Year : 2009 | Volume
: 20 | Issue : 4 | Page : 471--479
Calcium phosphate cement as a "barrier-graft" for the treatment of human periodontal intraosseous defects
JB Rajesh1, K Nandakumar2, HK Varma3, Manoj Komath3,
1 Dental Civil Surgeon, General Hospital, Alappuzha, Kerala, India
2 Former Professor and HOD, Department of Periodontics, Government Dental College, Trivandrum, India
3 Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Trivandrum, India
Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Trivandrum
Background : Calcium phosphate cements (CPC) are apparently good candidates for periodontal treatment by virtue of their biocompatibility, mouldability and osteoconductivity. However, the clinical efficacy in this regard has not been established. This study is aimed at the evaluation of the efficacy of a formulation of CPC in healing human periodontal intraosseous defects in comparison with hydroxyapatite ceramic granules.
Materials and Methods : In this clinical study, 60 patients with periodontal defects were divided into 2 test groups and 1 control group. The defect sites in the test groups were repaired with CPC and hydroxyapatite ceramic granules (HAG). Debridement alone was given in the control group. The progress was assessed at 3, 6, 9 and 12 months observation intervals through soft tissue parameters (probing depth, attachment level and gingival recession).
Results: CPC showed significantly better outcome. Probing depth reduction values of CPC, HAG and Control at 6 months were 5.40 ± 1.43, 3.75 ± 1.71 and 2.90 ± 1.48, and those at 12 months were 6.20 ± 1.80, 4.5 ± 1.91 and 2.95 ± 1.73. Clinical attachment gain values of CPC, HAG and Control at 6 months were 5.15 ± 1.50, 3.45 ± 1.96 and 2.25 ± 1.52, and those at 12 months were 5.80 ± 2.02, 3.55 ± 2.06 and 2.30 ± 1.78, In both cases the P value was < 0.001 showing high significance. The gingival recession over 12 months, for the CPC group is lesser than that in the HAG group and the value for the control group is marginally higher than both. Soft-tissue measurements were appended by postoperative radiographs and surgical re-entry in selected cases.
Conclusions: Calcium phosphate cement is found to be significantly better than hydroxyapatite ceramic granules. The material could be considered as a «DQ»barrier-graft«DQ».
|How to cite this article:|
Rajesh J B, Nandakumar K, Varma H K, Komath M. Calcium phosphate cement as a "barrier-graft" for the treatment of human periodontal intraosseous defects.Indian J Dent Res 2009;20:471-479
|How to cite this URL:|
Rajesh J B, Nandakumar K, Varma H K, Komath M. Calcium phosphate cement as a "barrier-graft" for the treatment of human periodontal intraosseous defects. Indian J Dent Res [serial online] 2009 [cited 2021 Jun 20 ];20:471-479
Available from: https://www.ijdr.in/text.asp?2009/20/4/471/59459
Osseous grafting and guided tissue regeneration are the currently recommended techniques for periodontal treatment, aimed to achieve better and predictable regeneration of the lost periodontium, than the conventional debridement.  In osseous grafting, tissue regenerating scaffolds, either natural bone (autografts, allografts and bone derivatives) or synthetic osteoconductive materials (alloplasts), are provided at the defect site. They integrate with the host bone and participate in the remodeling of the defect. , The technique of guided tissue regeneration (GTR) employs barrier materials to allow selective cellular repopulation on the root surface, to retard apical migration of epithelium and to exclude gingival connective tissue from the healing wound. ,
A host of materials has been introduced for periodontal treatment in the past 3 decades, ranging from biological to synthetic, ceramic to polymeric, inert to bioactive and permanent to resorbable. A vast literature could be found on these materials, studying various aspects and recording various levels of clinical success. ,,,,
Banked bone (allografts), which include iliac cancellous bone and marrow, normal freeze-dried bone and decalcified freeze-dried bone (DFDBA) is used widely in periodontal repair.  It has been demonstrated that derivatives of bone and teeth (growth factors and proteins, incorporated in suitable delivery systems) also could be used for the purpose. ,, The class of alloplasts consists of ceramics, glasses and composites, which are bioactive. Calcium phosphate ceramics such as hydroxyapatite (HA, the basic mineral of bone), tricalcium phosphate (β-TCP) and HA-TCP "biphasic" compositions are used for periodontal repair. Glassy compositions containing silica (bioglass and glass-ceramics) are popular by virtue of their faster resorption and higher bioactivity. Bioceramics and bioactive glass materials composited with polymers (eg, polymethyl methacrylate and hydroxyethyl methacrylate) are also used for this purpose.  Alloplasts, however, are less preferred because they lack cells and factors. ,,
Barrier materials used are either resorbable or nonresorbable. Nonresorbable barriers such as expanded poly-tetrafluoroethylene call for a removal surgery. To avoid this problem, resorbable membranes based on collagen, cellulose derivatives and biodegradable polymers are designed. , Calcium sulphate (better known as "plaster of Paris"), which acts rather as a filler than a membrane, has been used because it provides the GTR effect due to fast resorption. ,
