Evaluation of the efficacy of a bioactive synthetic graft material in the treatment of intrabony periodontal defects.

BACKGROUND: Bioactive ceramic fillers are synthetic materials which have shown the potential to enhance bone formation. The purpose of this study was to evaluate the efficacy of a bioactive synthetic graft material in the treatment of intrabony periodontal defects.
MATERIALS AND METHODS: Fourteen intrabony defects in twelve systemically healthy subjects having moderate to severe chronic periodontitis were evaluated after bone grafting with bioactive ceramic filler for a period of 6 months. Clinical and radiographic evaluations were made at baseline, at 3 and 6 months following surgery.
RESULTS: Mean radiographic defect fill of 64.76% (2.49±0.5 mm) was observed in 6 months, which was statistically significant. A statistically significant relative attachment level gain of 2.71±1.13 mm and probing pocket depth reduction of 4.21±1.18 mm was recorded at the end of the study. A significant decrease in mobility and gingival index was observed.
CONCLUSIONS: Bioactive glass is an efficacious treatment option for the reconstruction of intrabony periodontal defects as it led to statistically significant improvements in the clinical and radiographic parameters.

INTRODUCTION

The ultimate goal of periodontal therapy is to prevent further attachment loss and predictably restore the periodontal supporting structures that were lost because of the disease or trauma in a way that the architecture and function of the lost structures can be re-established.[1]

Functional reconstruction requires periodontal regeneration, which aims at the restoration of lost periodontium or supporting tissues and includes formation of new alveolar bone, new cementum and new periodontal ligament.[2] Current literature suggests that only guided tissue regeneration and osseous grafting have resulted in successful periodontal regeneration.[3] The efforts to obtain optimal regeneration of the periodontium has created a renaissance of research in the utilization of autologous, allogenic, and alloplastic implants in the treatment of periodontal osseous defects.[4]

Among alloplastic graft materials, bioactive ceramics is a group of osteoconductive materials including Hydroxyapatite, Flouroapatite, Bioactive glass and Tricalcium phosphate. Discovery of bioceramics was made in 1969 by a ceramic engineer Lary.[5] Bioactive glass is a ceramic composed principally of SiO2. The original composition of bioactive glass approved by FDA, designated 45S5 was, 45 mol% of SiO2, 26.9 mol% CaO, 24.4 mol% Na2O, 2.5 mol% P2O5. This material can bond to bone through development of a surface layer of carbonated hydroxyapatite, in situ. The calcium phosphate layer thought to promote adsorption and concentration of osteoblast derived protein necessary for mineralization of extracellular matrix.[6]

In the present study, an effort has been made to evaluate the efficacy of bioactive synthetic graft, as a periodontal regenerative material in the treatment of periodontal endosseous defects.

MATERIALS AND METHODS

Material

Commercially available bioactive glass (Novabone Dental Putty) was used as the material for study. According to manufacturer's claims Novabone Dental Putty is a premixed composite of bioactive calcium-phospho-silicate particulate which is composed solely of elements that exist naturally in normal bone (Ca, P, Na, Si, O) and an absorbable binder which is a combination of polyethylene glycol and glycerin. The material requires no mixing or preparation prior to application. This non hardening putty is ready to use and is to be applied directly to the intended graft site.

Study method

Patient selection

The study was carried out in the Department of Periodontology and Oral Implantology, National Dental College and Hospital, Derabassi, Punjab (India). 12 systemically healthy subjects (8 males and 4 females) suffering from moderate to severe chronic periodontitis, aging between 30-65 years, having radiographic evidence of one or more vertical defects (two or three walled) and probing pocket depth of 6 mm or more at the experimental site were enrolled.

Patients who had any medical condition or were on therapeutic regimen that could decrease the probability of soft tissue or bone healing, pregnant or lactating women, teeth with furcation involvement, non vital or endodontically treated teeth, third molars, one walled defects, patients with parafunctional habits i.e., bruxism and who had periodontal surgery in last 6 months, allergic to tetracycline, chlorhexidine were excluded. The study was approved by the institutional ethical committee.

Clinical parameters

The graft material was assessed on the basis of evaluation of certain selected clinical parameters, soft and hard tissue measurements of the experimental defect. The clinical parameters i.e., Probing pocket depth, Relative attachment level, Gingival recession, Mobility, Plaque index, Gingival index and Radiographic parameters (depth of intrabony defect) were recorded by a single investigator just before surgery as baseline data, and then were re-evaluated at 3 and 6 months post surgery.

Probing pocket depth was measured as the distance from the gingival margin to the base of the pocket using University of North Carolina probe. Relative attachment level and gingival recession was measured with same periodontal probe from a reference notch on a vacuum formed acrylic stent. Vertical grooving in the stent made proper alignment of the probe possible and ensured reliability and reproducibility for future comparisons.

