Minimally Invasive Surgical Techniques in Periodontal ... · PDF fileof periodontal defects...

September 201289

original article

Keywords: Periodontal surgery, minimally invasive surgery, intrabony defects, periodontal regeneration

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: [email protected]

J Evid Base Dent Pract 2012:S1: [89-100]

1532-3382/$36.00

© 2012 Elsevier Inc. All rights reserved.

MInIMAlly InvASIvE SuRGIcAl TEchnIquES In PERIOdOnTAl REGEnERATIOnPierpaolo Cortellini, MD, DDS

AbstrActA 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

In 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.

90volume 12, Supplement 1

JOuRnAl OF EvIdEncE-BASEd dEnTAl PRAcTIcE SPEcIAl ISSuE—PERIOdOnTAl And IMPlAnT TREATMEnT

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 technIquesThe 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).

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.

September 201291


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.

GFE

dcBA

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.

GFE

dA B c

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

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

September 201292


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.

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

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.

hGFE

dcBA

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

GFE

dcBA

September 201293


clinical studies and outcomescohort 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

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.


JOuRnAl OF EvIdEncE-BASEd dEnTAl PRAcTIcE SPEcIAl ISSuE—PERIOdOnTAl And IMPlAnT TREATMEnTT

AB

lE

1. C

lin

ical

stu

die

s in

wh

ich

th

e i

nte

rde

nta

l p

ap

illa

ry t

issu

es

hav

e b

ee

n e

levat

ed

to

un

cove

r th

e i

nte

rde

nta

l sp

ace

co

mp

lete

ly

MIS

/ M

IST

T

yp

e o

f st

ud

y(q

ual

ity o

f e

vid

en

ce)

Inte

rve

nti

on

sN

o.

pax

No

. d

efe

cts

CA

lga

inP

Dre

du

ctio

nR

esi

du

al

PD

Δ R

ECP

atie

nt

ou

tco

me

s

har

rel e

t al

199

919R

etro

spec

tive

(lev

el 3

)M

IS+

dFd

BA+

vyc

ril87

194

4.87

±0.

2723

pax

(60)

4.58

±0.

26—

—n

O

har

rel e

t al

200

53c

ase

coho

rt(l

evel

2)

MIS

+EM

d+

dFd

BA*

(*

if de

emed

indi

cate

d)16

160

3.57

±1.

753.

56±

1.31

3.1±

0.75

0.01

nO

cor

tellin

i & To

nett

i 200

74c

ase

coho

rt(l

evel

2)

MIS

T+

EMd

1313

4.8±

1.9

4.8±

1.8

2.9±

0.8

0.1±

0.9

yES

cor

tellin

i & To

nett

i 200

724c

ase

coho

rt(l

evel

2)

MIS

T+

EMd

4040

4.9±

1.7

5.2±

1.7

3±0.

60.

4±0.

7y

ES

cor

tellin

i et

al 2

00823

cas

e co

hort

(lev

el 2

)M

IST

+EM

d20

444.

4±1.

44.

6±1.

32.

5±0.

60.

2±0.

6y

ES

Rib

eiro

et

al 2

01126

Rc

T(l

evel

1)

MIS

TM

IST

+EM

d15 14

15 142.

82±

1.19

*3.

02±

1.94

*3.

55±

0.88

*3.

56±

2.07

*3.

57±

0.81

*3.

53±

1.12

*0.

54±

0.58

*0.

46±

0.87

*n

O

Rib

eiro

et

al 2

01127

Rc

T( l

evel

1)

MIS

TM

InST

(R

Pl)

14 1314 13

2.85

±1.

19*

2.56

±1.

12*

3.51

±0.

90*

3.13

±0.

67*

3.56

±0.

84*

3.21

±0.

85*

0.48

±0.

51*

0.45

±0.

