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   Table of Contents    
ORIGINAL ARTICLE
Year : 2015  |  Volume : 19  |  Issue : 5  |  Page : 545-553  

The use of nanocrystalline and two other forms of calcium sulfate in the treatment of infrabony defects: A clinical and radiographic study


1 Department of Periodontology and Oral Implantology, DAV (C) Dental College and Hospital, Yamunanagar, Haryana, India
2 Department of Periodontology and Oral Implantology, H.S Judge Institute of Dental Sciences, Chandigarh, India

Date of Web Publication13-Oct-2015

Correspondence Address:
Deepika Bali
Department of Periodontology and Oral Implantology, DAV (C) Dental College and Hospital, Yamunanagar, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-124X.156875

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   Abstract 

Background: Calcium sulphate(CS) is one of the oldest alloplastic graft materials used because of its biocompatibility, handling characteristics, porosity, different rates of dissolution, chemico-physical resemblance to bone mineral, ability to induce release of growth factors and potentially unlimited supply at a modest cost. Aim of the study was to evaluate the efficacy of 3 forms of calcium sulphate i.e. Nanogen (nCS)(+), BoneGen(+) and Dentogen(+) in treatment of infrabony defects and to compare their efficacy as bone grafting substitutes. Materials and Methods: A prospective randomized, double blind controlled study was conducted on 45 sites from 16 subjects having Moderate to Advanced Periodontitis who were divided into 3 groups i.e. Group I (Nanogen), Group II (Dentogen) and Group III (BoneGen) clinical along with radiographic measurements were taken at baseline, 6 and 12 months postoperatively. Results: There was no significant inter-group difference in mean clinical attachment level (CAL) values at different time intervals whereas Intra-group changes in CAL at 6 and 12 months as compared to baseline were significant statistically. In Group I, changes in CAL between 6 and 12 months were found to be statistically significant in comparison with Group II and III. Conclusion: Both Nanogen and BoneGen TR can be considered valuable options in the treatment of infra-bony periodontal defects. The faster degradation of Dentogen may negatively affect its bone regeneration potential.

Keywords: Bone graft, calcium sulphate, nanocrystalline, periodontal disease


How to cite this article:
Pandit N, Sharma A, Jain A, Bali D, Malik R, Gugnani S. The use of nanocrystalline and two other forms of calcium sulfate in the treatment of infrabony defects: A clinical and radiographic study. J Indian Soc Periodontol 2015;19:545-53

How to cite this URL:
Pandit N, Sharma A, Jain A, Bali D, Malik R, Gugnani S. The use of nanocrystalline and two other forms of calcium sulfate in the treatment of infrabony defects: A clinical and radiographic study. J Indian Soc Periodontol [serial online] 2015 [cited 2019 Dec 13];19:545-53. Available from: http://www.jisponline.com/text.asp?2015/19/5/545/156875




   Introduction Top


The science of periodontology and its impact on periodontal practice is changing rapidly as new information about the causes; diagnosis and treatment of periodontal diseases have become available at an ever-increasing rate.[1]

There are many outcomes possible from the periodontal therapy depending upon the goals, the type of therapy, and the methods utilized to evaluate it. These can range from slowing/eliminating the destructive process, maintaining an area for a defect repair and/or regeneration.

The management of periodontitis has progressed from simple debridement to the use of bone grafts, guided tissue regeneration, growth factors and tissue engineering. Recent advances in the bone graft have mainly considered the properties of osteogenesis, osteoconduction and osteoinduction and have focused on elimination of disease transmission, mitogenic and chemotactic effects of bioactive agents on periodontal ligament and alveolar bone cells in order to create a conducive environment for bone regeneration. Space creation and barrier placement have been documented to be two main aspects of regeneration.

Calcium sulfate (CS) and calcium phosphate compounds are attractive alternatives to autografts because of their biocompatibility, handling characteristics, porosity, and different rates of dissolution, and chemical and physical resemblance to bone mineral, ability to induce release of growth factors and potentially unlimited supply at a modest cost in addition to inhibition of epithelial migration.[2]

Although CS is osteoconductive and not osteoinductive in itself, whereas in the presence of bone and/or periosteum it appears to become osteogenic.[3] When sufficient organic matrix and functioning osteoblasts are present, these ions can be effectively utilized in bone formation. CS also seems to facilitate the migration of gingival fibroblasts and cell attachment and spreading and the angiogenic and anti-inflammatory potential of CS.[4],[5] A possible reason for the anti-inflammatory properties of CS is that it dissolves rapidly and is washed away before infection can occur.[6] CS degrades quickly over a period of 4–6 weeks and hence has a limited success as a bone graft for large defects (like molar extraction sites or sinus augmentation site). To address this problem, controlled release calcium sulfate (dentogen) and later on Nanocrystalline version of CS was developed.

