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Improved wound stability with amodified minimally invasivesurgical technique in theregenerative treatment of isolatedinterdental intrabony defects

Cortellini P, Tonetti MS. Improved wound stability with a modified minimally invasivesurgical technique in the regenerative treatment of isolated interdental intrabonydefects. J Clin Periodontol 2009; 36: 157–163. doi: 10.1111/j.1600-051X.2008.01352.

AbstractAims: This paper describes a modified surgical approach of the minimally invasivesurgical technique (modified minimally invasive surgical technique, M-MIST) andpreliminarily evaluates its applicability and clinical performances in the treatment ofisolated deep intrabony defects in combination with amelogenins.

Material and Methods: Twenty deep isolated intrabony defects in 20 patients werestudied. Fifteen were surgically accessed with the M-MIST, while in five sites, whichpresented a lingual intrabony component, the conventional MIST had to be applied.The M-MIST consisted of a buccal incision of the defect-associated papilla, accordingto the principles of the papilla preservation techniques. Only a buccal flap was raisedwhile the interdental papilla was left in situ. The granulation tissue filling the defectwas dissected and removed, leaving the interdental and palatal tissues untouched. Rootinstrumentation and application of the regenerative material were performed beforesuturing. Primary closure of the flaps was attained with a single internal modifiedmattress suture. Surgery was performed with the aid of an operating microscope andmicrosurgical instruments.

Results: The surgical chair-time of the M-MIST-treated sites (N 5 15) was56 � 8.64 min. Early wound healing was uneventful: primary wound closure wasattained and maintained in all sites. No oedema or haematoma was noted. Patients didnot report pain or discomfort. The 1-year clinical attachment level (CAL) gain was4.5 � 1.4 mm in defects 6 � 1.5 mm deep. Residual probing depths (PDs) were3.1 � 0.6 mm. A minimal increase of 0.1 � 0.3 mm in gingival recession betweenbaseline and 1 year was observed.

Conclusions: M-MIST was applicable on 15 isolated interproximal defects out of 20selected ones. It resulted in very limited patient morbidity and excellent clinicalimprovements. These outcomes should be confirmed in a larger study.

Key words: clinical trial; microsurgery;osseous defects; periodontal diseases;periodontal regeneration

Accepted for publication 23 October 2008

Conflict of interest and sources offunding statement

This study has been self-supported by theauthors and the European Research Groupon Periodontology.PC and MT have lectured for Straumann(and previously for Biora).

In the last decade, some clinical inves-tigators have focused their interest onthe development of minimally invasivesurgical approaches in periodontal sur-gery. Harrel & Rees (1995) proposed theminimally invasive surgery (MIS) withthe aim to produce minimal wounds,minimal flap reflection and gentle hand-

Pierpaolo Cortellini1,2 andMaurizio S. Tonetti2

1Private Practice, Florence, Italy; 2European

Research Group on Periodontology

(ERGOPerio), Berne, Switzerland

ling of the soft and hard tissues inperiodontal surgery (Harrel & Nunn2001, Harrel et al. 2005). Cortellini &Tonetti (2001, 2002, 2004) and Wachtelet al. (2003) tested the use of operativemicroscopes and microsurgical instru-ments to increase visual acuity andaccuracy in the application of papilla

J Clin Periodontol 2009; 36: 157–163 doi: 10.1111/j.1600-051X.2008.01352.x

157r 2009 John Wiley & Sons A/SJournal compilation r John Wiley & Sons A/S

preservation flaps in periodontal regen-eration.

Recently, a new surgical approach,the ‘‘minimally invasive surgical tech-nique (MIST)’’, has been proposed totreat isolated intrabony defects withperiodontal regeneration (Cortellini &Tonetti 2007a). The background foun-dations for this technique are the con-cepts of the (MIS, Harrel & Rees 1995)and the application of papilla preserva-tion techniques (Cortellini et al. 1995,1999) with a microsurgical approach(Cortellini & Tonetti 2001, 2005).Results from a cohort study in isolateddeep intrabony defects showed markedimprovements in terms of clinicalattachment level (CAL) gains and PDreduction, associated with very limitedgingival recession (Cortellini & Tonetti2007b). The cited study also reported avery limited patient morbidity and areduced length of the surgical procedurefollowing application of the MIST. Thesame approach was effective in thetreatment of multiple adjacent intrabonydefects (Cortellini et al. 2008).