46*

yES

EMd

, ena

mel

mat

rix d

eriv

ativ

e; M

IS, m

inim

ally

inva

sive

surg

ery;

MIS

T, m

inim

ally

inva

sive

surg

ical

tec

hniq

ue; M

InST

, min

imal

ly in

vasiv

e no

nsur

gica

l tec

hniq

ue (

RPl

with

the

aid

of a

mic

rosc

ope)

. D

FDBA

, Dec

alci

fied

Free

ze D

ried

Bone

Allo

graf

t *n

o st

atist

ical

diff

eren

ce.

TA

Bl

E 2

. Cli

nic

al s

tud

ies

in w

hic

h t

he

acc

ess

to

th

e d

efe

ct w

as g

ain

ed

th

rou

gh t

he

ele

vat

ion

of

a sm

all

bu

ccal

flap

, w

ith

ou

t e

levat

ion

of

the

in

terd

en

tal

pap

illa

M-M

IST

/ S

FAT

yp

e o

f st

ud

y(q

ual

ity o

f e

vid

en

ce)

Inte

rve

nti

on

sN

o.

pax

No

. d

efe

cts

CA

lga

inP

Dre

du

ctio

nR

esi

du

al

PD

Δ R

ECP

atie

nt

ou

tco

me

s

cor

tellin

i & To

nett

i 200

95c

ase

coho

rt(l

evel

2)

M-M

IST

+EM

d15

154.

5±1.

44.

6±1.

53.

07±

0.6

0.07

±0.

3y

ES

cor

tellin

i & To

nett

i 201

128R

cT

( lev

el 1

)M

-MIS

T

M-M

IST

+EM

dM

-MIS

T+

EMd

+Bi

oOss

15 15 15

15 15 15

4.1±

1.4*

4.1±

1.2*

3.7±

1.3*

4.4±

1.6*

4.4±

1.2*

4.0±

1.3*

3.1±

0.6*

3.4±

0.6*

3.3±

0.6*

0.3±

0.6*

0.3±

0.5*

0.3±

0.7*

yES

Trom

belli

et a

l 201

029R

cT

( lev

el 1

)SF

ASF

A+

hA

+G

TR

12 1212 12

4.4±

1.5*

4.7±

2.5*

5.3±

1.5*

5.3±

2.4*

3.3±

0.6*

3.8±

1.3*

0.8±

0.8*

0.4±

1.4*

nO

CA

L, cl

inic

al a

ttac

hmen

t; G

TR

, res

orba

ble

colla

gen

mem

bran

e; H

A, h

ydro

xyap

atite

; M-M

IST,

mod

ified

min

imal

ly in

vasiv

e su

rgic

al t

echn

ique

; PD

, pro

bing

dep

th; R

EC, r

eces

sion;

SFA

, sin

gle-

flap

appr

oach

. *n

o st

atist

ical

diff

eren

ce.

September 201295


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 morbidityPatients 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

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 effectsFrom 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



interference with daily activities (work and sport activities) for 1 to 3 days.

In a second case cohort study with MIST and EMd,23 14 patients did not experience any postoperative pain. The 6 subjects reporting pain described it as being very mild (VAS 19 ± 9). In these patients, pain lasted for 21 ± 5 hours, on average. Home consumption of pain killers was 0.9 ± 1.0. nine patients did not use any analgesic in addition to the first 2 compulsory tablets. Ten patients experienced mild dis-comfort (vAS 21 ± 10) that lasted 20 ± 9 hours, on average. Only 4 patients reported some interference with daily activi-ties (work and sport activities) for 1 to 3 days.

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 developed high fever or an interference with daily activities. The quantity of analgesic medication taken by patients was minimal (lower than 1 analgesic medication per patient).

In a case-cohort study in which defects were treated with M-MIST and EMd,5 none of the patients reported intraopera-tive or significant postoperative pain. Three patients report-ed very limited discomfort in the first 2 days after surgery. 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 EMd/BMdX to M-MIST alone,28 none of the patients re-ported having experienced intra- or postoperative pain. Slight discomfort was reported by 3 patients of the M-MIST 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 2), and 4 patients from the EMd/BMdX group (average 0.5 ± 1.0, maximum 3).