Recent developments in nanomaterials and nanotechnology have provided a promising insight into the commercial applications of nanomaterials in the management of periodontal diseases. There has been significant progress made in recent years with the development and introduction of various metallic and polymeric materials structured in nano-scales. Nano-materials are of significant interest from a fundamental point of view because the properties of a material change when the size of the particles that makeup the material become nanoscopic.[7] To exhibit characteristic properties such as larger surface area, well-defined structure, high reactivity and easy dispersibility; CS has reached another level, that is, at the nanolevel.

The present study was undertaken to evaluate the comparative potential of nano-crystalline CS, BoneGen and Dentogen both clinically and radiographically.


   Materials And Methods Top


The study protocol was evaluated by the board of studies and approved by Ethical Committee of Pt. B.D. Sharma University of Health Sciences, Rohtak; Haryana, India. All clinical procedures were performed in accordance with the Declaration Of Helsinki and the Good Clinical Practice Guidelines. Permission and consent was also sought from the patients participating in the study. Patients were divided in three groups, that is, Group I (Nanogen), Group II (Dentogen) and Group III (BoneGen TR).

Study design

This study was a randomized, double-blind, controlled clinical study. Subjects were chosen randomly using randomization table (simple randomization) with no discrimination on the basis of caste, sex religion or socio-economic status into three different groups. Randomization eliminates bias in treatment assignment, facilitates blinding or masking of the identity of treatments from investigators and participants.[8] Clinical attachment level was used as the primary outcome variable of the study with bone fill and defect resolution as secondary outcome variables.

Patients

A total of 45 sites from 16 subjects were selected for the study from those attending the outpatients Department of Periodontics at DAV (C) Dental College and Hospital, Yamuna Nagar. The period of study was between September 2010 and June 2012. All patients underwent a presurgical initial treatment consisting of oral hygiene instructions, scaling, root planing and occlusal therapy as needed. After 4 weeks, the revaluation was done to confirm that patients maintain an acceptable level of plaque control. During this presurgical phase, study models were constructed, and customized occlusal stent with a groove in occluso-apical direction was fabricated for each patient to serve as a fixed reference point (FRP) for measurements. A single masked examiner performed all measurements with a manual calibrated UNC-15 periodontal probe [Figure 1]. Gingival crevicular fluid samples were also collected from sites of attachment loss to assess interleukin 1 beta (IL-1 β) levels in all three groups. Samples were collected before and 1 week after scaling and root planing and at 6 and 12 months postoperatively following grafting procedure.
Figure 1: Preoperative assessment done using a customized acrylic stent and UNC-15 periodontal probe

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Inclusion criteria

Patients with

(1) Moderate to severe periodontitis (2) systemically healthy patients with age range of 20–64 years (3) patients with probing pocket depths of ≥5 mm (4) defect depth of >3 mm as evidenced radiographically.

Exclusion criteria

(1) Acute infectious lesions in areas intended for surgery (2) smoking >10 cigarettes/day (or equivalent amount of other tobacco products) (3) pregnant females (4) alcohol or drug abusers (5) history of previous regenerative surgery at the same site; (6) any condition associated with poor compliance or failure to maintain good oral hygiene (Full mouth plaque score >20% (6) furcation area (7) restorations or carious lesions on root surfaces associated with the intra-bony defect.

