original article
Minimally Invasive Surgical
Techniques in Periodontal
regeneration
Pierpaolo Cortellini, MD, DDS
Accademia Toscana di Ricerca
Odontostomatologica, Firenze, Italy
- ERGOPERIO, Berne, Switzerland -
Private Practice, Firenze, Italy
Corresponding Author: Dott Pierpaolo
Cortellini, MD, DDS, Via C Botta 16 50136
Firenze, Italia; Tel. + 39 055 243950;
Fax 39 055 2478031;
E‑mail: studiocortellini@cortellini.191.it
J Evid Base Dent Pract 2012:S1:
[89-100]
1532-3382/$36.00
© 2012 Elsevier Inc. All rights reserved.
Abstract
A review of the current scientific literature was undertaken to evaluate the ef-
ficacy of minimally invasive periodontal regenerative surgery in the treatment of
periodontal defects.The impact on clinical outcomes, surgical chair-time, side effects
and patient morbidity were evaluated.
An electronic search of PUBMED database from January 1987 to December 2011
was undertaken on dental journals using the key-word “minimally invasive surgery”.
Cohort studies, retrospective studies and randomized controlled clinical trials re-
ferring to treatment of periodontal defects with at least 6 months of follow-up
were selected. Quality assessment of the selected studies was done through the
Strength of Recommendation Taxonomy Grading (SORT) System.
Ten studies (1 retrospective, 5 cohorts and 4 RCTs) were included. All the studies
consistently support the efficacy of minimally invasive surgery in the treatment of
periodontal defects in terms of clinical attachment level gain, probing pocket depth
reduction and minimal gingival recession. Six studies reporting on side effects and
patient morbidity consistently indicate very low levels of pain and discomfort dur-
ing and after surgery resulting in a reduced intake of pain-killers and very limited
interference with daily activities in the post-operative period.
Minimally invasive surgery might be considered a true reality in the field of peri-
odontal regeneration. The observed clinical improvements are consistently associ-
ated with very limited morbidity to the patient during the surgical procedure as
well as in the post-operative period. Minimally invasive surgery, however, cannot
be applied at all cases. A stepwise decisional algorithm should support clinicians in
choosing the treatment approach.
Introduction
I
n the past decade, a growing interest for more friendly, patient-oriented surgery
has urged clinical investigators to focus their interest in the development of less
invasive approaches. This interest is well depicted by the increasing number of
publications on this subject. A very rough search on PubMed introducing as the
keyword “minimally invasive surgery” with no limitations to disciplines, produced
28,386 articles, including 5322 reviews in a time frame between 1973 and 2011.
The keyword “minimally invasive dentistry” resulted in 712 articles, including 114
reviews from 1987 to 2011. The keyword “minimally invasive surgery” limited to
dentistry produced 464 articles, including 51 reviews from 1994 to 2011.
Keywords: Periodontal surgery, minimally invasive surgery, intrabony defects, periodontal regeneration
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Journal of evidence-based dental practice Special Issue—Periodontal and Implant Treatment
Surgical procedures in medicine and in dentistry have un-
dergone radical changes to reduce invasiveness; in parallel,
novel instruments and materials have been developed for the
inevitable evolution of the surgical armamentarium.
The field of periodontal surgery has been enriched with this
peculiar and innovative approach rather recently.1
Harrel and Rees1 proposed minimally invasive surgery (MIS)
with the aim to produce minimal wounds, minimal flap re-
flection, and gentle handling of the soft and hard tissues.2,3
Cortellini and Tonetti,4 with the minimally invasive surgical
technique (MIST), stressed the aspects of wound and blood
clot stability and primary wound closure for blood clot pro-
tection, further enforced with the modified minimally invasive
surgical technique (M-MIST)5 that, additionally, incorporated
also the concept of space provision for regeneration.
Minimally invasive surgery is a term that describes the use
of smaller and more precise surgical procedures that are
possible through the use of magnifying instruments, such as
operating microscopes and microsurgical instruments and
materials. In fact, the development and refinement of the MIS
approaches is greatly supported by the use of operative mi-
croscopes or magnifying lenses and of microsurgical instru-
ments and materials. Cortellini and Tonetti6,7 proposed the
use of an operative microscope in periodontal regenerative
surgery, reporting an increased capacity to manipulate the
soft tissues that resulted in an improved potential for primary
closure of the wound from an average 70% of the cases ob-
tained with regular surgery to an excellent 92% obtained
with microsurgery. Other authors reported improved out-
comes using operative microscopes in different areas of peri-
odontal surgery, from flap surgery to mucogingival surgery.8-14
Periodontal regenerative technologies are applied to improve
short- and long-term clinical outcomes of teeth periodontally
compromised, presenting with deep pockets and reduced
periodontal support. Periodontal regeneration is selected to
obtain an increase in the periodontal attachment and bone
of a severely compromised tooth, a decrease in pocket depth,
and a minimal or no increase in gingival recession. Periodontal
regeneration has been shown effective in the treatment of
1-, 2-, and 3-wall intrabony defects or combination thereof,
from very deep to very shallow, from very wide to very nar-
row.15-17 Questions of efficacy relate to the added benefit
of a treatment modality under ideal experimental conditions
(such as those of a highly controlled research center environ-
ment). Effectiveness, on the other hand, relates to the benefit
that can be achieved in a regular clinical setting where the
procedure is likely to be performed in relation to morbidity
and adverse events. Besides efficiency considerations, both
evidence for efficacy and effectiveness need to be available
to provide support for adoption of treatment approaches in
clinical practice.
Volume 12, Supplement 1
Current approaches, however, are technique sensitive and
burdened by a significant amount of clinical failures or incom-
plete success. We know today that most of the failures of re-
generative therapy have an explanation in terms of negative
patient factors, suboptimal use of surgical approaches and
materials, and insufficient clinical skill and experience of the
surgeon.18 Clinical success requires application of meticulous
diagnostic and treatment strategies.7,18
Development of periodontal regenerative medicine in the
past 25 years has followed 2 distinctive, though totally inter-
laced paths. The interest of researchers has so far focused
on regenerative materials and products on one side and on
novel surgical approaches on the other side.
The aim of this article was to review the current scientific
literature concerning minimally invasive periodontal regen-
erative surgery, highlighting its strengths and weaknesses and
to propose a clinical step-by-step approach to the treatment
of periodontal defects based on flow charts supported by
current evidence.
Minimally Invasive Surgical Techniques
The first technical proposal in periodontal regenerative sur-
gery was MIS.1,19 The authors suggested the use of MIS in
combination with bone grafting material covered with a bio-
resorbable vicryl mesh to treat isolated and multiple intrabo-
ny defects. The technique consists of an initial intrasulcular
incision around the teeth neighboring the defect, followed by
an incision between the teeth, usually on the lingual aspect,
to connect the preliminary intrasulcular ones. The papilla is
sharply dissected from the underlying bone and small buccal
and lingual flaps are carefully reflected. The connective tissue
within the osseous defect is dissected with a blade and re-
moved with curettes and ultrasonic instruments, and the root
debrided. The authors suggested finalizing root planing with
finishing burs. Root conditioning with citric acid is also sug-
gested, followed by placement of Decalcified Freeze Dried
Bone Allograft (DFDBA) mixed with tetracycline hydrochlo-
ric acid to fill or slightly overfill the defect. Overfilling should
not exceed the extent of space made available by the dissec-
tion of the connective tissue under the papilla. An unsutured
vicryl mesh is positioned to help holding the graft in place.
The flap is sutured with vertical parallel mattress sutures to
obtain primary closure.
Cortellini and Tonetti4 proposed MIST in combination with
enamel matrix derivative (EMD) to treat isolated intrabony
defects. MIST incorporates many concepts of MIS, introduc-
ing, however, some modifications. In the MIST approach, the
defect-associated interdental papilla is accessed either with
the simplified papilla preservation flap (SPPF)20 in narrow
interdental spaces or the modified papilla preservation tech-
nique (MPPT)21,22 in large interdental spaces (Figs. 1 and 2).
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 Journal of evidence-based dental practice Special Issue—Periodontal and Implant Treatment