In Table 3 are reported some surgical and postsurgical param-eters from 4 studies. Two studies were performed applying the traditional large papilla preservation flaps with bioresorb-able barriers37 or amelogenins.43 The other 2 studies were performed using the minimally invasive surgeries in combina-tion with amelogenins.24,28 This historical comparison clearly evidences differences in most of the parameters among the 4 studies. Surgical chair-time was the longest when large papilla preservation flaps and barriers were applied, shorter when large papilla preservation flaps were combined with amelo-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

Tab

le 3

. His

tori

cal

com

pari

son

am

on

g cl

inic

al s

tud

ies

pe

rfo

rme

d w

ith

th

e u

se o

f co

nve

nti

on

al v

ers

us

min

imal

ly i

nvas

ive

su

rge

ry

Co

rte

llin

i e

t al

20

01

37

To

ne

tti

et

al 2

00

443

Co

rte

llin

i e

t al

20

07

24

Co

rte

llin

i &

To

ne

tti

20

11

28

Reg

ener

ativ

e ap

proa

chSP

PF /

MPP

T +

Bio

reso

rbab

le

barr

iers

SPPF

/ M

PPT

+ E

Md

MIS

T +

EM

dM

-MIS

T +

EM

d

no.

of p

atie

nts

5683

4015

cha

ir tim

e, m

in99

±46

80±

3458

±11

54.2

±7.

4

Inte

rfere

nce

with

dai

ly a

ctiv

ity35

.7%

29.5

%7.

5%0

Subj

ects

with

pos

tope

rativ

e di

scom

fort

53.6

%47

.5%

17.5

%13

.3%

Subj

ects

with

pos

tope

rativ

e pa

in

46%

50%

30%

0

Pain

inte

nsity

28.1

±2.

528

±20

19±

10—

N°

of p

ain

kille

rs4.

1±2.

54.

3±4.

51.

1±2

0.3±

0.6

The

tab

le r

epor

ts t

he c

hair-

time

mea

sure

d fr

om d

eliv

ery

of a

nest

hesia

to

com

plet

ion

of t

he r

egen

erat

ive

surg

ical

pro

cedu

res,

in m

inut

es; t

he p

erce

ntag

e of

sub

ject

s re

port

ing

post

oper

ativ

e in

terfe

renc

e w

ith

daily

act

iviti

es, d

iscom

fort

and

pai

n, a

s qu

estio

ned

at 1

-wee

k re

call

visit

; the

inte

nsity

of p

ain

mea

sure

d w

ith a

visu

al a

nalo

gic

scal

e (V

AS)

; the

num

ber

of p

ain

kille

rs t

aken

in a

dditi

on t

o th

e 2

com

pulso

ry

ones

del

iver

ed a

t th

e en

d of

sur

gery

.

SPPF

, sim

plifi

ed p

apilla

pre

serv

atio

n fla

p; M

PPT,

mod

ified

pap

illa p

rese

rvat

ion

tech

niqu

e; M

IST,

min

imal

ly in

vasiv

e su

rgic

al t

echn

ique

; M-M

IST,

mod

ified

min

imal

ly in

vasiv

e su

rgic

al t

echn

ique

; EM

D, a

mel

ogen

ins;

Bior

esor

babl

e ba

rrie

r, po

lyla

ctic

and

pol

ygly

colic

aci

d ba

rrie

r.

September 201297


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

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 strategiesPeriodontal 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.

Flow chart 1: Surgical Access

Edentulous Ridge Next to Defect

Interdental Space Width

>2mm 2mm

Crestal IncisionMPPT SPPF

Flow chart 2: Flap Design

Intrabony Defect

Involving 1/3 Sides of the Root

Involving 3/4 sides of the Root & Very Severe

Cleansable from Buccal

Extended Flap

YES NO

MISTM-MIST



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.