Regenerative materials used in the study

Calcium sulfate which resorbs completely in 4–6 weeks and is replaced by host bone. As it resorbs, a calcium phosphate lattice forms which serves as an excellent scaffold for new bone growth. It resorbs at a rate of approximately 1 mm/week.[9]

BoneGen TR is a composite of CS and poly L-lactic acid (PLLA). PLLA is a polymer with a long history of safe use in implantable medical devices. It is biocompatible, non-toxic and biodegradable. This nano-composite bone graft material, with a CS to PLLA ratio of 96:4 provides benefits of CS with a slower degradation profile to allow for complete bone filling in large defects. It takes about approximately 16 weeks for complete degradation.[9],[10]

Dentogen is an FDA approved medical grade CS hemihydrate for bone regeneration in dentistry. It is developed and sold by Orthogen LLC [Figure 2].
Figure 2: Graft materials A, B and C

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In dental defects, Dentogen is completely degraded in 4–5 weeks. It is indicated in root perforations, infra-osseous defects, open apices, apicoectomy, dehiscences and fenestrations, post-extraction and sinus lifts. Particle size of Dentogen is 4.4 μm.[11]

The pellets of BoneGen come with a diameter of 425–850 μm. It retains the desirable properties of CS and undergoes slower, controlled degradation as compared to pure CS [Figure 2].

Nanogen is CS with a unique nanocrystalline granular structure that allows for a controlled dissolution that leads to complete graft resorption [Figure 2]. The granules that form the material consist of smaller agglomerated particles that increase the surface area of the material. As the CS granules undergo controlled degradation, the formation of a calcium phosphate layer on their surface stimulates bone regeneration.[12] The nCS particles in Nanogen have particles having diameters from approximately 50–500 nm.[13]

Periodontal surgery and maintenance care program

The surgical area was anesthetized. After intra-sulcular incisions, full thickness flaps were raised on the buccal and lingual/palatal surfaces of the teeth. Granulation tissue adherent to the alveolar bone and any associated osseous defect was removed. After thorough defect debridement, the patient was randomly allocated to one of the three groups Nanogen/Dentogen/Bonegen/(Group I, Group II and Group III) [Figure 3],[Figure 4],[Figure 5],[Figure 6],[Figure 7],[Figure 8]. The flaps were readapted and sutured in such a way so as to completely cover the defect. Patients were advised to rinse with a 0.2% solution of chlorhexidine gluconate twice daily for 2 weeks after surgery.
Figure 3: Preoperative clinical photograph of the defect in Group I

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Figure 4: Clinical photograph of the defect in Group II

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Figure 5: Preoperative clinical photograph of the defect in Group III

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Figure 6: Nanogen placed in the defect for Group I

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Figure 7: Dentogen placed in the defect for Group II

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They were prescribed a non-steroidal anti-inflammatory agent, Ibuprofen 400 mg thrice a day for post-operative discomfort and an antimicrobial agent, Augmentin (amoxicillin + clavulanic acid) 500 mg thrice a day for 5 days postoperatively. The patients were refrained from brushing at the surgical site or manipulating it in any way for 10 days. They were advised to start with gentle wiping using an extra-soft toothbrush and revert to routine oral hygiene measures after 4 weeks at which the flaps regain their normal strength. From 6 weeks and up to 6 months after surgery, all patients were recalled at 2–4 week intervals for plaque scoring, oral hygiene instruction (when needed), and professional tooth cleaning. No subgingival instrumentation was done at the experimental sites until 6 months. Then patients were recalled at 1-year.

Assessments

Photographs were then taken at baseline; during surgery after complete debridement; placement of graft material and flap suturing; at 6 and 12 months after surgery [Figure 3],[Figure 4],[Figure 5],[Figure 6],[Figure 7],[Figure 8],[Figure 9],[Figure 10],[Figure 11]. Intra-oral radiographs were acquired using the parallel technique with dental film in a commercially available film holder at baseline, 6 months and 12 months [Figure 12],[Figure 13],[Figure 14],[Figure 15],[Figure 16],[Figure 17],[Figure 18].
Figure 8: BoneGen placed in the defect for Group III

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Figure 9: 12 month postoperative photograph in Group I

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Figure 10: 12 month postoperative photograph in Group II

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Figure 11: 12 month postoperative photograph in Group III

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Figure 12: Preoperative clinical radiograph of the defect in Group I

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Figure 13: Preoperative radiograph of the defect in Group II

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Figure 14: Preoperative radiograph of the defect in Group III

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Figure 15: 12 month postoperative radiograph in Group I

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Figure 16: 12 month postoperative radiograph in Group II

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Figure 17: 12 month postoperative radiograph in Group III

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Figure 18: Radiograph standardization

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One masked examiner made the clinical measurements at baseline, 6 months and 12 months, and another masked examiner did the radiographic measurements. The clinical measurements were done using a manual calibrated UNC-15 probe. Clinical parameters recorded were plaque index (Sillness and Loe 1964), Gingival index (Loe and Sillness 1963), pocket depth and clinical attachment level (CAL).