Figure 1. (A) MIST approach to the upper right second premolar presenting with a 9-mm distal pocket.
(B) The isolated distal intrabony defect is 6 mm deep and 40° wide. (C) Access to the defect has been
gained through a very short buccal incision and a minimal flap reflection to expose the bone crest of the
3-wall intrabony defect. (D) The interdental papilla, dissected according to the principle of the MPPT, has
been raised toward the palatal side. A short vertical incision has been traced on the mesial edge of the
palatal flap to improve flap reflection. (E) A single modified internal mattress suture is positioned to seal
the wound, following the delivery of amelogenins. (F) At 1 year, the treated site presents with a 3-mm
sulcus. (G) The 1-year radiograph shows the complete resolution of the intrabony component of the
defect.
A B C D

E F G

Figure 2. (A) MIST approach to an isolated 8-mm pocket at the mesial aspect of the first lower right
molar. (B) The pocket is associated with a narrow intrabony defect 5 mm deep. (C) Three months before
regeneration, endodontic therapy has been provided to treat the periapical lesions. (D) Minimal buccal flap
reflection and the elevation of the interdental papilla according to the SPPF design provides full access
to the 3-wall intrabony component. (E) The wound has been stabilized with a single modified internal
mattress suture. No regenerative materials have been positioned in the treated site. (F) The 1-year
3-mm sulcus and the definitive crown. (G) The 1-year radiograph shows the resolution of the intrabony
component of the defect and of the periapical lesion.
A B C D