An enhancement of this technique,the modified minimally invasive surgi-cal technique (M-MIST Fig. 1), hasbeen recently designed to further reducethe surgical invasiveness, with threemajor objectives in mind: (1) minimizethe interdental tissue tendency to col-lapse, (2) enhance the wound/soft tissuestability and (3) reduce patient morbid-ity.

The aim of the present study was todescribe the ‘‘M-MIST’’ and prelimina-rily evaluate its applicability, clinicalperformances and patient acceptance inthe treatment of isolated, interdentaldeep intrabony defects.

Material and Methods

Study population and experimental

design

Patients with advanced periodontal dis-ease, in general good health and pre-senting with at least one isolated deep,predominantly interdental intrabonydefect were considered eligible for thisstudy. Patients were included after com-pletion of cause-related therapy consist-ing of scaling and root planing,motivation and oral hygiene instruc-tions. Flap surgery for pocket elimina-tion in sites different from theexperimental ones was performed,when indicated, before the regenerative

treatment. All subjects gave informedwritten consent.

Inclusion/exclusion criteria were asfollows:

1. Patients in good general health.Patients with uncontrolled or poorlycontrolled diabetes, unstable or life-threatening conditions, or requiringantibiotic prophylaxis were excluded.

2. Defect anatomy. Presence of at leastone tooth with probing pocket depth(PPD) and CAL loss of at least 5 mmassociated with an intrabony defectof at least 3 mm involving predomi-nantly the interdental space of thetooth. Teeth that presented a detect-able buccal and/or a lingual intrab-ony component were excluded.

3. Smoking status. Only non-smokerswere included.

Fig. 1. The modified minimally invasive surgery: a representative case. (a) A 7 mm pocketdistal to the upper right cuspid is associated with 9 mm of attachment level. (b) The drawingdepicts the buccal incision to gain access to the defect without interdental and lingualincisions. (c) Clinical image of the buccal incision. (d) The minimally invasive buccal flaphas been reflected and the granulation tissue removed from under the interdental papilla.(e) A 4 mm two-wall intrabony defect is evident. The buccal wall is missing. (f) No incisionshave been performed on the palatal side. (g) An internal modified mattress suture ispositioned to close the wound. (h) Primary closure of the interdental space. (i) The internalmodified mattress suture from the lingual side. (j) At 1 year a 2 mm probing depthis associated with a 5 mm clinical attachment level. (k) Baseline radiograph. (l) 1-yearradiograph.

158 Cortellini & Tonetti

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4. Good oral hygiene. Full-mouth pla-que score (FMPS) 420%.

5. Low levels of residual infection.Full-mouth bleeding score (FMBS)420%.

6. Compliance. Only patients with opti-mal compliance, as assessed duringthe cause-related phase of therapy,were selected.

7. Endodontic status. Teeth had to bevital or properly treated with rootcanal therapy.

Three months after completion ofperiodontal therapy, baseline clinicalmeasurements were recorded. Theexperimental sites were accessed withthe M-MIST and carefully debrided.Measurements were taken during sur-gery to characterize the defect anatomy.EDTA and EMD (Emdogain, InstituteStraumann AG, Basel, Switzerland)were applied on the instrumented anddried root surfaces, and flaps weresutured with modified internal mattresssutures. Patients were enrolled in a

stringent postoperative supportive careprogramme with weekly recalls for 6weeks, and then included in a 3-monthperiodontal supportive care programmefor 1 year.

Clinical measurements at baseline and at

the 1-year follow-up visit

The following clinical parameters wereevaluated at baseline before regenera-tive therapy and at the 1-year follow-upvisit by an independent clinician.FMPSs were recorded as the percentageof total surfaces (four aspects per tooth)that revealed the presence of plaque(O’Leary 1972). Bleeding on probing(BOP) was assessed dichotomouslyand FMBSs were then calculated(Cortellini et al. 1993a)

PPD and recession of the gingivalmargin (REC) were recorded to thenearest millimetre at the deepest loca-tion of the selected interproximal site.All measurements and BOP were takenusing a pressure-sensitive manual perio-

dontal probe at 0.3 N (Brodontic probeequipped with a PCP-UNC 15 tip, Hu-Friedy, Chicago, IL, USA). CAL werecalculated as the sum of PPD and REC.The radiographic defect angle of eachdefect was measured on a periapicalradiograph, as described previously(Tonetti et al. 1993). The chair-time ofeach surgical procedure was recorded.Primary closure of the flaps was evalu-ated at completion of surgery and atweekly recalls for a period of 6 weeks,along with the potential presence/absenceof oedema and/or haematoma. Patientswere questioned about the subjectiveperception of intra-operative pain and/ordiscomfort at completion of surgery, andof post-operative pain and/or discomfort1 week after surgery (Cortellini & Tonetti2001, Tonetti et al. 2004).