Linear measurements were recorded to the nearest millimeter. The following landmarks were taken into consideration for increasing the PD and CAL. Pocket depth and Clinical attachment level were measured with the help of pre-fabricated acrylic stent. Three measurements made were:

  • Fixed reference point to the base of pocket (BOP)
  • Fixed reference point to the gingival margin (GM)
  • Fixed reference point to the cementoenamel junction (CEJ).


Pocket depth and CAL were measured as follows:

  • Pocket depth = (FRP to BOP) − (FRP to GM)
  • Clinical attachment level = (FRP to BOP) − (FRP to CEJ).


Interleukin 1 beta levels were assessed by enzyme-linked immunosorbent assay in all three groups at the first appointment, 1 week after scaling and root planning and at 6 and 12 months postoperatively. All assay procedures were performed according to the manufacture's recommendations. The gingival crevicular fluid was removed from storage and placed in the kits 150 µl sample buffer (containing 1%bovine serum albumin × phosphate buffer saline) for extraction and vortexed for 1 min. The samples were incubated at + 4 degree centigrade for one night and vortexed 3 min at the room temperature the following day. After that the samples were centrifuged for 10 min at 3500 g and levels of IL-1 β were recorded.

Statistical analysis

A statistical software program (SPSS version 13.0) was used for data analysis. The statistical analysis was performed using Paired parametric "t" test, Tukey-HSD test, and nonparametric ANOVA test.


   Results Top


At baseline, there was no statistically significant difference in PI and GI scores at all the time intervals. The difference in these values in both the groups when compared from baseline to Phase I was significant with no difference at other time intervals.

There was no significant inter-group difference in mean probing pocket depth at baseline, 6 months, 12 months (P > 0.05). On intra-group comparison, the mean change in probing pocket depth when compared to baseline was statistically significant at 6 months and 12 months respectively (P < 0.001).

There was no significant inter-group difference in mean CAL values at baseline (P = 0.840), 6 months (P = 0.916) and 12 months (P = 0.347) whereas Intra-group changes in CAL at 6 and 12 months when compared to baseline were significant statistically. In Group I, change in CAL between 6 and 12 months was also found statistically significant whereas in Group II and Group III, it was nonsignificant [Table 1].
Table 1: Intragroup comparison of PPD and CAL in three groups at different follow-up intervals

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Mean change during 6–12 months was maximum in Group III, which showed an increased percentage in defect fill to the twice of 4.4 ± 24.77, whereas in Group I and II negative change in defect fill was observed. There was a significant difference in the defect depth reduction and bone fill at 6 months and 12 months interval when intragroup comparison were done for all groups. The difference was non-significant from 6 months to 12 months. Although on inter-group comparison, the difference was non-significant for all the three groups at different time intervals, and the values were slightly better for group III. Similar observations were made for defect resolution where better values were obtained for group II [Table 2] and [Table 3].
Table 2: Intragroup change in percentage defect fill at different follow-up intervals

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Table 3: Intragroup comparison of defect depth reduction and amount of defect resolution in three groups at different follow-up intervals

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There was no statistically significant inter-group difference in Interleukin 1 beta levels suggesting that GCF levels of IL-1 β are not dependent on attachment levels [Table 4].
Table 4: Comparison of percentage change of IL-1 β from BL at different time intervals among different groups

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   Discussion Top


The complete and predictable restoration of the periodontium following trauma or infection remains a critical objective in periodontics. Bone replacement grafts remain among the most widely used therapeutic strategies for the correction of periodontal osseous defects. Trombelli et al.[14] and Reynolds et al.[15] in their systematic reviews summarized that bone replacement grafts and bone substitutes were significantly more effective than open flap debridement in improving attachment levels and in reducing probing depth.