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 3: Regenerative Strategy

M-MIST MIST Extended Flap

Containing Defect

Non Containing Defect

Any Defect Anatomy

Containing Defect

Noncontaining Defect

BarrierBarrier + GraftEMD + Graft

EMDEMD + GraftEMDNo

Regenerative Material

EMD

Flow chart 4: Suturing Strategy

M-MIST MIST Extended Flap

Containing Defect

Noncontaining Defect

Single Internal Mattress Modified

Double Internal Mattress

September 201299


11. Zuhr O, Fickl S, Wachtel H, Bolz W, Hurzeler MB. Covering of gingival recessions with a modified microsurgical tunnel technique: case report. Int J Periodontics Restorative dent 2007;27(5):457-63.

12. Fickl S, Thalmair T, Kebschull M, Böhm S, Wachtel H. Microsurgical ac-cess flap in conjunction with enamel matrix derivative for the treat-ment of intra-bony defects: a controlled clinical trial. J clin Periodontol 2009;36:784-90.

13. cortellini P, Stalpers G, Mollo A, Tonetti MS. Periodontal regeneration versus extraction and prosthetic replacement of teeth severely com-promised by attachment loss to the apex: 5-year results of an ongoing randomized clinical trial. J clin Periodontol 2011;38:915-24.

14. cortellini P, Tonetti MS , Pini Prato G. The partly epithelialized free gin-gival graft (PE-FGG) at lower incisors. A pilot study with implications for alignment of the muco-gingival junction. J Clin Periodontol 2012;39: 674-680.

15. Murphy KG, Gunsolley JC. Guided tissue regeneration for the treat-ment of periodontal intrabony and furcation defects. A systematic re-view. Ann Periodontol 2003;8:266-302.

16. Esposito M, Grusovin MG, Papanikolaou N, Coulthard P, Worthington hv. Enamel matrix derivative (Emdogain) for periodontal tissue regen-eration in intrabony defects. A cochrane Systematic Review. Eur J Oral Implantol 2009;2:247-66.

17. Needleman IG, Worthington HV, Giedrys-Leeper E, Tucker RJ. Guided tissue regeneration for periodontal infra-bony defects. cochrane data-base Syst Rev 2006;(2):cd001724.

18. cortellini P, Tonetti MS. Focus on intrabony defects: guided tissue regen-eration (GTR). Periodontology 2000 2000:22:104-32.

19. Harrel SK. A minimally invasive surgical approach for periodon-tal regeneration: surgical technique and observations. J Periodontol 1999:70:1547-57.

20. Cortellini P, Pini-Prato G, Tonetti M. The simplified papilla preservation flap. A novel surgical approach for the management of soft tissues in regenerative procedures. Int J Periodontics Rest dent 1999:19:589-99.

21. Cortellini P, Pini-Prato G, Tonetti M. The modified papilla preservation technique. A new surgical approach for interproximal regenerative pro-cedures. J Periodontol 1995;66:261-6.

22. cortellini P, Pini-Prato G, Tonetti M. Periodontal regeneration of human infrabony defects with titanium reinforced membranes. A controlled clinical trial. J Periodontol 1995;66:797-803.

23. cortellini P, M nieri, GP Pini Prato, Tonetti MS. Single minimally inva-sive surgical technique (MIST) with enamel matrix derivative (EMd) to treat multiple adjacent intrabony defects. Clinical outcomes and patient morbidity. J clin Periodontol 2008;35:605-13.

24. cortellini P, Tonetti MS. Minimally invasive surgical technique (M.I.S.T.) and enamel matrix derivative (EMd) in intrabony defects. (I) clinical outcomes and intra-operative and post-operative morbidity. J clin Peri-odontol 2007;34:1082-8.

25. Harrel SK, Nunn ME, Belling CM. Long term results of minimally invasive surgical approach for bone grafting. J Periodontol 1999:70:1558-63.