E F G

The SPPF is a diagonal incision traced as close as possible
to the buccal side of the papilla col, whereas the MPPT is a
horizontal incision traced on the buccal side of the papilla. In-
trasulcular incisions are performed from the interdental side
to the buccal and lingual sides of the teeth neighboring the
defect; tiny buccal and lingual flaps are elevated to expose the
residual bone crest. Periosteal incisions are performed only if
needed to improve flap reflection. The soft tissue is sharply
dissected from the osseous defect and debridement and
root planing are performed with a combination of mini-cu-
rettes and power air-driven instruments. EDTA is applied to
the air-dried root surface for 2 minutes, then carefully washed
away and EMD is applied on the air-dried root surface. The
suturing approach is based on the use of a single internal

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 Journal of evidence-based dental practice Special Issue—Periodontal and Implant Treatment

Figure 3. (A) Upper right lateral incisor presenting with an 8-mm mesial pocket accessed with a M-MIST
approach. (B) The radiograph shows a narrow intrabony defect. (C) The interdental incision is slightly
diagonal (SPPF-like approach). (D) A very tiny buccal flap has been raised to uncover the buccal crest. The
interdental papilla has not been elevated and the granulation tissue has been carved away from under the
interdental tissues. (E) A 6-mm combined intrabony defect is evident. (F) The surgical wound has been
sealed with a single modified internal mattress suture and an additional passing suture. No regenerative
materials have been used in this site. (G) The 1-year photograph reporting a 3-mm sulcus and no gingival
recession. (H) Radiographic resolution of the defect at 1 year.
A B C D

E F G H

Figure 4. (A) M-MIST approach to a lower left first molar presenting with a pocket 8 mm deep. (B) The
radiograph shows a deep and wide intrabony defect. (C) The small triangular buccal flap allows for the
debridement of the intrabony component of the defect. The granulation tissues have been dissected and
removed from under the interdental papilla that is left untouched. (D) Amelogenins are delivered into the
intrabony defect. (E) Single modified internal mattress suture positioned to close the interdental wound.
(F) The 1-year resolution of the treated area with a 3-mm sulcus and no gingival recession. (G) The 1-year
radiograph shows the complete resolution of the intrabony component of the defect
A B C D

E F G

modified mattress suture. Additional sutures can be applied
to further increase primary closure, when needed.
Cortellini et al23 proposed the application of a single MIS
technique to treat multiple adjacent defects. The surgi-
cal modification includes an extension of the flap to all the
teeth involved by osseous defects. The larger flap is minimally
reflected in accordance with the previously described prin-
ciples. The rest of the procedure is unmodified.
More recently, Cortellini & Tonetti5 proposed M-MIST
(Figs. 3 and 4). The surgical approach consists of a tiny inter-
dental access in which only buccal intrasulcular incisions are
performed and connected with a buccal horizontal incision
of the papilla performed as close as possible to the papilla tip.