A new class of alloplast materials, namely, calcium phosphate cements (CPC), raised certain hopes in periodontal repair in the early 1990s. These are aqueous based cements that get converted to hydroxyapatite upon setting. The combination of biocompatibility, osteoconductivity and resorbability makes it a unique material for grafting bony defects.  Different formulations odf calcium phosphate cements are designed and they have already demonstrated their usefulness in skeletal repair. ,
The early studies using CPC formulations in simulated periodontal bony defects in animal models (in monkeys by Hong et al.,  and in dogs by Fujikawa et al.,  ) provided clear evidences of regeneration of bone and the resorption of the material. However, despite these encouraging results, the first human trial of CPC for periodontal treatment by Brown et al.,  in 1998 was rather disappointing. This study compared a new CPC formulation with DFDBA in terms of the linear clinical parameters in 16 patients for 12 months. While DFDBA showed good outcome, CPC resulted poor healing, inferior to the debridement-alone cases. The bone fill was minimal and alveolar crestal resorption was significant. The results prevented the authors form recommending the use of CPC formulation for the treatment of vertical intrabony periodontal defects.  Though the reasons for the poor performance of CPC are not explicitly analyzed, the authors report exfoliation of the material through the gingival sulcus. Presumably, the CPC they used was prone to wash-out in blood/body fluids, which has been an ailing problem for the early CPC formulations.  Further explorations on the use of CPCs for periodontal repair were held up till the development of "washout-resistant" CPC formulations. ,,,, In 2002, Shirakata et al.,  experimented with such a CPC formulation, in the repair of surgically created periodontal defects in beagle dogs. Histology showed the formation of new cementum and periodontal ligament-like tissue. In a more recent work, Setoguchi et al.,  conducted a human clinical trial in which periodontal intra-bony defects were treated with a CPC product (Norian PDC). Evaluation during a 6-month interval demonstrated a significant improvement in clinical outcome in comparison with open-flap debridement. These results indicate that the new washout-resistant CPCs are promising materials for periodontal treatment.
In this background, a study is planned to investigate the efficacy of a specially designed CPC formulation in human periodontal treatment. The material used in the study is "Chitra Calcium Phosphate Cement" (Chitra-CPC),  developed at the Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Trivandrum. , The product has undergone detailed tests and analyses prescribed for a bone graft substitute, the details of which could be found elsewhere. ,, This self-setting formulation has good rheological properties and washout resistance in wet environment.  The cement putty, upon setting, forms a microporous mass (with closed porosity) of hydroxyapatite. A histological study of 52 weeks by implanting in rabbit femoral bone showed that the cement filling remains stable at the site, is resorbed as the new bone grows in and leads to a complete healing of the defect. 
The present study aimed to compare the efficacy of "Chitra-CPC" calcium phosphate cement formulation and hydroxyapatite ceramic granules in the treatment of human periodontal defects resulting from periodontitis. Debrided sites without implantation are used as controls. The patient population is 60, with 20 patients in each group. The progress is assessed by evaluating soft-tissue parameters (probing depth, attachment level and gingival recession) for a period of 12 months, at 3-month intervals. Radiography and re- entry surgery are used for appending the results. On the basis of outcomes, the possible mechanisms of action of the CPC material and its future scope are envisaged.
Materials and Methods
The validation for clinical use of both the test materials has been reviewed by the Institutional Ethics Committee of Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Trivandrum, India.
The calcium phosphate cement product "Chitra-CPC" has been provided in a two-component (powder-liquid) sterile packing. The cement was prepared by adding the liquid dropwise onto the powder taken on a sterile glass slab and blending with a spatula (press-and-fold technique). Wetting ratio of 0.5 ml/g yields a putty, which upon working for a few minutes, forms a uniform lump. This could be applied to the defect site within the prescribed setting time.
The material used for comparison is, porous hydroxyapatite ceramic granules ("Periobone-G" approved for marketing in India), which has proven efficacy as a graft for the management of periodontal defects.  Sterile material in the particle size range 150-350 ìm was used. The granules were mixed with saline in a glass dish before being introduced into the defect site.