26. Ribeiro Fv, casarin Rc, Palma MA, Júnior Fh, Sallum EA, casati MZ. The role of enamel matrix derivative protein in minimally invasive surgery in treating intrabony defects in single rooted teeth: a randomized clinical trial. J Periodontol. 2011;82:522-32.

27. Ribeiro Fv, casarin Rc, Palma MA, Júnior Fh, Sallum EA, casati MZ. clinical and patient-centered outcomes after minimally invasive non-surgical or surgical approaches for the treatment of intrabony defects: a randomized clinical trial. J Periodontol 2011;82:1256-66.

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.

reFerences 1. Harrel SK, Rees TD. Granulation tissue removal in routine and mini-

mally invasive surgical procedures. compend contin Educ dent 1995;16:960-7.

2. Harrel TK, Nunn ME. Longitudinal comparison of the periodontal status of patients with moderate to severe periodontal disease receiving no treatment, non-surgical treatment, and surgical treatment utilizing indi-vidual sites for analysis. J Periodontol 2001;72:1509-19.

3. Harrel SK, Wilson TG Jr, Nunn ME. Prospective assessment of the use of enamel matrix proteins with minimally invasive surgery. J Periodontol 2005;76:380-4.

4. cortellini P, Tonetti MS. A Minimally Invasive Surgical Technique (MIST) with enamel matrix derivate in the regenerative treatment of in-trabony defects: a novel approach to limit morbidity. J clin Periodontol 2007;34:87-93.

5. Cortellini P, Tonetti MS. Improved wound stability with a modified mini-mally invasive surgical technique in the regenerative treatment of iso-lated interdental intrabony defects. J clin Periodontol 2009;36:157–63.

6. cortellini P, Tonetti MS. Microsurgical approach to periodontal regen-eration. Initial evaluation in a case cohort. J Periodontol 2001;72:559-69.

7. cortellini P, Tonetti MS. clinical performance of a regenerative strategy for intrabony defects: scientific evidence and clinical experience. J Peri-odontol 2005;76:341-50.

8. Wachtel H, Schenk G, Bohm S, Weng D, Zuhr O, Hurzeler MB. Micro-surgical access flap and enamel matrix derivative for the treatment of periodontal intrabony defects: a controlled clinical study. J clin Peri-odontol 2003;30:496–504.

9. Francetti l, del Fabbro M, calace S, Testori T, Weinstein Rl. Microsurgi-cal treatment of gingival recession: a controlled clinical study. Int J Peri-odontics Restorative dent 2005;25:181-8.

10. Burkhardt R, Lang NP. Coverage of localized gingival recessions: com-parison of micro and macrosurgical techniques. J clin Periodontol 2005;32(3):287-93.



28. cortellini P, Tonetti MS. clinical and radiographic outcomes of the mod-ified minimally invasive surgical technique with and without regenera-tive materials: a randomized-controlled trial in intra-bony defects. J clin Peridontol 2011;38:365-73.

29. Trombelli l, Simonelli A, Pramstraller M, Wikesjo UME, Farina R. Single flap approach with and without guided tissue regeneration and a hy-droxyapatite biomaterial in the management of intraosseous periodon-tal defects. J Periodontol 2010; 81:1256-63.

30. Becker W, Becker BE, Berg L, Pritchard J, Caffesse R, Rosenberg E. New attachment after treatment with root isolation procedures: report for treated class III and class II furcations and vertical osseous defects. Int J Periodontics Rest dent 1988;8:2-16.

31. cortellini P, Pini-Prato G, Baldi c, clauser c. Guided tissue regeneration with different materials. Int J Periodontics Rest dent 1990:10:136-51.

32. cortellini P, Pini-Prato G, Tonetti M. Periodontal regeneration of human infrabony defects. I. clinical measures. J Periodontol 1993;64:254-60.

33. Falk H, Laurell L, Ravald N, Teiwik A, Persson R. Guided tissue regen-eration therapy of 203 consecutively treated intrabony defects using a bioabsorbable matrix barrier. Clinical and radiographic findings. J Peri-odontol 1997:68:571-81.