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 Journal of evidence-based dental practice Special Issue—Periodontal and Implant Treatment
The tiny buccal triangular flap is elevated to expose the resid-
ual buccal bone crest.The papillary tissues are left untouched,
carefully preserving the supracrestal attachment apparatus to
the root cement of the crest-associated tooth. Access to the
defect is gained through the tiny buccal “window.” The soft
tissue filling the defect (ie, the so-called granulation tissue) is
sharply dissected from the papillary supracrestal connective
tissue and removed with mini-curettes. In other words, the
soft tissue filling the osseous defect is “carved” away from
under the papilla. Then the root surface is carefully debrided
with mini-curettes and power-driven air instruments avoiding
any trauma to the supracrestal fibers of the defect-associat-
ed papilla. The palatal tissues are not surgically accessed. The
suturing approach is based on the use of a single internal
modified mattress suture. Additional sutures can be applied
to further increase primary closure, when needed. M-MIST
cannot be applied to all periodontal defects.5 Its limits are
the access to the diseased root surface. Whenever a defect
extending to the lingual/palatal side of a root is difficult to
debride, the authors suggest raising the papilla and perform-
ing a MIST approach.
Technical implications
The previously cited studies propose 2 different minimally
invasive approaches to intrabony defects. The MIS1 and the
MIST4,24 include the elevation of the interdental papillary
tissues to uncover the interdental space, gaining complete
access to the intrabony defect (Figs. 1 and 2), whereas the
M-MIST5 proposes an approach in which the access to the
defect is gained through the elevation of a small buccal flap,
without elevation of the interdental papilla (Figs. 3 and 4).
The major problem to overcome in applying minimally inva-
sive surgery is the problem of visibility and manipulation of
the surgical field. This issue is clearly enhanced in the M-MIST
approach. High magnification and direct optimal illumination
can help in solving the problem. Traditionally we are taught
to raise large flaps to completely and exceedingly expose the
area of interest. In reality, our limits to defect visibility are the
residual bony walls that surround the defect. The elevation of
a flap to the edge of the residual bony walls should therefore
be sufficient to gain visibility of the defect: over-reflection of
the flaps does not increase our ability to look into the defect;
however, the minimal flap reflection narrows the angle of vi-
sion and especially the light penetration into the surgical field.
In addition, the soft tissue manipulation during instrumenta-
tion requires more care, as the flaps, not fully reflected, lay
very close to the working field. Small instruments, such as
small periosteal elevators and tiny tissue players, are manda-
tory, as well as their gentle application to soft and hard tis-
sues. Micro-blades, mini-curettes, and mini-scissors allow for
a full control of the incision, debridement, and refinement of
the surgical area, and sutures from 6-0 to 8-0 are mandatory
for the wound closure.
93
Clinical studies and outcomes
Cohort studies and randomized controlled clinical trials re-
porting outcomes on the application of minimally invasive
surgical approaches are shown in Tables 1 and 2.
Table 1 refers to studies in which the interdental papillary
tissues have been elevated to uncover the interdental space
completely (MIS and MIST). This approach is supported by a
retrospective study,25 4 cohort studies,3,4,23,24 and 2 controlled
studies.26,27
Ribeiro et al26 investigated the impact of EMD proteins on the
outcome of an MIST in the treatment of 30 intrabony defects
in 30 patients. The defects were randomly assigned to treat-
ment with MIST plus EMD or MIST alone. Significant pocket
reductions, clinical attachment gains, and minimal changes in
gingival recession were obtained at 3 and 6 months in both
groups. No clinically or statistically significant differences were
found between the 2 groups in terms of clinical and radio-
graphic evaluations at any time. The authors concluded that
the use of EMD did not provide superior benefits on the
outcome of the minimally invasive surgical approach for the
treatment of intrabony defects (Figs. 1 and 2).
Table 2 reports studies in which the access to the defect was
gained through the elevation of a small buccal flap, without
elevation of the interdental papilla. This approach is support-
ed by a cohort study5 and 2 controlled studies.28,29
Cortellini and Tonetti28 designed a 3-armed randomized
controlled clinical trial to compare the clinical efficacy of the
“modified minimally invasive surgical technique” alone ver-
sus M-MIST combined with amelogenins (EMD) and ame-
logenins plus bone mineral–derived xenograph (BMDX), in
the treatment of isolated, interdental intrabony defects. The
study was performed on 45 deep isolated intrabony defects
accessed with the M-MIST and randomly assigned to 3 ex-
perimental groups: 15 to M-MIST alone, 15 to M-MIST+EMD,
and 15 to M-MIST+EMD-BMDX. Differences between base-
line and 1 year were statistically significant in the 3 groups in
terms of probing pocket depth (PPD) reduction, as well as
in terms of clinical attachment level (CAL) gain (P > .0001).
Comparisons among the 3 groups showed no statistically sig-
nificant difference in any of the measured clinical outcomes.
In particular, CAL gains of 4.1 ± 1.4 mm were observed in
the M-MIST control group, 4.1 ± 1.2 mm in the EMD group,
and 3.7 ± 1.3 mm in the EMD+BMDX group. The percent
radiographic bone fill of the intrabony component was 77%
± 19% in the M-MIST control group, 71% ± 18% in the EMD
group, and 78% ± 27% in the EMD+BMDX group. The au-
thors concluded that the M-MIST is efficacious in the treat-
ment of intrabony defects with or without the additional use
of regenerative materials (Figs. 3 and 4).
An independent study29 reported similar outcomes with the
single-flap approach (SFA).This study evaluated the adjunctive
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 Table 1. Clinical studies in which the interdental papillary tissues have been elevated to uncover the interdental space completely

Type of study No. No. CAL PD Residual Patient

MIS / MIST (quality of evidence) Interventions pax defects gain reduction PD Δ REC outcomes
Harrel et al 199919 Retrospective MIS+DFDBA+Vycril 87 194 4.87±0.27 4.58±0.26 — — NO
(Level 3) 23pax (60)
Harrel et al 20053 Case cohort MIS+EMD+DFDBA* 16 160 3.57±1.75 3.56±1.31 3.1±0.75 0.01 NO

Volume 12, Supplement 1

(Level 2) (*if deemed indicated)
Cortellini & Tonetti 20074 Case cohort MIST+EMD 13 13 4.8±1.9 4.8±1.8 2.9±0.8 0.1±0.9 YES
(Level 2)
Cortellini & Tonetti 200724 Case cohort MIST+EMD 40 40 4.9±1.7 5.2±1.7 3±0.6 0.4±0.7 YES
(Level 2)
Cortellini et al 200823 Case cohort MIST+EMD 20 44 4.4±1.4 4.6±1.3 2.5±0.6 0.2±0.6 YES
(Level 2)
Ribeiro et al 201126 RCT MIST 15 15 2.82±1.19* 3.55±0.88* 3.57±0.81* 0.54±0.58* NO
(Level 1) MIST+EMD 14 14 3.02±1.94* 3.56±2.07* 3.53±1.12* 0.46±0.87*
Ribeiro et al 201127 RCT MIST 14 14 2.85±1.19* 3.51±0.90* 3.56±0.84* 0.48±0.51* YES
(Level 1) MINST (RPL) 13 13 2.56±1.12* 3.13±0.67* 3.21±0.85* 0.45±0.46*

EMD, enamel matrix derivative; MIS, minimally invasive surgery; MIST, minimally invasive surgical technique; MINST, minimally invasive nonsurgical technique (RPL with the aid of a microscope).
DFDBA, Decalcified Freeze Dried Bone Allograft

94
*No statistical difference.