Clinical characterization of the intrabony

defects

Defect morphology was characterizedintra-surgically in terms of the distancebetween the cemento-enamel junctionand the bottom of the defect (CEJ-BD)and the total depth of the intrabonycomponent of the defect (INFRA),essentially as described previously (Cor-tellini et al. 1993b). The defects weredescribed as 1-, 2-, 3-wall or combina-tion defects.

Surgical approach (M-MIST)

Flap elevation

The defect-associated interdental papillawas surgically approached either withthe simplified papilla preservation flapwhen the width of the interdental spacewas 2 mm or narrower (SPPF, Cortelliniet al. 1999) or the modified papillapreservation technique at interdentalsites wider than 2 mm (MPPT Cortelliniet al. 1995). The interdental incision(SPPF or MPPT) was extended to thebuccal aspect of the two teeth adjacentto the defect. These incisions werestrictly intra-sulcular to preserve theentire height and width of the gingiva,and their mesio-distal extension waskept at minimum (ideally, within themid-buccal area of the involved teeth)to allow the reflection of a triangularbuccal flap to expose the coronal edge ofthe buccal bone crest. The interdentalpapillary tissues were partially dissectedin a bucco-lingual and corono-apicaldirection with a microblade (micro6900, Advanced Surgical Technologies,

Fig. 1. Continued.

Improved wound stability with modified minimally invasive surgical technique 159


Sacramento, CA, USA). The microbladecut through the interdental tissues, split-ting the coronal part (basically thesupracrestal tissues) from the apicalpart (i.e. the ‘‘granulation’’ tissue fillingthe intrabony component of the defect).The micro-blade was introduced with aninclination suitable to intercept the buc-cal side of the lingual bone crest, asclose as possible to its coronal edge, toisolate the granulation tissue filling theintrabony component of the defect fromthe supra-crestal, papillary tissues. Nointerdental and/or lingual intrasulcularincisions were performed. The supra-crestal interdental tissues, therefore,remained attached to the root cementof the crest-associated tooth, continuouswith the palatal tissue, and were notdisplaced.

Defect debridement, EMD applicationand suturing technique

The granulation soft tissue was dis-sected from the buccal and interdentalbony walls with the micro-blade andcarefully removed with a sharp minicurette (Gracey, Hu-Friedy) from underthe papilla. The defect was debridedwith the combined use of mini curettesand power-driven instruments (SoniflexLux, Kavo, Germany) and the root wascarefully planed. Special care was takento reach all the parts of the exposed rootsurface and residual bony walls, partlyhidden by the non-elevated lingual andpapillary soft tissues. To allow instru-mentation, the buccal papillary flap wasslightly reflected, carefully protectedwith a periosteal elevator and frequentlyirrigated with saline. Mini-curettes andsonic instruments were also carefullyinserted through the interdental pocketof the defect-associated tooth, betweenthe preserved interdental papilla and theroot surface, to reach the root surface fordebridement. Care was taken to preventany disruption of the papillary fibrousattachment to the bone crest and to thecrest-associated root, in order to pre-serve the stability of the papilla. At theend of instrumentation, EDTA wasapplied on the root surface for 2 min.and then the defect area was carefullyrinsed with saline. Before the applica-tion of EMD, a single modified internalmattress suture was positioned at thedefect-associated interdental area (6-0or 7-0 e-PTFE Goretex, WL Gore &Associates, Flagstaff, AZ, USA). Thesuture was left loose. EMD was appliedon the rinsed and air-dried root surface.

Finally, the suture was tightened toreach primary closure of the defect-associated papilla (Cortellini & Tonetti2001, 2005, 2007a, b).

When persistent bleeding wasobserved at the end of defect/root instru-mentation, a gauze wet with saline wasgently placed into the defect for 5 min.to halt bleeding before application ofEDTA and EMD (Cortellini & Tonetti2007b, Cortellini et al. 2008).

