem- brane collapse that may be caused by the overlying soft tissue pressure. Var- ious techniques have been developed to overcome this challenge. Using coronally advanced flaps, placing bone grafting materials under the 10 “PASS” PRINCIPLES FOR PREDICTABLE BONE REGENERATION
  • 4. membrane, or using other methods of mechanical support such as screws, pins, or internal membrane frame- works have all been evaluated with positive results.85,86 Several case re- ports and clinical studies were per- formed in the early 1990s to develop a predictable surgical protocol that would enable the maintenance of a secluded space that could be occu- pied by cells with an osteogenic potential.2,46,51,84,87 Whether the use of bone graft ma- terial has any additional use other than space maintenance is debatable.88 Mellonig et al83 reported results from human cases in a delayed implant with simultaneous GBR technique. There were 3 treatment groups compared (i.e., bioabsorbable membrane with decalcified freeze-dried bone allograft [DFDBA], expanded polytetrafluoro- ethylene with DFDBA, and bioabsorb- able membrane alone) in nonspace making buccal dehiscence type defects. Comparable percent of bone-to-implant contact and amount of new bone vol- ume, both in height and width, were observed in both groups using DFDBA. However, the control membrane-only group had a less favorable outcome, which the investigators attributed to lack of space making characteristics and sub- sequent membrane collapse.83 Similar results were shown using a bioabsorbable membrane alone in a monkey model,89 or using a Teflon (DuPont Co., Wilmington, DE) mem- brane alone in a rat model.90 In contrast, when a stiff, dome-shaped bioabsorbable membrane was used in a rabbit calvaria, no difference in the amount of regenerated bone was found between the membrane alone group and the membrane with bone graft group.91 The literature seems to suggest that the major role of bone grafting ma- terial is space creation/maintenance. Osteogenic and/or osteoconductive properties of various bone grafts may also likely play a minor role. STABILITY The role of a barrier membrane is twofold. In addition to excluding un- wanted cells, it also acts to stabilize the blood clot.56,57,84,87,91,92 The importance of initial clot adhesion and wound sta- bilization is critical in wound heal- ing.84,87,93,94 It is understood that when the initial blood clot formation and wound stability, as well as initial im- plant stability, are achieved, a predict- able wound healing sequence will occur. This sequence will ensure predictable bone formation. The initial blood clot is a rich source of cytokines (e.g., interleukin-1, interleukin-8, tumor ne- crosis factor), growth factors (e.g., plate- let derived growth factor, insulin-like growth factor, fibroblast growth factor), and signaling molecules that recruit clearing cells to the wound site. Platelet derived growth factor in particular is a potent mitogen and chemoattractant for neutrophils and monocytes.95 The blood clot serves as the precursor of initial highly vascular granulation tissue. The granulation tissue is then the site of ini- tial intramembranous bone formation and remodeling.51 In addition to clot stabilization, primary stability of the implant fixture is a key to successful regeneration and long-term implant survival.96-98 The lack of primary stability leads to micromotion at the bone to implant interface, which leads to fibrous en- capsulation of the implant.99 Some investigators have even advocated en- gaging 2 cortical layers whenever pos- sible to enhance initial stability.100,101 Resonance frequency analysis is a novel method that may be used to as- sess implant stability. In this tech- nique, a transducer is attached to the implant fixture and excited over a de- fined frequency range. There are 2 factors that determine the resulting resonance frequency measurement: the degree of stability at the implant- bone interface and the level of the bone surrounding the transducer.102-106 Using resonance frequency analysis, Meredith et al102 examined 56 im- plants during their first year of inser- tion in 9 patients. The resonance frequency increased from 7473 to 7915 Hz on average after 8 months. There were 2 implant failures (failure to integrate) characterized by lower resonance frequency readings. How- ever, its usage in detecting implant stability during or following GBR re- mains to be addressed. Clinical Case and Technique Fig. 2 illustrates the use of an absorb- able collagen membrane with human mineralized bone allograft to augment a horizontal ridge defect in conjunc- tion