The patient recruitment was done from the lot registered in the Department of Periodontics, Government Dental College, Trivandrum, India, for the treatment of periodontitis. The clinical trial plan, including the patient informed consent form, has been approved by the Human Ethics Committee, Medical College, Trivandrum, India. The study has been conducted during the period from June 2005 to July 2006.
Patients of both sexes in the age range 20-45 years (mean age 32.75, SD ± 5.52) having moderate to severe periodontitis with angular osseous defects (two-wall or three-wall defects identified through probing) were screened. Those with probing pocket depth greater than 5 mm (but without any gingival recession at the site) and radiographic evidence of bone loss were selected for the study. Cases with adjacent furcation defects were avoided as far as possible. In case of multiple defects, only one site per patient was used for the study. The exclusion criteria were the presence of any systemic illness, prior antibiotic therapy for any illness during the past 2 weeks and any known allergic reactions to drugs. Pregnant women, lactating mothers and those who have the habit of using tobacco products, were avoided.
The selected patients were given instructions on self-performed oral hygiene techniques. Each of them was subjected to full-mouth supra and sub-gingival scaling and root planing, with occlusal adjustments, if necessary. A check-up for oral hygiene was done after 2 weeks and only patients who maintain optimal oral hygiene were recruited for the study. Essential initial therapy was completed at least 1 month prior to the commencement of the study. Detailed medical and dental histories were obtained from each patient and complete clinical examination was performed while recruiting.
The study population of 60 patients was divided into 3 groups consisting of 20 each, using random number table method. There were two test groups ("CPC Group" with calcium phosphate cement and "HAG Group" with hydroxyapatite granules), along with a control group (with debridement only). Before starting the trial, the nature of the study was explained to the patients and informed consent was obtained.
Clinical evaluation plan
The evaluation was focused on the periodontal soft tissue changes - reduction in probing pocket depth, gingival recession and gain in clinical attachment. To facilitate the measurements, customized acrylic stents were made for each patient, after preparing a study cast of the maxillary and mandibular teeth. The stents were grooved in an occlusoapical direction with a tapering fissure bur to standardize the angle of insertion of the periodontal probe (conventional Williams). The base of the stent served as reference point. Measurements, reckoned to the nearest millimeter, were taken from the reference point to gingival margin, cemento-enamel junction and base of the pocket [Figure 1].
Intraoral periapical radiographs were taken at each review to evaluate the bone fill at the site qualitatively, to supplement the clinical findings. Surgical re-entry was performed in two selected cases in the CPC Group at the end of the study period, to check the status of the periodontium after taking the informed consent of the patient. The HAG Group was not considered for re-entry because the evidences of repair with hydroxyapatite ceramic granules are available in the literature. ,
All surgical procedures were carried out under aseptic conditions in the Post-Graduate Clinic of the Department of Periodontics, Government Dental College, Trivandrum, India. All measurements, surgery and evaluations were done by the first author, under the monitoring of the principal clinical investigator (the second author).
The surgical area was locally anaesthetized using 2% xylocaine with adrenaline (1:2,00,000). Flaps were designed as intrasulcular incisions around teeth with full-thickness reflection to expose and allow thorough debridement of the defects. Care was taken to retain the interdental papillary tissue to the maximum possible extent. The involved root surfaces were prepared with scalers and curettes, under continuous normal saline irrigation to remove the debris. This was followed by isolation and drying of the areas. Subsequently, the root surfaces were conditioned with topical application of tetracycline hydrochloride in distilled water (100 mg/ml) for 4 minutes using cotton pellets. The areas were irrigated and dried again.
In the CPC test group, the calcium phosphate cement prepared in putty form was placed in the osseous defects to the level of the respective crest [Figure 2]. Similar grafting was done in the HAG test group, by mixing the hydroxyapatite granules with saline [Figure 3]. In the control group, no implantation was done after the open flap debridement. On finishing the procedures, the flaps were replaced to their original level and sutured with silk (interrupted suturing). Sufficient care was taken to achieve good primary closure over the grafted sites. Noneugenol periodontal dressings were given for 1 week. The patients were instructed not to disturb the dressing and to report, in case of any dislodgement.
Antibiotics (doxycycline, 100 mg BID for the first day followed by 100 mg OD for 5 days), anti-inflammatory analgesic (ibuprofen 400 mg TID for 3 days) and 0.2% chlorhexidine mouthwash were prescribed postoperatively. Patients were asked to report immediately if any untoward reaction (such as tooth pain or tissue inflammation) developed, to record the details in the Adverse Event Reporting form.