All the surgical procedures were per-formed with the aid of an operatingmicroscope (Global Protege, St Louis,MO) at a magnification of � 4 to� 16 (Cortellini & Tonetti 2001, 2005).Microsurgical instruments were utilized,whenever needed, as a complement to thenormal periodontal set of instruments.

Sites with a lingually extendeddefect component

When the experimental defect extendedfar too much on the lingual side of theinvolved tooth, the interdental papillawas elevated along with a lingual flap toallow a proper debridement and EMDapplication at the lingual side. In thesecases, surgery was thereby completedfollowing the rules of the MIST (Cor-tellini & Tonetti 2007a, b).

Post-operative period

Post-operative pain was controlled withibuprofen. Patients received 600 mg atthe end of the surgical procedure andwere instructed to take another tablet 6 hlater. Subsequent doses were taken onlyif necessary to control pain. Patients withcontraindications to NSAIDs received500 mg acetaminophen at surgery andafter 6 h. A protocol for the control ofbacterial contamination consisting ofsystemic doxicycline (100 mg b.i.d. for1 week), 0.12% chlorhexidine mouthrinsing three times per day and weeklyprophylaxis was prescribed (Tonettiet al. 2002). Patients were requested toavoid brushing, flossing and chewing inthe treated area for a periods of 2–3weeks. Then patients resumed full oralhygiene. At the end of the ‘‘early healingphase’’, patients were placed on a 3-month recall system for 1 year.

Data analysis

A total of 20 patients were enrolled inthis case series. Five out of 20 weretreated with the original MIST forreasons associated with the defect

accessibility. Data were expressed asmeans � SD of 15 defects in 15 patients(M-MIST) and five defects in fivepatients (MIST). No data points weremissing. Comparisons between baselineand 1 year CAL, PPD and REC weremade using the paired Student’s t-test(a5 0.05). Percentage fill of the base-line intrabony component of the defectwas calculated as: CAL% 5 (CALgains)/INFRA � 100.

CAL gains, residual PPD and positionof the gingival margin were the primaryoutcome variables.

Results

Experimental population andsurgical approach

Twenty intrabony defects in 20 subjects(mean age 48.1 � 10.4, range 31–65years, 12 females, and non smokers),who fulfilled the admission criteria,were included in this case cohort. TheM-MIST was applied in 15 of the20 selected sites (mean patient age46.1 � 10.3, range 31–65 years, ninefemales). The remaining five sites(mean patient age 54 � 9.0, range 44–64 years, three females) presenteddefects involving the lingual side andrequired the elevation of the interdentalpapilla and the lingual flap to ensureappropriate debridement and manage-ment of the defect. The decision wastaken during the surgery, after theremoval of the granulation tissue fromunder the papilla. These defects weretherefore treated with the MIST(Cortellini & Tonetti 2007a, b).

M-MIST-treated population

Patient and defect characteristicsat baseline

FMPSs and FMBSs at baseline were13.1 � 4.7% and 5.8 � 3.0%, respec-tively (Table 1). CAL of 9.7 � 1.8 andPPDs of 7.7 � 1.5 mm on average wererecorded (Table 1). The radiographicdefect angle was 32.1 �4.11. The distance from the cemento-enamel junction to the bottom of thedefect (CEJ-BD) was 11.1 � 2.3 mm,and the intrabony component of the de-fects (INFRA) was 6 � 1.5 mm (Table 1).

Design of the surgical flap and surgicalchair-time

The SPPF was used in five of the 15 M-MIST-treated sites and in all the cases



the buccal incision was restricted tothe defect-associated papilla. Verticalreleasing incisions were never per-formed. The average M-MIST surgicalchair-time was 56.5 � 8.6 min. (range43–69 min.).

Primary closure of the flap andpost-operative period

In all treated sites, primary closure wasattained at completion of the surgicalprocedure. All the treated sites remainedclosed during the 6 weeks of the earlyhealing period. No oedema or haemato-ma was noted in any of the treated sites.None of the patients reported any intra-operative pain and personal feeling ofhardship of the procedure at the end ofsurgery. At week 1, none of the patientsreported significant postoperative pain.Three patients reported very limiteddiscomfort in the first 2 days of the firstpost-operative week. Fourteen out of 15described the first postoperative week asuneventful, reporting that they had nofeeling of having been surgically treatedafter the second post-operative day.