with implant placement. Technique • Baseline information analysis (Figs. 2A and 2B): A preoperative clinical and radiographic evalua- tion is needed to assess the need for bone augmentation during im- plant placement. • Initial incision (Fig. 2C): An at- tempt is always made to locate the initial incision away from the de- fect site so that closure is not directly over the defect site. Ver- tical releasing incisions, either fol- lowing the mucogingival junction or extending beyond mucogingival junction, are used whenever indi- cated. Mucogingival junction inci- sion is a beveled vertical incision dropped toward the buccal aspect, with a wider base down to the mucogingival junction. This inci- sion is continued along the mu- cogingival junction until adequate visualization of the surgical site is attained. The primary purpose of this flap is to provide a wide base of blood supply and minimize the scar tissue formation because the scar formed is likely to be hidden by the natural mucogingival junc- tion. This effect is more predict- able to achieve in patients with a wide band of keratinized gingiva. • Reflection (Fig. 2D): A full thick- ness mucoperiosteal flap is re- flected 2-3 mm beyond the margins of the defect. Traction is then placed on the flap, and an incision is made through the peri- osteum. The reflection is then continued by blunt dissection, creating a split thickness flap that can be repositioned tension free over the area to be treated, and primary closure be obtained. Sev- eral periosteal scorings within the buccal alveolar mucosa are also performed to allow easy segmental flap advancement, without placing excessive tension on the flap base. Usually, each periosteal scoring al- lows 2-3-mm flap advancement. • De´bridement (Fig. 2E): Granula- tion tissue is completely removed to help stop bleeding and allow careful inspection of the defect. IMPLANT DENTISTRY / VOLUME 15, NUMBER 1 2006 11
  • 5. Implant drills were performed ac- cording to manufacturer’s recom- mended protocol. In addition, drilling was based upon the prefab- ricated surgical guides that consider proper esthetic profile (Fig. 2F). Fig. 2G shows implant placement in a proper position with an obvious horizontal ridge deficiency. • Removal of epithelium: Where appropriate, as in treatment of defects associated with existing implants, epithelium should be re- moved from the inner surface of the flap using a sharp curette or diamond bur. The implant surface should then be detoxified with ap- propriate agents (e.g., 50 mg/mL tetracycline for 3 minutes). • Fitting the membrane: Collagen membrane is trimmed and fitted so that it extends 2-3 mm beyond the margins of the defect in all directions. Usually, the collagen membrane is hydrated in sterile saline or sterile water for 5-10 minutes before use, to improve handling (malleability), however, this is not mandatory. • Fitting the flap: The flap is checked and trimmed if necessary to ensure that primary tension- free closure is possible. Fig. 2. Case No. 2. Augmentation of horizontal ridge defect in conjunction with implant placement. A, Preoperative view showing inadequate ridge width and height. B, Presurgical radiograph illustrated potential apical lesion. C, Initial incisions depict 2 divergent vertical releasing incisions. D, Surgical view showing ridge defects with granulomatous tissues. E, Area was de´ brided to the bare bone. F, Initial implant drill following the surgical guide to indicate ideal buccolingual location. G, Implant placement with horizontal ridge deficiency. H, Intra-bone marrow penetration using half-round bur. I, Sandwich bone augmentation. First layer of bone graft aimed at promoting better bone to implant contact (human mineralized cancellous bone allograft, Puros; Zimmer Dental Inc.). J, Sandwich bone augmentation. Second layer of bone graft aimed at creating/maintaining space (human mineralized bone cortical allograft, Puros) was used for barrier support and space creation, both horizontally and vertically. K, Sandwich bone augmentation. Outer layer used for barrier support and space creation, both horizontally and vertically (collagen membrane, BioMend Extend). L, Suture with 4-0 and 5-0 Vicryl suture (primary coverage with passive flap tension). M, Four-week healing indicated uneventful healing. N, Reentry at 6 months showing new bone formation. 12 “PASS” PRINCIPLES FOR PREDICTABLE BONE REGENERATION