Table 2. Clinical studies in which the access to the defect was gained through the elevation of a small buccal flap, without elevation of the
interdental papilla

Type of study No. No. CAL PD Residual Patient

M-MIST / SFA (quality of evidence) Interventions pax defects gain reduction PD Δ REC outcomes
Cortellini & Tonetti 20095 Case cohort M-MIST+EMD 15 15 4.5±1.4 4.6±1.5 3.07±0.6 0.07±0.3 YES
(Level 2)
Cortellini & Tonetti 201128 RCT M-MIST 15 15 4.1±1.4* 4.4±1.6* 3.1±0.6* 0.3±0.6* YES
(Level 1) M-MIST+EMD 15 15 4.1±1.2* 4.4±1.2* 3.4±0.6* 0.3±0.5*
Journal of evidence-based dental practice Special Issue—Periodontal and Implant Treatment

M-MIST+EMD+BioOss 15 15 3.7±1.3* 4.0±1.3* 3.3±0.6* 0.3±0.7*

Trombelli et al 201029 RCT SFA 12 12 4.4±1.5* 5.3±1.5* 3.3±0.6* 0.8±0.8* NO
(Level 1) SFA+HA+GTR 12 12 4.7±2.5* 5.3±2.4* 3.8±1.3* 0.4±1.4*

CAL, clinical attachment; GTR, resorbable collagen membrane; HA, hydroxyapatite; M-MIST, modified minimally invasive surgical technique; PD, probing depth; REC, recession; SFA, single-flap approach.
*No statistical difference.
 Journal of evidence-based dental practice Special Issue—Periodontal and Implant Treatment
effect of hydroxyapatite (HA) biomaterial protected with a
resorbable collagen membrane (GTR) in the management
of intraosseous periodontal defects accessed with SFA com-
pared with SFA alone. Twenty-four intraosseous defects in
24 patients were randomly allocated to treatment with SFA
or SFA + HA/GTR. There were no statistically significant or
clinical differences in clinical attachment gain (4.7 ± 2.5 versus
4.4 ± 1.5 mm), probing depth reduction (5.3 ± 2.4 versus 5.3
± 1.5 mm), or gingival recession increase (0.4 ± 1.4 versus
0.8 ± 0.8 mm) between the SFA + HA/GTR and SFA groups.
The authors concluded that SFA with and without HA/GTR
seems to be a valuable minimally invasive approach in the
treatment of deep intraosseous periodontal defects.
Interestingly, the reported randomized clinical trials per-
formed using minimally invasive approaches (with or without
papilla elevation) report no differences in terms of clinical
outcomes between the minimally invasive control flap ap-
proach and the test in which a regenerative material/product
was introduced under the flap. The reported outcomes raise
a series of hypotheses that focus on the intrinsic healing po-
tential of a wound when ideal conditions are provided with
the surgical approach. In other words, the outcomes of these
studies challenge clinicians with the possibility to obtain sub-
stantial clinical improvements without the use of products or
materials applying surgical techniques that do enhance “per
se” blood clot and wound stability. In particular, the advanced
flap design of the M-MIST greatly enhances the potential to
provide space and stability for regeneration by leaving the
interdental papillary soft tissues attached to the root surface
of the crest-associated tooth and by avoiding any palatal flap
elevation. The interdental soft tissues are the stable “roof ” of
a room where the blood fills in and forms a clot. The hanging
papilla prevents the collapse of the soft tissues, maintaining
thereby space for regeneration. The anatomic bone deficien-
cies are potentially supplemented by the peculiar flap design
that provides additional “soft tissue walls” to the missing bony
walls improving stability: walls of the “room” are the residual
bony walls, the root surface and the buccal/lingual soft tissues.
The minimal flap extension and elevation also minimizes the
damages to the vascular system, favoring the healing process
of the tiny soft tissues.
Postoperative period and local side effects
From the very beginning of the “guided tissue regeneration
era,” it was apparent the frequent occurrence of complica-
tions, in particular exposure of barriers. It amounted to almost
100% of the cases in the pre-papilla preservation techniques
period (Selvig et al 1992, Trombelli et al 1997)30-35 and was
reportedly reduced to an amount ranging from 50% to 6%
when papilla preservation flaps were adopted.7,15,18,20,21,36-41 A
consistent decrease of complications was observed when
barriers were not incorporated in the surgical procedure. In
95
particular, the adoption of amelogenins largely reduced the
prevalence of complications.16,39,42
The development of minimally invasive surgery has greatly
reduced the amount of complications and side effects in the
postoperative period.
Primary closure of the flap was reported in 100% of cases
treated with MIST and maintained in 95% of the cases at
1 week in single sites4,24 and in 100% of the cases in treat-
ment of multiple sites.23 Edema was noted in few cases.4,23,24
No postsurgical haematoma, suppuration, flap dehiscence,
presence of granulation tissue, or other complications were
reported in any of the treated sites.4,23,24 Root sensitivity was
not a frequent occurrence. It was reported at 1  week by
about 20% of the patients and rapidly decreased in the fol-
lowing weeks; at week 6, only 1 patient still reported some
root sensitivity.24 Ribeiro et al26 reported that the extent of
root hypersensitivity, and edema was very discreet and no
patients developed hematoma.
When applying the M-MIST, Cortellini & Tonetti5 reported
primary closure obtained and maintained in 100% of the
cases. In a second controlled study,28 one M-MIST/EMD/
BMDX site presented at suture removal (week 1) with a
slight discontinuity of the interdental wound. At week 2, the
gap appeared closed.
No edema, hematoma, or suppuration was noted in any of
the treated sites.5,28
Surgical and postsurgical patient morbidity
Patients treated with MIST and EMD were questioned at the
end of surgery and at week 1 about the intraoperative and
postoperative periods and reported no pain.4 Three patients
reported very limited discomfort in the first 2  days of the
first postoperative week. Seventy-seven percent of the pa-
tients described the first postoperative week as uneventful,
reporting that they had no feeling of having been surgically
treated after the second postoperative day.
In a large case cohort using MIST and EMD,24 none of the
patients declared intraoperative pain or discomfort and 70%
did not experience any postoperative pain. The subjects re-
porting pain described it as being very moderate (VAS 19 ±
10, with 0 = no pain and 100 = unbearable pain). In these
patients, pain lasted for 26 ± 17 hours, on average. Home
consumption of analgesic tablets was 1 ± 2, on average.
Twenty-three patients did not use any pain killer in addition
to the first 2 compulsory tablets that were administered
in the practice immediately after the surgery and 6 hours
later. Seven (17.5%) of the 12 patients reporting pain also
experienced some discomfort (VAS 28 ± 11, with 0 = no
discomfort and 100 = unbearable discomfort) that lasted
36 ± 17 hours, on average. Only 3 patients reported some
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 Journal of evidence-based dental practice Special Issue—Periodontal and Implant Treatment