1-year clinical outcomes (Table 2)

The 15 patients presented at the 1-yearfollow up visit with FMPS and FMBS of12.2 � 4.4% (range 5–20) and3.7 � 2% (range 0–7), respectively.The differences in FMPS and FMBS

between baseline and 1 year were notstatistically significant (p 5 0.099 and0.055, respectively).

The 1-year CAL was 5.1 � 1 mmwith a clinical attachment gain of4.5 � 1.4 mm (range 3–9 mm). Differ-ences in CAL between baseline and 1year were clinically and statisticallyhighly significant (po0.0001). The 1-yearCAL% was 75.5 � 10%, with a rangeof 62.5% to 100%.

Residual PPDs were 3.1 � 0.6 mm,with an average pocket depth reductionof 4.6 � 1.5 mm. Differences betweenbaseline and 1-year PPDs were clini-cally and statistically highly significant(po0.0001). Only three sites showed aresidual PPD of 4 mm; all the other sitesshowed a 1-year PPD of 3 mm or less.

A minimal average change of0.07 � 0.3 mm in the position of thegingival margin between baseline and1 year was observed. This difference didnot reach statistical significance(p 5 0.167).

MIST-treated population

Patient/defect data and 1-year outcomesthat refer to the five MIST-treated casesare reported in Table 3.

The SPPF was used in three out offive MIST-treated sites. The buccal inci-sion in three MIST cases involved anadditional interdental space. The aver-

age MIST surgical chair-time was64.8 � 4.6 min. (range 59–70 min.).

Primary closure was attained andmaintained for 6 weeks in all sites.None of the patients reported anyintra-operative pain or personal feelingof the hardship of the procedure. Atweek 1, no oedema or haematoma wasnoted. Four out of five described the firstpostoperative week as uneventful. Onlyone patient reported limited postopera-tive pain and discomfort that lasted3 days.

Discussion

This clinical study was designed toexplore the applicability, the clinicaloutcomes and the patient perception ofan M-MIST, an extension of the MIST,designed to further reduce surgical inva-siveness in the treatment of isolateddeep interdental intrabony defects.

The design of this surgical approachallows both access to root surface instru-mentation and minimization of flap ele-vation through the elevation of thebuccal flap alone. This further enhanceswound stability during early woundhealing and prevents the collapse ofthe papilla into the defect: at the endof the procedure, the buccal flap isrepositioned and sutured to the inter-dental supracrestal soft tissues, stillanchored with their fibres to the rootcement. The improved stability of thesoft tissues could play a positive role inincreasing the stability of the blood clot,a key factor in regenerative therapy(Hiatt et al. 1968, Wikesjo & Nilveus1990, Haney et al. 1993). In addition,the potential prevention of the interden-tal soft tissue collapse could preservemore space for the regeneration tooccur.

On the other hand, the preservation ofthe ‘‘soft tissue roof’’ leaves a verylimited buccal access to the intrabonydefect. The limited access requires theuse of an operating microscope or, atleast, of magnifying lenses with ade-quate illumination, and microsurgicalinstruments. The granulation tissue issharply dissected and carefully‘‘carved’’ away from the intrabonycomponent. When the defect is deb-rided, the buccal side of the lingualwall of the defect becomes visible: atthis time, the clinician has to carefullyinspect the lingual side of the defect-associated tooth to find the limits ofthe intrabony defect. If the intrabony

Table 2. Clinical outcomes at baseline and 1 year after treatment of M-MIST treated cases(N 5 15)

Variables Baseline 1 year Difference Significancen

PPD (mm) 7.7 � 1.5 3.07 � 0.6 4.6 � 1.5 po0.0001REC (mm) 2 � 1.3 2.07 � 1.3 0.07 � 0.3 p 5 0.167CAL (mm) 9.7 � 1.8 5.13 � 1 4.5 � 1.4 po0.0001

nPaired t-test.

CAL, clinical attachment level; M-MIST, modified minimally invasive surgical technique; PPD,

probing pocket depth.