To facilitate serial radiographic comparisons, intraoral periapical radiographs with attached X- ray grid, standardized by means of paralleling technique were utilized. The grid was calibrated in millimeters, which could be counted to measure the osseous defect fill on the radiograph.

Study protocol

After completing oral prophylaxis, subjects were re-evaluated after 4 weeks. The subject showing acceptable oral hygiene was selected for the study and signed written consents were obtained from the patients.

Surgical protocol

Surgical procedure was performed under local anesthesia. It included intrasulcular incisions, full thickness flap elevation, meticulous debridement and root planing, endosseous defect filling with bioactive glass, flap repositioning. Pre-suturing was done prior to the placement of graft material to prevent the dislodgment of the graft material with suture needle. Care was taken to avoid the overfilling of the defect so as to ensure adequate closure of the flap. Suturing was done with interrupted 3-0 silk sutures. Periodontal dressing was placed [Figures 1–6]. Routine Postoperative instructions were given to all the subjects.

Figure 1

Crevicular incision at the surgical site

Figure 6

Periodontal dressing, placed on the sutured surgical site

Flap reflection at the surgical site

Osseous defect after debridement

Osseous defect filled with graft material

Sutured surgical site

Antibiotics Doxycycline hyclate (100 mg every 12 hours on the day of surgery and every 24 hours for subsequent 7 days) were prescribed and Chlorhexidine mouth rinse (0.12%) twice daily for 14 days. Subjects were recalled after 7 days for suture removal. Scaling and root planning, motivation and oral hygiene instructions were reinforced at 1, 3 and 6 months recall visits. Clinical and radiographic parameters were re-evaluated at 3 and 6 months post surgery.

Statistical analysis

The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, version 15.0 for Windows). All quantitative variables were estimated using measures of central location (mean) and measures of dispersion (standard deviation and standard error). For time related comparison Paired t-test was applied. All statistical tests were two-sided and performed at a significance level of α=0.05.

RESULTS

Twelve patients in age group 30-65 years (M:F of 8:4) had participated in this study. Fourteen intrabony defects were treated with Novabone Dental Putty. All the treated sites resulted in uneventful healing. No complications such as allergic reaction, abscesses, or infections were observed throughout the study period, in any of the patients.

Statistically significant mean radiographic osseous defect fill of 64.76% (2.49 mm) was observed from baseline to 6 months [Table 1, Figures 7–10]. About 85% of the intrabony defects studied, had a defect fill of equal to or more than 50%, whereas 15% of the defects had less than 50% defect fill at the end of 6 months [Table 2].

Table 1

Mean percentage change in radiographic osseous defect measurements at different periods of observation

Figure 7

Radiographic osseous defect at baseline

Figure 10

Mean changes of radiographic osseous defect measurements between different observation intervals

Table 2

Showing defects with 50% or greater defect fill

Radiographic osseous defect fill after 3 months

Radiographic osseous defect fill after 6 months

To analyze the association of radiographic osseous defect fill to initial radiographic osseous defect depth, the defects were categorized in to two groups for descriptive purposes: Group I: Defects with baseline radiographic depth less than or equal to 3 mm.(n=7), Group II; Defects with baseline radiographic depth of defect more than 3 mm.(n=7)

In group I radiographic osseous defect fill of 76.19% was observed from baseline to 6 months, which was statistically significant [Table 3]. In this group, all the defects had 50% or greater radiographic osseous defect fill after 6 months. Group II had a radiographic osseous defect fill of 53.3% over a period of 6 months [Table 3]. Intergroup comparisons revealed that the difference in radiographic osseous defect fill was statistically significant for group I as compared to group II.

Table 3

Summary of mean percentage radiographic osseous defect fill after 6 months in group I and group II

A statistically significant probing pocket depth reduction of 4.21±1.18 mm was recorded after 6 months, (P<0.001) [Table 4, Figure 11]. A mean relative attachment level gain of 2.71±1.13 mm was observed at the end of study period [Table 4, Figure 11], which was statistically significant. A statistically significant (P=0.003) decrease of 0.71±0.72 was observed in mean mobility score from baseline to 6 months [Table 5, Figure 12]. A decrease of score by 0.44±0.46 in gingival index over a period 6 months [Table 5, Figure 12] was observed which was statistically significant (P=0.003). An increase in gingival recession had also been observed.