interference with daily activities (work and sport activities)

SPPF, simplified papilla preservation flap; MPPT, modified papilla preservation technique; MIST, minimally invasive surgical technique; M-MIST, modified minimally invasive surgical technique; EMD, amelogenins;
The table reports the chair-time measured from delivery of anesthesia to completion of the regenerative surgical procedures, in minutes; the percentage of subjects reporting postoperative interference with
daily activities, discomfort and pain, as questioned at 1-week recall visit; the intensity of pain measured with a visual analogic scale (VAS); the number of pain killers taken in addition to the 2 compulsory
for 1 to 3 days.
Cortellini & Tonetti

In a second case cohort study with MIST and EMD,23 14

patients did not experience any postoperative pain. The 6
201128

subjects reporting pain described it as being very mild (VAS

M-MIST + EMD

19 ± 9). In these patients, pain lasted for 21 ± 5 hours, on

Table 3. Historical comparison among clinical studies performed with the use of conventional versus minimally invasive surgery

average. Home consumption of pain killers was 0.9 ± 1.0.

54.2±7.4

Nine patients did not use any analgesic in addition to the

0.3±0.6
13.3%
first 2 compulsory tablets. Ten patients experienced mild dis-
15

—
comfort (VAS 21 ± 10) that lasted 20 ± 9 hours, on average.
0

Only 4 patients reported some interference with daily activi-

ties (work and sport activities) for 1 to 3 days.
Cortellini et al 200724

Ribeiro et al,27 applying MIST and EMD, reported that the

extent of discomfort/pain experienced during therapy was
very limited. In addition, the extent of discomfort during the
first postoperative week was very discreet, and no patients
MIST + EMD

developed high fever or an interference with daily activities.

The quantity of analgesic medication taken by patients was
58±11

19±10
17.5%

1.1±2
7.5%

minimal (lower than 1 analgesic medication per patient).

30%
40

In a case-cohort study in which defects were treated with M-

MIST and EMD,5 none of the patients reported intraopera-
Tonetti et al 200443

tive or significant postoperative pain. Three patients report-

ed very limited discomfort in the first 2 days after surgery.
SPPF / MPPT+ EMD

Fourteen of 15 described the first postoperative week as

uneventful, reporting that they had no feeling of having been
surgically treated after the second postoperative day.
In a controlled study on the additional benefit of EMD or
4.3±4.5
80±34

28±20
29.5%
47.5%

EMD/BMDX to M-MIST alone,28 none of the patients re-

50%
83

ported having experienced intra- or postoperative pain.