Among the regenerative materials used in the study, CS is one of the first bone substitutes used in orthopedics and dentistry because of its properties. CS hemihydrate enhances bone regeneration by releasing calcium ions, which combine with phosphate ions from the body fluid to form a calcium phosphate trellis, a bioactive and osteoconductive bone scaffold. It is extremely effective as a barrier membrane, as a drug delivery vehicle and is completely degradable.[15]

Clinical observation

Statistically significant improvement in intra-group plaque was observed between baseline to Phase I and consistent with the improvement in PI score; there was an observable reduction in GI score.

Although plaque control instructions were explained and reinforced in all patients, improvements observed may also be because of improvement in CAL and reduction in probing pocket depth. Slotte et al. in 2012 in their study excluded patients who had full mouth plaque score >20%.[16] Similar criteria was used in this study.

It has been shown by Rosenbulum et al. 1993[17] that fibroblast growth factor is released in an active form from a Plaster of Paris carrier and the release of the growth factor was directly proportional to the degradation rate of CS, which facilitates migration of gingival fibroblasts and cell attachment and spreading.[4]

Comparisons between different groups also showed no difference between the improvements in the pocket depth measurements at different time intervals. In Group II and III, maximum reduction in probing pocket depth was between baseline and 6 months itself whereas in Group I maximum reduction in probing pocket depth as compared to baseline was observed at 12 months [Table 1].

There was no significant inter-group difference in mean CAL values at different time intervals. Intra-group changes in CAL at 6 and 12 months as compared to baseline was statistically significant (P < 0.05) [Table 1]. In Group I, change in CAL between 6 and 12 months was also found statistically significant (P = 0.001) in comparison with Group II and III. These findings are in agreement with the results of Aichelmann-Reddy et al.[2] Couri et al.,[18] and Paolontonio et al.[19]

This signifies that there was the maximum stabilization of the graft results in term of connective tissue attachment in group II and III at 6 months intervals as compared to group I which showed maximum stabilization at 12 months period.

Reports have shown the presence of residual xenograft material at the site 8 years after grafting. CS resorbs completely in 4–6 weeks and is replaced by host bone. As it resorbs, a calcium phosphate lattice forms which serves as an excellent scaffold for new bone growth. It resorbs at a rate of approximately 1 mm/week.[9]

Other grafting materials may leave unresorbed encapsulated particles even at 12 month recall interval. Clinical significance of such a fate may be irrelevant. Probing depth reduction, CAL gain with a consequent resolution of inflammation and arrest of disease progression may be more important and desired outcome.

Even if there is a tendency for better results in the CS treated defects in terms of pocket depth reduction, these may not translate into greater CAL gains indicating a greater tendency toward gingival recession at the experimental defect sites.[20]

Peltier and Jones 1978 demonstrated that osteoconduction requires the bone-graft substitute to have a resorption rate similar to the rate of new-bone formation. If the rate of resorption is faster than the rate of bone growth, the new bone will not have a scaffold on which to travel. Conversely, if the graft material resorbs too slowly it may stay in the osseous defect and block the ingrowth of new bone.[21]

Defect fill and defect resolution are the main outcomes that are usually reported by regenerative studies by Grimard et al.[22] and Stavropoulos and Karring [23] While defect fill takes into account only the changes at the base of the defect; defect resolution takes into account the changes in alveolar crest that may occur with regenerative therapy in addition to fill of the defect at the base. Thus, it may be interpreted that defect resolution is a better parameter.

A study by Park et al. 2011 observed by surface microhardness testing that nCS was stronger than conventional CS, which provides an additional advantage to the scaffolding properties of the material.[13] Furthermore, the surface area of nCS was about 10 times greater than that of a conventional micron-sized form which allows for greater adsorption of growth factors, higher surface area for attachment of osseous cells and more efficient osteoconductivity. CS degradation and subsequent bone regeneration occur rapidly during a period of weeks or months.[13]

Nanocrystalline structure of CS granules allows the material to have a controlled degradation over 10–12 weeks (compared to traditional CS, which degrades in 4–6 weeks).[12] The combination between the controlled degradation of nCS and excellent properties of CS adequately supports graft resorption and bone remodeling whereas BoneGen TR has resorption rate of 16 weeks.[4] BoneGen is a composite of CS and PLLA. PLLA is a polymer with a long history of safe use in implantable medical devices. It is biocompatible, nontoxic and biodegradable. This nano-composite bone graft material, with a CS to PLLA ratio of 96:4 provides benefits of CS with a slower degradation profile to allow for complete bone filling in large defects. It takes about approximately 16 weeks for complete degradation.[9],[10]

Poly-L-lactic acid degrades at a rate sufficiently slow to be useful and undergoes hydrolytic de-esterification to form metabolites normally found in the body. Nevertheless, the lactic-acid-rich degradation products have the potential to significantly lower the local pH in a closed space surrounded by bone. It was hypothesized that this acidity may tend to cause abnormal bone resorption and/or demineralization.