Table 4

Summary of mean differences of probing pocket depth, relative attachment level and gingival recession at different periods of observation

Figure 11

Mean change in Probing pocket depth, Relative attachment level, Gingival recession between different periods of observation

Table 5

Summary of mean differences of mobility, plaque index, gingival index at different periods of observation

Figure 12

Mean change in mobility, plaque index, gingival index between different periods of observation

DISCUSSION

Successful periodontal regeneration relies on the reformation of an epithelial seal, deposition of new acellular extrinsic fiber cementum and insertion of functionally oriented connective tissue fibers in to the root surface and restoration of alveolar bone height.[1] Bone grafting is the most common form of regenerative therapy and is usually essential for restoring all types of periodontal supporting tissues.[5]

For some years, so called bioactive glass products have been available for the treatment of intrabony defects.[7] Bioactive glass has a good manageability, hemostatic and osteoconductive properties and it may also act as a barrier retarding epithelial down growth.[8-13] Wide spread use, popularity among the clinicians and manufacturer's claims made us interested to study this particular material. The present study has evaluated the efficacy of bioactive synthetic graft material (Novabone Dental Putty) in the treatment of intrabony periodontal osseous defects.

The amount of mean radiographic osseous defect fill was measured to be 64.76% (2.49 mm) after 6 months, which was statistically significant (P<0.001). These findings are in accordance with studies of Mengel, et al.,[14] Froum, et al.,[15] and Lovelace, et al.,[16] who showed a mean bone fill of 65.0%, 62.0% and 61.8% respectively in the bioactive glass treated sites. Park, et al.,[17] reported that a mean bone fill of 2.8 mm was observed in the intrabony defects which were treated with bioactive glass, which is favorably comparable to our study results of 2.49 mm.

Group I (Subjects with initial radiographic osseous defect measurement equal to 3 mm) had a mean percentage radiographic osseous defect fill of 76.19% and Group II (subjects having initial radiographic osseous defect measurement more than 3 mm) showed 53.33% osseous defect fill. These findings are strikingly different from as reported by Rummelhart JM, Mellonig, et al.,[18] who had stated that greater regeneration is anticipated in deeper defects. In our study, Group II had lesser osseous defect fill as compared to group I, despite of having greater initial radiographic osseous defect depth. This could possibly be attributed to a variety of factors which can affect the outcome of regenerative periodontal therapy like defect characteristics (no. of walls, circumference, depth of defect, width of defect), mobility, wound stability, plaque index, operator's technique and host factors etc. Amongst all the defects, about 85% had a fill of equal to or greater than 50%, whereas 15% of the defects had a defect fill of less than 50%.

It is difficult to compare measurements of osseous defect fill in the present study with previous studies because of mode of measurement. In majority of earlier studies, re-entry measurements were made whereas only radiographic interpretation was used in this study. The re-entry procedure was not performed because it causes a degree of ethical concern and is usually not accepted by the patient. Furthermore, during second surgery, the new connective tissue attachment may be disturbed and replaced by long junctional epithelium. Also the problem of loss of crestal alveolar bone following the second intervention remains unresolved.[5]

Comparing a graft material to open flap debridement for any study purpose does not seem to be ethical because we intentionally leave a site without grafting where it is indicated. Thus, clinician's goal to do the best possible for the patient cannot be accomplished. Secondly comparison of the two graft materials on contra-lateral sites seems to be controversial because it is not possible to find out exactly morphologically similar osseous defects on both the sides. Histology is the ultimate standard to assess periodontal regeneration but cannot be performed due the ethical concern as the tooth is needed to be sacrificed. Previous literature suggests that osseous defect fill is ranged between 10-30% for open flap debridement procedures,[19] whereas with the use of Novabone Dental Putty in the present study, 64.76% defect fill was recorded which was statistically significant.

A statistically significant mean probing pocket depth reduction of 4.21±1.18 mm was observed from baseline to 6 months. This reduction in probing pocket depth can be attributed to soft and hard tissue improvements following resolution of inflammation and to the osteogenic potential of the bone graft material used in the study. Our results are in agreement to the previous studies of Froum, et al.,[15] Lovelace, et al.,[16] Mengel, et al.[7] who had reported 4.26 mm, 3.07 mm, 3.8 mm reduction in probing pocket depth respectively over a period of 6 months in sites treated with bioactive glass. Other studies by Ong, et al.,[20] Park, et al.,[17] Zamet, et al.,[21] have also demonstrated statistically significant reductions in probing pocket depth over a period of 6 months in bioactive glass treated sites.

Relative attachment level gain of 2.71±1.139mm was statistically significant from baseline to 6 months. This gain in attachment level can be attributed to periodontal regeneration, long junctional epithelium formation and/or soft tissue healing at the base of the pocket. These findings are in accordance to the studies of Lovelace, et al.,[16] Froum, et al.,[15] who reported approximately similar mean attachment level gain of 2.27±0.8 mm and 2.96 mm respectively in the sites treated with bioactive glass. Mengel,[14] Park, et al.,[17] Singh, et al.,[5] also reported that the sites treated with bioactive glass have shown statistically significant gain of attachment levels 6 months post surgery.