  • 6. • Cortical perforations (Fig. 2H): Cortical perforations are made with a half-round bur to create bleeding at the defect site and al- low egress of progenitor cells. • Bone replacement graft placement (Figs. 2I and 2J): Graft material (e.g., mineralized bone allograft) is placed at the defect site to support the tented membrane. Tenting screw(s) can also be used for this purpose, either alone or in con- junction with graft material(s). • Membrane placement (Fig. 2K): The membrane is then adapted at the defect site. If the membrane is stable, no attempt is made to fix it. However, if the membrane is not stable, then pins, bone screws, or tacks may be needed to assist the membrane stability. • Closing (Fig. 2L): The surgical site is closed with Vicryl (Ethi- con, Inc., Johnson & Johnson, Somerville, NJ), Teflon, or silk suture with passive tension. POSTOPERATIVE CARE Antibiotic (e.g., Amoxicillin 2 g/day for 10 days) can be prescribed for the patient. The patient is placed on warm saltwater rinses for the first 2-3 weeks to encourage normal flap healing without disturbing migrating cells. Chlorhexidine gluconate 0.12% (i.e., Peridex௡; Zila Pharmaceuticals, Inc., Phoenix, AZ)or Periogard௡ (Colgate-Palmolive, New York, NY) mouthrinse will then be used for the next 3 weeks to facilitate plaque con- trol. Sutures are removed at 10-14 days. The surgical site should be checked every 2 weeks for a period of 2 months (Fig. 2M). Final result is usually assessed at the implant uncov- ering, typically 4-6 months after initial surgery (Fig. 2N). CONCLUSIONS GBR can be a very predictable treatment modality in the partially or fully edentulous implant patient. The success of the technique is based on several biologically supported princi- ples, such as PASS: primary wound closure to ensure undisturbed and un- interrupted wound healing, angiogen- esis to provide necessary blood supply and undifferentiated mesenchymal cells, space maintenance/creation to facilitate adequate space for bone in- growth, and stability of wound and implant to induce blood clot formation and uneventful healing events. This article has reviewed the biologic foun- dation that is essential for successful GBR. In addition, the technique in- volved in this principle was clearly illustrated. Disclosure The authors do not have any finan- cial interests, either directly or indi- rectly, in the products listed in the study. ACKNOWLEDGMENTS This study was partially supported by the University of Michigan, Peri- odontal Graduate Student Research Fund. REFERENCES 1. Nyman S, Karring T, Lindhe J, et al. 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  • 9. nance frequency measurements on implants in the edentulous and partially dentate maxilla. Clin Oral Implants Res. 1997;8:226-233. 105. Friberg B, Sennerby L, Meredith N, et al. A comparison between cutting torque and resonance frequency measure- ments of maxillary implants. A 20-month clinical study. Int J Oral Maxillofac Surg. 1999;28:297-303. 106. Friberg B, Sennerby L, Linden B, et al. Stability measurements of one-stage Brånemark implants during healing in man- dibles. A clinical resonance frequency analysis study. Int J Oral Maxillofac Surg. 1999;28:266-272. Reprint requests and correspondence to: Hom-Lay Wang, DDS, MSD Professor and Director of Graduate Periodontics Department of Periodontics and Oral Medicine University of Michigan School of Dentistry 1011 North University Avenue Ann Arbor, MI 48109-1078 Tel: (734) 763-3383 Fax: (734) 936-0374 E-mail: homlay@umich.edu Abstract Translations [German, Spanish, Portugese, Japanese] AUTOR(EN): Hom-Lay Wang, DDS, MSD*, Lakshmi Boyapati, BDS**. *Professor und Leiter des Graduiertenkollegs fu¨r Orthodon- tie, Abteilung fu¨r Orthodontie und Oralmedi- zin, zahnmedizinische Fakulta¨t, Universita¨t von Michigan, Ann Arbot, MI, USA. **Assis- tenzarzt, Abteilung fu¨r Orthodontie und Oralmedizin, zahnmedizinische Fakulta¨t, Uni- versita¨t von Michigan, Ann Arbot, MI, USA. Schriftverkehr: Dr. Hom-Lay Wang, Professor und Leiter des Graduiertenkollegs fu¨r Orth- odontie (Professor and Director of Graduate Periodontics), Abteilung fu¨r Orthodontie und Oralmedizin (Department of Periodontics and Oral Medicine), zahnmedizinische Fakulta¨t der Universita¨t von Michigan (University of Michigan School of Dentistry), 1011 North University Avenue, Ann Arbor, Michigan 48109-1078, USA. Telefon: (734) 763-3383, Fax: (734) 936-0374. eMail: homlay@umich. edu “PASS”-Prinzipien fu¨r eine vorhersagbar erfolgreiche Knochengewebsregeneration ABSTRACT: Die geleitete Knochengewebswiederherstellung stellt eine eingefu¨hrte Methode zur Anreicherung unzureichender Alveolarleisten dar. Eine vorhersagbare gute Regeneration bedarf sowohl der gro␤en technischen Fa¨higkeiten wie auch eines pro- funden Kenntnisstandes bezu¨glich der einer