There was statistically no significant inter-group difference in the mean amount of bone fill at follow up intervals.

No significant intra-group change in defect fill was observed between 6 and 12 months, that is, indicating that the defect had already been filled to an optimum level by 6 months. Mean change during 6–12 months was maximum in Group III whereas in Group I and II a negative change in % defect fill was observed [Table 2].

There were two cases in Group I where unexpected results were obtained. In one case, defect fill at 6 months was 44.4% and at 6 months it was found 11.1% and in other case, defect fill was 50% at 6 months and 37.5% at 12 months due to unexplained reasons.

Intragroup comparisons showed that there was a statistically significant improvement in the amount of defect resolution of all the groups from baseline to 6 months and 12 months.

The significant changes in defect resolution can be attributed to increase in the concentration of Ca 2+ ions as CS dissolves. The released Ca 2+ ions react with the PO4 ions in the body, re-precipitating as calcium phosphate, which stimulates osteoblastic activity.[12] CS resorption causes pH to drop thereby demineralizing the surface of nearby bone exposing and/or releasing bone morphogenetic proteins, transforming growth factor-beta and other growth factors contained in the bone matrix [11] [Table 3].

Engebretson et al. 2002 in their study observed that IL-1 β levels in GCF were not strictly a function of probing pocket depth and CAL and high GCF IL-1 β expression was in part a host trait.[24]

In our study, no statistically significant intergroup difference was found in all three groups, thus showing results in accordance with their outcomes [Table 4].


   Conclusion Top


Both Nanogen and BoneGen can be considered valuable options in the treatment of infrabony periodontal defects although the cost of these materials is not commensurate with the clinical outcome. The enhanced gain in CAL with Nanogen between 6 months and 12 months could be attributed to its controlled degradation over 10–12 weeks and release of fibroblast growth factor, which facilitates migration of gingival fibroblasts and cell attachment and spreading and also increased surface area due to its nano-size as compared to conventional micron-sized CS. Although our study did not show any advantage of NCS or CRP, radiographic and histological investigations have shown that the extraction socket grafted with NCS had fully regenerated with vital bone by 12 months.[12] However, to confirm the success of a Nanogen large study populations and longer evaluation time periods are required.

 
   References Top

1.
Pihlstrom BL. Periodontology for the general practitioner. Periodontol 2000 2001;25:7.  Back to cited text no. 1
    
2.
Aichelmann-Reidy ME, Heath CD, Reynolds MA. Clinical evaluation of calcium sulfate in combination with demineralized freeze-dried bone allograft for the treatment of human intraosseous defects. J Periodontol 2004;75:340-7.  Back to cited text no. 2
    
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Frame JW. Porous calcium sulphate dihydrate as a biodegradable implant in bone. J Dent 1975;3:177-87.  Back to cited text no. 3
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4.
Payne JM, Cobb CM, Rapley JW, Killoy WJ, Spencer P. Migration of human gingival fibroblasts over guided tissue regeneration barrier materials. J Periodontol 1996;67:236-44.  Back to cited text no. 4
    
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Strocchi R, Orsini G, Iezzi G, Scarano A, Rubini C, Pecora G, et al. Bone regeneration with calcium sulfate: Evidence for increased angiogenesis in rabbits. J Oral Implantol 2002;28:273-8.  Back to cited text no. 5
    
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Pecora G, Baek SH, Rethnam S, Kim S. Barrier membrane techniques in endodontic microsurgery. Dent Clin North Am 1997;41:585-602.  Back to cited text no. 6
    
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Kong LX, Peng Z, Li SD, Bartold PM. Nanotechnology and its role in the management of periodontal diseases. Periodontol 2000 2006;40:184-96.  Back to cited text no. 7
    
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Schulz KF, Grimes DA. Generation of allocation sequences in randomised trials: Chance, not choice. Lancet 2002;359:515-9.  Back to cited text no. 8
    