Slight discomfort was reported by 3 patients of the M-MIST
SPPF / MPPT + Bioresorbable
Cortellini et al 200137

group (average VAS value 10.7 ± 2.1), by 2 patients of the M-

MIST EMD group (VAS 11.5 ± 0.7), and by 4 patients of the
M-MIST EMD/BMDX group (VAS 12.3 ± 3.1). Few patients
needed pain control medications: 3 patients from the control
group (average number of tablets 0.4 ± 0.7, maximum 2), 4
patients from the EMD group (average 0.3 ± 0.6, maximum
Bioresorbable barrier, polylactic and polyglycolic acid barrier.

2), and 4 patients from the EMD/BMDX group (average 0.5

28.1±2.5
barriers

4.1±2.5
99±46
35.7%
53.6%

± 1.0, maximum 3).

46%
56

In Table 3 are reported some surgical and postsurgical param-

eters from 4 studies. Two studies were performed applying
Subjects with postoperative discomfort

the traditional large papilla preservation flaps with bioresorb-

ones delivered at the end of surgery.

able barriers37 or amelogenins.43 The other 2 studies were

Subjects with postoperative pain

performed using the minimally invasive surgeries in combina-

Interference with daily activity

tion with amelogenins.24,28 This historical comparison clearly

evidences differences in most of the parameters among the 4
Regenerative approach

studies. Surgical chair-time was the longest when large papilla

preservation flaps and barriers were applied, shorter when
N° of pain killers
Chair time, min
No. of patients

large papilla preservation flaps were combined with amelo-

Pain intensity

genins, by far the shortest when M-MIST and amelogenins

were used. The number of subjects reporting postoperative
interference with daily activities, discomfort, and pain was

Volume 12, Supplement 1 96

 Journal of evidence-based dental practice Special Issue—Periodontal and Implant Treatment
Flow chart 1: Surgical Access
Interdental Space Edentulous Ridge
Width Next to Defect
>2mm 2mm
Crestal
MPPT SPPF
Incision
similar in the 2 papilla preservation flap studies, much re-
duced in the MIST study, very limited or none in the M-MIST
study, as well as pain intensity and consumption of pain killers
(Table 3). The reported outcomes indicate that postopera-
tive discomfort and pain apparently are not influenced by
the type of regenerative material but by the type of surgical
approach: a more friendly, shorter chair time, minimally inva-
sive surgery is associated with fewer postoperative problems.
These considerations might suggest clinicians adopt more
friendly approaches whenever possible.
Clinical Strategies
Periodontal regeneration in intrabony defects has been suc-
cessfully attempted with a variety of different regenerative
materials and surgical approaches. Controlled clinical trials
report added benefits in terms of clinical attachment level
gain as compared with open flap debridement alone.15-17,44-48
However, comparisons among some of the cited regenera-
tive approaches failed to demonstrate a clear superiority of
one of the tested materials. The existing evidence, there-
fore, does not support the choice of one superior approach
among the different regenerative strategies.
From a clinical standpoint, clear-cut differences are to be high-
lighted among the various surgical proposals. The traditional
papilla preservation flaps20,21 were designed as wide and very
mobile flaps to allow for ample access to the defects, for
perfect visibility of the surgical field, for easy allocation of bio-
materials, and for the coronal positioning of soft tissues to
cover barriers and biomaterials often overfilling the defects.
The MIS1 and the MIST,4,24 on the contrary, were designed
to reduce flap extension and mobility as much as possible,
so as to increase blood clot and wound stability and reduce
invasiveness and patient morbidity. A further development of
the surgical approach ended into the M-MIST,5,28 where only
a tiny buccal flap is elevated. It is clear that such a flap is not
designed to allow for the positioning of a barrier, but easily
allows for the use of biologicals or grafts.
97
Flow chart 2: Flap Design
Intrabony Defect
Involving 1/3 Sides of Involving 3/4 sides of
the Root the Root & Very Severe
Cleansable
from Buccal
YES NO
Extended
M-MIST MIST
Flap
A step-by-step surgical approach based on evidence and on
clinical experience has been built up to help clinicians in plan-
ning the proper regenerative approach to periodontal de-
fects. The following clinical flow charts were developed, also
taking into account the scientific contributions on surgical
and postsurgical events, such as chair time, side effects, and
postoperative pain. In other words, the idea is to apply to a
given periodontal defect the best performing procedure with
the minimum load of intra- and postoperative side effects
and morbidity.
The surgical access to the interdental papilla associated with
the intrabony defects can be selected among 3 different sur-
gical approaches (Flow chart 1. Strength of recommenda-
tion A): the SPPF,20 the MPPT,21,22 and the crestal incision.18
The SPPF is chosen whenever the width of the interdental
space is 2 mm or less, the MPPT is used at sites with an in-
terdental width greater than 2 mm, and the crestal incision is
applied next to an edentulous area.
The second surgical step (Flow chart 2. Strength of rec-
ommendation B) deals with the choice of the flap design.
Whenever a defect involves 1 or 2 sides of a root and is
cleansable from a tiny buccal window, an M-MIST is suggest-
ed.5,28 In some instances, both the interdental spaces neigh-
boring the defect-associated tooth can be accessed with the
M-MIST approach. The double surgical access allows for an
easier instrumentation of a defect involving also the palatal/
lingual side of the root. If the defect is not cleansable from
the buccal window, the interdental papilla is elevated, applying
a MIST approach.4,23,24 A large papilla preservation flap, ex-
tended to the neighboring teeth and eventually including also
September 2012
Journal of evidence-based dental practice Special Issue—Periodontal and Implant Treatment