erfolgreichen Wundheilung zu Grunde lieg- enden Prinzipien. Die vorliegende Arbeit beschreibt die vier wesentlichen biologischen Prinzipien (d.h. PASS), die fu¨r eine vorhersagbar gute Knochenregeneration erforderlich sind. Hierzu geho¨ren: der prima¨re Wundverschluss zur Gewa¨hrleistung einer ungesto¨rten und ununterbrochenen Wundheilung; Gefa¨␤bildung zur Bereitstellung eines aus- reichenden Blutzuflusses sowie unvera¨nderte Mesenchymalzellen; Raumerhaltung oder -schaffung, um den entsprechenden Platz fu¨r Neuknochenbildung bereit zu stellen; und Wund- sowie Implantatstabilita¨t zur Vermeidung von Blutgerinnselbildung und unerwu¨n- schten Begleiterscheinungen bei der Heilung. Au␤erdem werden in der Abhandlung eine neuartige Lappenkonstruktion sowie klinische Fa¨lle, die dieses Prinzip praktisch zur Anwendung gebracht haben, vorgestellt. SCHLU¨ SSELWO¨ RTER: Geleitete Knochengewebswiederherstellung, Knochentrans- plantat, horizontale Knochengewebsanreicherung, Implantate AUTOR(ES): Hom-Lay Wang, DDS, MSD*, Lakshmi Boyapati, BDS**. *Profesor y Direc- tor de Periodo´ntica Graduada, Departamento de Periodo´ntica y Medicina Oral, Facultad de Odontologı´a, Universidad de Michigan, Ann Ar- bor, MI, EE.UU. **Residente, Departamento de Periodo´ntica y Medicina Oral, Facultad de Od- ontologı´a, Universidad de Michigan, Ann Arbor, MI, EE.UU. Correspondencia a: Dr. Hom-Lay Wang, Professor and Director of Graduate Pe- riodontics, Departament of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Avenue, Ann Arbor, MI 48109-1078, U.S.A. Tele´fono: (734) 763-3383 Fax: (734) 936-0374. Direccio´n electro´nica: Los principios “PASS” para la regeneracio´n pronosticable del hueso ABSTRACTO: La regeneracio´n guiada del hueso es una te´cnica bien establecida para aumentar crestas alveolares deficientes. La regeneracio´n pronosticable requiere un alto nivel de aptitud te´cnica y un completo entendimiento de los principios de curacio´n de una herida. Esta manuscrito describe los cuatro principios biolo´gicos principales (PASS) necesarios para la regeneracio´n pronosticable del hueso; cierre de la herida principal para asegurar una curacio´n de la herida sin problemas y sin interrupciones; angioge´nesis para proporcionar el suministro necesario de sangre y ce´lulas mesenquimales indiferenciadas; mantenimiento/creacio´n del espacio para facilitar un espacio adecuado para el crecimiento del hueso; y estabilidad para la herida y el implante para inducir la formacio´n de un coa´gulo sanguı´neo y una curacio´n sin dificultades. Adema´s, se presentan un disen˜o nuevo de la aleta y casos clı´nicos que utilizan este principio. PALABRAS CLAVES: GBR; regeneracio´n guiada del hueso; injertos de hueso; aumento horizontal del hueso, implantes. 16 “PASS” PRINCIPLES FOR PREDICTABLE BONE REGENERATION
  • 10. AUTOR(ES): Hom-Lay Wang, Cirurgia˜o- Dentista, Doutor em Odontologia*, Lakshmi Boyapati, Bacharel em Odontologia**. *Pro- fessor e Diretor de Periodontia Graduada, Departamento de Periodontia e Medicina Oral, Faculdade de Odontologia, Univer- sidade de Michigan, Ann Arbor, MI, EUA. **Residente, Departamento de Periodontia e Medicina Oral, Faculdade de Odontologia, Universidade de Michigan, Ann Arbor, MI, EUA.Correspondeˆncia para: Dr. Hom-Lay Wang, Professor and Director of Graduate Periodontics, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Avenue, Ann Arbor, Michigan 48109-1078, USA. Tele- fone: (734) 763-3383, Fax: (734) 936-0374. E-mail: homlay@umich.edu Princı´pios “PASS” para Regenerac¸a˜o O´ ssea Previsı´vel RESUMO: A Regenerac¸a˜o O´ ssea Guiada e´ uma te´cnica consagrada usada para aumento de rebordos alveolares deficientes. A regenerac¸a˜o previsı´vel exige tanto um alto nı´vel de habilidade te´cnica quanto um entendimento completo dos princı´pios subjacentes da cura de feridas. Este manuscrito descreve os quatro princı´pios biolo´gicos principais (i.e., PASS) necessa´rios para a regenerac¸a˜o o´ssea previsı´vel: Fechamento prima´rio da ferida para assegurar a cura tranqu¨ila e ininterrupta de feridas; Angiogeˆnese para fornecer suprimento necessa´rio de sangue e ce´lulas mesenquimais indiferenciadas; Manutenc¸a˜o/ criac¸a˜o de espac¸o para facilitar espac¸o adequado para crescimento para dentro do osso; e estabilidade de ferida e implante para induzir a formac¸a˜o de coa´gulo sangu¨ı´neo e eventos de cura tranqu¨ilos. Ale´m disso, um original design de borda e casos clı´nicos que utilizam este princı´pio sa˜o apresentados. PALAVRAS-CHAVE: GBR; Regenerac¸a˜o o´ssea guiada; enxertos o´sseos; aumento hor- izontal do osso; implantes. IMPLANT DENTISTRY / VOLUME 15, NUMBER 1 2006 17