The periodontal dressing and sutures were removed after one week. Oral hygiene instructions were reinforced and gentle supragingival cleaning was carried out. The patients were given review appointments at 3, 6, 9 and 12 months post-surgically, for the data collection. At each visit, plaque control and mechanical debridement were also carried out.
Data collection and analysis
Measurements recorded preoperatively (after the hygienic phase) and at the review visits (3, 6, 9 and 12 months postoperatively), were used to calculate the soft tissue parameters. Consistent values were ensured before recording the measurement. The pocket depth reduction was determined by subtracting the measurement obtained at each observation period from the preoperative values of probing depth. Gingival recession was found by taking the difference in the gingival margin levels from reference point at each time period. The clinical attachment level was determined as the depth to the base of the pocket from the cemento-enamel junction and the attachment gain was calculated by subtracting the value obtained at each time period from the preoperative values of attachment level.
The changes in clinical measurement values were calculated for each defect site at 3, 6, 9 and 12 months, for each parameter (probing depth, clinical attachment level and gingival recession) in all groups. As the clinical parameters were found to follow the distribution normally, the analysis of variance was followed to compare the mean changes at different periods.  Statistical Software Package for Social Sciences (SPSS Version 10) has been used for the purpose. The statistical significance (measured at the P value of 0.05) among the different parameters in the various groups has been assessed with Duncan's Multiple Range test. 
All patients recruited in the study were available throughout the follow-up and postoperative healing was uneventful in all the cases. There was no gingival inflammation or soft tissue reactions adjacent to the grafted materials, in any of the cases in this study. All parameters in the control and the test groups were evaluated during the 3, 6, 9 and 12 months postoperatively. All patients maintained satisfactory oral hygiene throughout the study period.
A comparison of the values of probing depth (PD), clinical attachment level (CAL) and gingival recession (GR) of the study groups during the study intervals are given in [Table 1],[Table 2],[Table 3], respectively, along with statistical analysis. Comparison of the mean PD reduction during 12 months interval, the advantage with CPC group is notable (6.20 mm). The HAG group comes next (4.05 mm) and that of the control group was the least (2.95 mm). The mean attachment level values also follow the same pattern, with the level gains of 5.80, 3.55 and 2.30 mm during 12 months for the CPC group, the HAG group and the Control group, respectively. Over the 12-month interval, the mean gingival recession for the CPC group is 0.4 mm and that for the HAG group is 0.5 mm, whereas the value for the control group is 0.65 mm.
The differences in the preoperative measurements among the three groups are not found to be statistically significant for any of the variables assessed (P > 0.05), ensuring that the final comparison between treatments are not influenced by initial defect characteristics.
In CPC group, the variation in PD and CAL through 12 months shows high statistical significance (P 0.05). The similar statistical outcomes are seen in the case of the HAG group also. In the control group, where only debridement was given, the variation in PD and CAL during 12 months are highly significant (P  The progressive bone fill observed in the radiographs in the CPC group indicates almost a complete resorption of the material during 12 months.
In the surgical re-entry of two cases in the CPC group at the end of 12 months, significant bone fill was observed at the site, which correlated with the clinical attachment level observed at 12 months. Pictures of one case (male patient aged 25 years) are shown in [Figure 6], with corresponding radiographs. The bone at the site is seen to be coronal to the level of the defect than it was in the preoperative stage. A close visual examination revealed that the bone is remodeled and new periodontal ligament attachment is present.
An overview of the results shows that both the test materials (calcium phosphate cement and hydroxyapatite ceramic granules) are significantly efficacious in healing the periodontal defects when compared with open flap debridement. The calcium phosphate cement formulation (Chitra-CPC) is more efficacious than the hydroxyapatite ceramic granules.
Clinical efficacy of the materials
Sufficiently long and consistent record is available for hydroxyapatite ceramic granules, for its efficacy in the healing of periodontal defects. ,, Most of the comparisons are done with demineralized freeze-dried bone allograft (DFDBA). Typical values of mean bone fill for porous hydroxyapatite graft in the infrabony defects after 6 months of placement of the graft reported by various authors are 2.1 mm (Bowen et al.,  ), 3.42 mm (Oreamuno et al.,  ) and 3.53 mm (Kenney et al.,  ). The values with hydroxyapatite ceramic granules in the present study commensurate with the earlier reported values.