Table 1. Baseline patient and defect characteristics of M-MIST treated cases (N 5 15)

Variables Mean � SD Minimum Maximum

FMPS (%) 13.1 � 4.7 4 20FMBS (%) 5.8 � 3 1 11PPD (mm) 7.7 � 1.5 6 12REC (mm) 2 � 1.3 1 6CAL (mm) 9.7 � 1.8 7 14CEJ-BD (mm) 11.1 � 2.3 8 16INFRA (mm) 6 � 1.5 4 9X-ray angle (deg.) 32.1 � 4.1 25 40

FMPS, full mouth plaque score; CAL, clinical attachment level; CEJ-BD, cemento-enamel junction

and the bottom of the defect; M-MIST, modified minimally invasive surgical technique; PPD,




defect involves the lingual aspect, thelingual root planing becomes a verydifficult exercise. In this instance, itis suggested to extend the incision tothe interdental and oral crevices inorder to elevate the papilla to allowa direct vision of the lingual side,performing the MIST (Cortellini &Tonetti 2007a, b).

The defect population selected forthis study included only defects with aprevalent interdental intrabony compo-nent. The M-MIST was applicable in 15of the 20 selected defects. In five sites,the conventional MIST had to beapplied. As discussed above, thesedefects showed a consistent intrabonycomponent extending to the lingual/palatal side, which was detected duringthe procedure.

The application of the M-MISTresulted in a significant amount ofCAL gain (4.5 � 1.4 mm in defectswith an intrabony component of6 � 1.5 mm) associated with a remark-able stability of the gingival margin anda very shallow residual PPD (Table 2).The percent fill of the baseline intrabonycomponent of the defects in terms ofCAL gain ranged from 62.5% to 100%(average 75.5 � 10%), in agreementwith the results reported by the bestevidence of more conventional andmore invasive regenerative approaches(Cortellini & Tonetti 2000, 2005, Rosenet al. 2000, Murphy & Gunsolley 2003).Both the remarkable percent defect reso-lution and the minimal interdental softtissue recession could support thehypothesis of a positive influence ofthe surgical design on the clinical out-comes, even though this case cohortdoes not allow any conclusion or com-parison with other techniques: largecomparative studies are needed to

explore the potential of the proposedtechnique in depth.

From a patient’s standpoint, this wasa very well tolerated and relativelyshort procedure (surgical chair-time56.5 � 8.6 min., range 43–69 min.).Patients reported an uneventful post-operative period with very limited/nopain and discomfort.

The five cases treated with the MISThad very similar clinical outcomes, alonger surgical chair-time and very lowpatient morbidity; however, no compar-ison between the two techniques can beperformed.

In summary, M-MIST associatedwith EMD resulted in improved clinicaloutcomes with no or minimal patientmorbidity. It was easily applicable toisolated interproximal intrabony defectswith a prevalent interdental componentwith no or minimal involvement of thelingual/palatal side. There exists, there-fore, the need to carry out a carefuldiagnostic exercise before surgery toselect the potential M-MIST candidates.In addition, the surgeon has to be awareof the possibility of extending the M-MIST incisions to a MIST approach toallow for better lingual visibility whenneeded. The very limited soft tissueelevation of the M-MIST requires theuse of an operating microscope or lupewith good illumination for a direct viewof the defect. In addition, it basicallyeliminates the use of a barrier mem-brane, but allows the use of any biolo-gical material, grafting material or theircombination. This approach is poten-tially applicable as a pure flap surgery.A controlled study is ongoing to confirmand extend the reported positive preli-minary outcomes and to investigate thepotential of the M-MIST alone com-pared with use with EMD and with a

combination of EMD and a graftingmaterial.

Acknowledgements

This study was partly supported by theAccademia Toscana di Ricerca Odontos-tomatologica, Firenze Italy and theEuropean Research Group on Periodonto-logy (ERGOPerio), Berne, Switzerland.

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Address:

Dr. Pierpaolo Cortellini

Via Carlo Botta 16

50136 Firenze

Italy

E-mail: [email protected]

Clinical Relevance

Scientific rationale for the study. Toimprove wound stability and reducepatient morbidity, minimally inva-sive surgical approaches are beingdeveloped for periodontal regenera-tive therapy.

Principal findings. M-MIST wasapplicable in most of the selectedsites and its use in combinationwith EMD resulted in remarkableclinical improvements and very lim-ited patient discomfort.Practical implications. Applicationof M-MIST in combination with

EMD in the treatment of isolateddeep intrabony defects has the poten-tial to allow clinically significantoutcomes and to increase patients’acceptance of a regenerative proce-dure.



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