Flow chart 3: Regenerative Strategy

Extended
M-MIST MIST
Flap

Any Defect Containing Non Containing Containing Noncontaining

Anatomy Defect Defect Defect Defect

No Barrier
Regenerative EMD EMD EMD + Graft EMD Barrier + Graft
Material EMD + Graft

a periosteal incision and/or vertical releasing incisions, will be
chosen in the presence of a very severe and deep all-around
defect, associated with ample buccal/lingual bone dehiscence,
requiring ample visibility for instrumentation and the use of
barriers, fillers, or combinations of barriers and fillers.20-22
Selection of the regenerative material is based on the defect
anatomy and on the flap design chosen to expose the defect
(Flow chart 3. Strength of recommendation A). If an M-MIST
approach is applied, amelogenins or no regenerative materi-
als are the elective choices.28 If a MIST is applied, amelogenins
can be used alone in containing defects or in combination
with a filler in noncontaining defects.4,23,24,26 If a large papilla
preservation flap is elevated, stability to the area should be
provided, applying barriers or fillers or combination of barri-
ers and fillers or combination of amelogenins/growth factors
and fillers.6 Amelogenins alone are preferred in defects with
a prevalent 3-wall morphology or in well-supported 2-wall
defects. 7
Flow chart 4: Suturing Strategy
M-MIST MIST
Extended
Flap
Containing Noncontaining
Defect Defect
Single Internal
Double Internal
Mattress
Mattress
Modified
The suturing approach is chosen according to the type of
regenerative strategy applied (Flow chart 4. Strength of rec-
ommendation B). It will consist of a single internal modified
mattress suture when am M-MIST or am MIST approach is
chosen and amelogenins alone are applied.4,5,23,24,28 It will con-
sists of a combination of 2 internal mattress sutures applied
at the defect associated with the interdental area to reach
primary closure of the papilla in the absence of any tension
when a large papilla preservation flap with a periosteal in-
cision is used in association with a barrier or a graft or a
combination.7,18,20-22
The surgical procedure is preferably performed with the aid
of magnification, such as loops or an operating microscope.6-8
Microsurgical instruments and materials should be used to
complement the normal periodontal set.
Postsurgical and early home care protocols are directly de-
rived from the experiences developed by running many con-
trolled clinical trials (strength of recommendation A).22,36-40,43
An empirical protocol for the control of bacterial contam-
ination consisting of doxycycline (100 mg twice a day for
1 week), 0.12% chlorhexidine mouth rinsing 3 times per day,
and weekly prophylaxis is prescribed. Sutures are removed
after 1 week. Patients are requested to avoid normal brush-
ing, flossing, and chewing in the treated area for periods of
6 to 10  weeks. A postsurgical soft toothbrush soaked in
chlorhexidine is adopted from week 1 to gently wipe the
treated area. Nonresorbable membranes are removed after
6 weeks. Patients can resume full oral hygiene and chewing
function in the treated area 2 to 4 weeks after membrane re-
moval or when bioresorbable membranes are fully resorbed.
Patients treated with amelogenins resume full oral hygiene
after a period of 4 to 5 weeks. At the end of the “early heal-
ing phase,” patients are placed on a 3-month recall system.

Volume 12, Supplement 1 98

 Journal of evidence-based dental practice Special Issue—Periodontal and Implant Treatment
A general suggestion to avoid any invasive clinical maneuver,
such as hard subgingival instrumentation, restorative dentist-
ry, orthodontics, and additional surgery, for a period of about
9 months is also part of a strategy that is aimed at optimizing
the clinical outcomes of periodontal regeneration.
Conclusions
Minimally invasive surgery might be considered a true reality
in the field of periodontal regeneration. Cohort studies and
randomized controlled clinical trials have demonstrated its
potential to greatly improve the periodontal conditions of
sites associated with intrabony defects, proving its efficacy.
These clinical improvements are consistently associated with
very limited morbidity to the patient during the surgical pro-
cedure, as well as in the postoperative period. Chair time
required to perform such a surgery is by far shorter than the
chair time required for more conventional surgical approach-
es. Minimally invasive surgery, however, cannot be applied in
all cases. A stepwise decisional algorithm should support cli-
nicians in choosing the proper approach.
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