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Mamidwar S, Ricci JL, Harold A. Bone regeneration with calcium sulfate based bone grafts. Inside Dent 2006;2:1-7.  Back to cited text no. 9
    
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Mamidwar S, Weiner M, Alexander H, Ricci J.In vivo bone response to calcium sulfate/poly L-lactic acid composite. Implant Dent 2008;17:208-16.  Back to cited text no. 10
    
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Mazor Z, Mamidwar S, Ricci JL, Tovar NM. Bone repair in periodontal defect using a composite of allograft and calcium sulfate (DentoGen) and a calcium sulfate barrier. J Oral Implantol 2011;37:287-92.  Back to cited text no. 11
    
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Mazor TZ, Horowitz R, Ricci J, Alexander H, Matei IC, Mamidwar S. The use of a novel nano-crystalline calcium sulphate for bone regeneration in extraction socket. J Implant Adv Clin Dent 2011;3:10-20.  Back to cited text no. 12
    
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Park YB, Mohan K, Al-Sanousi A, Almaghrabi B, Genco RJ, Swihart MT, et al. Synthesis and characterization of nanocrystalline calcium sulfate for use in osseous regeneration. Biomed Mater 2011;6:055007.  Back to cited text no. 13
    
14.
Trombelli L, Heitz-Mayfield LJ, Needleman I, Moles D, Scabbia A. A systematic review of graft materials and biological agents for periodontal intraosseous defects. J Clin Periodontol 2002;29 Suppl 3:117-35.  Back to cited text no. 14
    
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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.  Back to cited text no. 15
    
16.
Slotte C, Asklöw B, Sultan J, Norderyd O. A randomized study of open-flap surgery of 32 intrabony defects with and without adjunct bovine bone mineral treatment. J Periodontol 2012;83:999-1007.  Back to cited text no. 16
    
17.
Rosenblum SF, Frenkel S, Ricci JR, Alexander H. Diffusion of fibroblast growth factor from a plaster of Paris carrier. J Appl Biomater 1993;4:67-72.  Back to cited text no. 17
    
18.
Couri CJ, Maze GI, Hinkson DW, Collins BH 3rd, Dawson DV. Medical grade calcium sulfate hemihydrate versus expanded polytetrafluoroethylene in the treatment of mandibular class II furcations. J Periodontol 2002;73:1352-9.  Back to cited text no. 18
    
19.
Paolantonio M, Perinetti G, Dolci M, Perfetti G, Tetè S, Sammartino G, et al. Surgical treatment of periodontal intrabony defects with calcium sulfate implant and barrier versus collagen barrier or open flap debridement alone: A 12-month randomized controlled clinical trial. J Periodontol 2008;79:1886-93.  Back to cited text no. 19
    
20.
Orsini M, Orsini G, Benlloch D, Aranda JJ, Sanz M. Long-term clinical results on the use of bone-replacement grafts in the treatment of intrabony periodontal defects. Comparison of the use of autogenous bone graft plus calcium sulfate to autogenous bone graft covered with a bioabsorbable membrane. J Periodontol 2008;79:1630-7.  Back to cited text no. 20
    
21.
Peltier LF, Jones RH. Treatment of unicameral bone cysts by curettage and packing with plaster-of-Paris pellets. J Bone Joint Surg Am 1978;60:820-2.  Back to cited text no. 21
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22.
Grimard BA, Hoidal MJ, Mills MP, Mellonig JT, Nummikoski PV, Mealey BL. Comparison of clinical, periapical radiograph, and cone-beam volume tomography measurement techniques for assessing bone level changes following regenerative periodontal therapy. J Periodontol 2009;80:48-55.  Back to cited text no. 22
    
23.
Stavropoulos A, Karring T. Guided tissue regeneration combined with a deproteinized bovine bone mineral (Bio-Oss) in the treatment of intrabony periodontal defects: 6-year results from a randomized-controlled clinical trial. J Clin Periodontol 2010;37:200-10.  Back to cited text no. 23
    
24.
Engebretson SP, Grbic JT, Singer R, Lamster IB. GCF IL-1beta profiles in periodontal disease. J Clin Periodontol 2002;29:48-53.  Back to cited text no. 24
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16], [Figure 17], [Figure 18]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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