34. Murphy K. Post-operative healing complications associated with Gore-tex periodontal material. Part 1. Incidence and characterization. Int J Periodontics Rest dent 1995;15:363-75.

35. Mayfield L, Söderholm G, Hallström H, Kullendorff B, Edwardsson S, Bratthall G, et al. Guided tissue regeneration for the treatment of in-traosseous defects using a bioabsorbable membrane. A controlled clini-cal study. J clin Periodontol 1998:25:585-95.

36. cortellini P, Pini-Prato G, Tonetti M. Periodontal regeneration of human intrabony defects with bioresorbable membranes. A controlled clinical trial. J Periodontol 1996:67:217-23.

37. cortellini P, Tonetti MS, lang nP, Suvan JE, Zucchelli G, vangsted T, et al. The simplified papilla preservation flap in the regenerative treatment of deep intrabony defects: clinical outcomes and postoperative morbidity. J Periodontol 2001;72:1701-12.

38. Tonetti M, cortellini P, Suvan JE, Adriaens P, Baldi c, dubravec d, et al. Generalizability of the added benefits of guided tissue regeneration in the treatment of deep intrabony defects. Evaluation in a multi-center randomized controlled clinical trial. J Periodontol 1998:69:1183-92.

39. Tonetti MS, lang nP, cortellini P, Suvan JE, Adriaens P, dubravec d, et al. Enamel matrix proteins in the regenerative therapy of deep intrabony defects. A multicenter randomized controlled clinical trial. J clin Peri-odontol 2002;29:317-25.

40. Tonetti MS, cortellini P, lang nP, Suvan JE, Adriaens P, dubravec d, et al. clinical outcomes following treatment of human intrabony defects with GTR/bone replacement material or access flap alone. A multicenter randomized controlled clinical trial. J clin Periodontol 2004;31:770-6.

41. Machtei E. The effect of membrane exposure on the outcome of regenerative procedures in humans: a meta-analysis. J Periodontol 2001;72:512-6.

42. Sanz M, Tonetti MS, Zabalegui I, Sicilia A, Blanco J, Rebelo h, et al. Treat-ment of intrabony defects with enamel matrix proteins or barrier membranes: results from a multicenter practice-based clinical trial. J Periodontol 2004;75:726-33.

43. Tonetti MS, Fourmousis I, Suvan J, cortellini P, Bragger u, lang nP; Eu-ropean Research Group on Periodontology (ERGOPERIO). healing, post-operative morbidity and patient perception of outcomes follow-ing regenerative therapy of deep intrabony defects. J clin Periodontol 2004b:31:1092-8.

44. Trombelli L, Heitz-Mayfield LJ, Needleman I, Moles D, Scabbia A. A sys-tematic review of graft materials and biological agents for periodontal intraosseous defects. J clin Periodontol 2002;29(Suppl 3):117-35.

45. Trombelli l, Farina R. clinical outcomes with bioactive agents alone or in combination with grafting or guided tissue regeneration. J clin Peri-odontol 2008;35(Suppl):117-35.

46. Giannobile WV, Somerman MJ. Growth & amelogenin-like factors in periodontal wound healing. A systematic review. Ann Periodontol 2003;8:193-204.

47. Reynolds MA, Aichelmann-Reidy ME, Branch-Mays Gl, Gunsolley Jc. The efficacy of bone replacement grafts in the treatment of periodontal osseous defects. A systematic review. Ann Periodontol 2003;8:227-65.

48. Tu Y-K, Woolston A, Faggion CM Jr. Do bone grafts or barrier mem-branes provide additional treatment effects for infrabony lesions treated with enamel matrix derivatives? A network meta-analysis of randomized-controlled trials. J clin Periodontol 2010;37:59-79.

Minimally Invasive Surgical Techniques in Periodontal ... · PDF fileof periodontal defects...

Documents

Transcript of Minimally Invasive Surgical Techniques in Periodontal ... · PDF fileof periodontal defects...