A statistically significant decrease in mobility scores was recorded and the decrease patterns seemed to be a reflection of decrease of inflammatory state, formation of new fibrous attachment and alveolar bone in the grafted sites. This decrease may also be attributed to mechanical support provided by the graft material. These findings are in accordance to the studies of Froum, et al.,[15] Meffert, et al.,[22] who reported a decrease in mobility in the teeth which were treated with bioactive glass.

An increase in gingival recession may be attributed to the shrinkage of gingival tissues with the resolution of inflammation. These findings are in consistency with Froum, et al.,[15] Mengel, et al.,[8] Sculean, et al.,[14] who reported an increase of 1.29 mm, 1.20 mm, 1.28 mm in gingival recession respectively after 6 months of the implantation of graft material. Plaque index was monitored throughout the study period and a non significant change was observed. This variable is totally dependent on the patient's compliance and his/her efficacy to maintain oral hygiene. As the subjects were on continuous periodic recall, constant motivation, education and oral hygiene instructions revision have led to almost similar plaque scores at all the periods of observation, which have negated the possibility of the elucidation of effect of this variable on regeneration. Similarly non significant changes in plaque scores have also been reported in previous studies.[1423] A statistically significant improvement in gingival index may be attributed to the resolution of inflammation and return of the gingival tissues from a diseased state to health. These findings are in accordance to that of Park, et al.,[17] Sculean, et al.,[8] Demir, et al.[24]

The results of this study demonstrate that treatment of intrabony periodontal osseous defects with Novabone Dental Putty (A bioactive glass synthetic graft) has led to clinically and statistically significant probing depth reduction, relative attachment level gain and radiographic osseous defect fill. The improved clinical soft and hard tissue responses at the grafted sites may be a function of the chemical reactivity of the material. When the material comes in contact with body fluids a unique surface reaction occurs within minutes of implantation. Initially there is an ionic exchange whereby the cations are leached from the surface of the material in exchange for hydronium or hydrogen ions forming silanol groups (SiOH). This ion exchange process leads to an increase in interfacial pH.[25] Silanol groups bond to adjacent silanol group through a polycondensation reaction forming a silica rich gel layer on the particular surface. Silica plays a key role in developing the bone bonding of bioactive glass.[26] The silica rich gel layer has high surface area which creates a site for the redeposition of calcium and phosphorous from the graft material and the blood.[27] Within hours a calcium phosphorous layer forms on the top of the silica gel layer. Initially this calcium phosphorous layer is amorphous because it is thin, but with time as the layer builds up in thickness and size crystallinity is detected, it becomes a crystalline hydroxycarbonate apatite (HCA) layer which is identical to bone material. This apatite layer provides the basis for the bonding of bone and this material. This surface reaction occurs until all of the ions in the internal part of the glass have undergone ionic exchange and ultimately HCA layer becomes remodeled and incorporated into the bone. The primary advantage of bioactive glasses is their rapid rate of surface reaction which leads to the fast tissue bonding.[28] The silica rich layer has a negatively charged surface. This increases the electrostatic charges enough so that water is absorbed quickly. Hydrogen bonding occurs between water molecule and the hydroxyl groups of the silanol which gives bioactive glass cohesiveness.[29] The negative charged surface of HCA layer attract proteins such as growth factors and fibrin which act like an “organic glue” attracting osteoblastic stem cells to the layer which differentiate into osteoblasts and produce bone. Collagen attaches to the surface and embeds in to HCA layer. Apical migration of the junctional epithelium is indirectly inhibited by the extension of the collagen up to the junctional epithelium.[30] Bioactive glass can promote cementum repair.[31]

The results of this study demonstrate that treatment of intrabony periodontal osseous defects with Novabone Dental Putty has led to statistically significant probing depth reduction, relative attachment level gain and radiographic osseous defect fill.

CONCLUSION

Novabone Dental Putty resulted in statistically significant improvements in radiographic osseous defect measurements and clinical parameters. It was very well tolerated by the subjects. No adverse effects such as periodontal abscess, inflammation and/or allergic reaction in the treated surgical sites were reported. Although the clinical parameters i.e., probing pocket depth reduction, clinical attachment level gain and radiographic evidence of bone fill are proved to be consistent with the successful regenerative therapy, but these findings cannot be directly extrapolated as an outcome of periodontal regeneration, as these are not supported by histologic evidence. So future studies with more critically designed protocols, larger sample size and inclusion of histologic evidence as a criteria for periodontal regeneration, are warranted to further explore the potential of the Novabone Dental Putty as a periodontal regenerative material.