The work of Setoguchi et al.,  in which a CPC product is compared with open-flap debridement in 20 patient population, reports the pocket depth reduction and the mean clinical attachment level gain at 6 months to be 3.30 ± 1.17 mm and 1.95 ± 1.70 mm, respectively.  In the present study, for the CPC group, the pocket depth reduction and the mean clinical attachment level gain at 6 months are 5.40 ± 1.43 mm and 5.15 ± 1.5 mm, respectively. The corresponding values at 12 months are 6.20 ± 1.8 mm and 5.80 ± 2.02 mm, respectively. The advantage with Chitra CPC is notable.
The handling properties of Chitra-CPC also make it a better choice. Upon mixing and working, the material forms a mouldable and cohesive putty, which facilitates accuracy of placement [Figure 2]. Prior to the setting this putty can be shaped according to requirement and condensed into the defect easily. The packing obtainable is better than that of allograft (DFDBA) or ceramic granules.
Though Chitra-CPC is designed to resist washout in aqueous surroundings, , the consistency becomes paste-like in bleeding sites, thereby enhancing the setting time. Therefore, achieving hemostasis before the repair is advisable.
Scope of calcium phosphate cements in periodontal treatment
This study provides a compelling evidence for reinstating the interest in CPC for periodontal therapy. Calcium phosphate cements have not been seriously discussed in the reviews of periodontal regeneration materials, ,, probably because of the limited availability of published studies. Among the various materials DFDBA is advocated strongly for periodontal repair because of the superior gains.  Alloplasts, in general, could not demonstrate the formation of new cementum and functionally oriented ligament, and therefore deemed to serve only as scaffolds for new bone growth.  Some of the recent evidences make the class of CPCs an exception to this opinion.
The study by Shirakata et al.,  reports histological results of periodontal repair using an injectable, fast setting CPC in beagle dogs. They observed the formation of new cementum and periodontal ligament-like tissue during the healing of periodontal tissues. In a recent study by Hayashi et al.,  a CPC formulation has been used to treat periodontal defects created in dogs through experimentally induced periodontitis. At 12 weeks postimplantation, bone and cementum formation were consistently observed at the sites. New cementum and periodontal ligament-like tissue were seen between the CPC mass and the root surface. Also, new connective tissue attachment and adhesion were significantly enhanced at the sites, compared to nonimplanted sites (P  However, its use is governed by the proximity of bone banks. In countries where bone banks do not operate, procuring DFDBA is a cumbersome task due to regulatory hurdles and cost of import. Alloplasts, though considered inferior in performance, have an edge over DFDBA owing to off-the-shelf availability, adequate supply and consistency in product quality. If the efficacy of CPCs is proved comparable to (or better than) that of DFDBA, they could be recommended for global use in periodontal therapy.
Calcium phosphate cements as a barrier-graft
Techniques of periodontal therapy had been taking two independent routes, one with barrier materials and the other with grafts. Combination technique has also been experimented using DFDBA and GTR membranes, with a view to have more predictable outcomes. This, however, did not gain popularity, probably because of the complexity involved in the procedure.  The basic theories of grafting and guided tissue regeneration imply that a material that combines the properties of an osteoconductive graft and a resorbable barrier, (i.e., a "barrier-graft") can significantly improve the outcomes. Such a material should possess certain level of osteoconductivity to promote the growth of new bone, should allow selective cell repopulation and should be resorbable during the healing period. The virtues of CPCs seem to fit to the barrier-graft concept.
A notable feature of CPC material is osteotransductivity (i.e., resorption of the cement graft in tune with new bone formation), which is absent in other alloplast materials.  Cementing materials such as calcium sulphate undergo passive resorption in body fluid and disappear before new bone forms at the defect site.  On the other hand, hydroxyapatite ceramic granules are stable in body fluid but are too slow in resorption because of the sintered polycrystalline structure.  The solidified mass of CPC consists of submicron sized intergrown particles of hydroxyapatite with weaker interparticle boundaries compared with sintered ceramics.  It is chemically stable in body fluid, yet osteoclast cells can act upon and resorb the hydroxyapatite particles easily. While the cell-mediated resorption progresses, the osteoblast cells proceed with laying new bone in the space between host bone and the material. The new bone formed eventually gets converted to lamellar bone. This process will continue till the whole material is resorbed and the defect is repaired completely. ,,
CPC material should be able to exhibit the barrier-graft action because of the cementing property and osteotransductivity. Being a mouldable cement, it conformally fills up the defect. The filling excludes connective tissue and functional epithelium from the healing defect, thereby satisfying the criterion for a GTR barrier. At the same time, being osteotransductive, it induces remodeling of the bony defect and resorbs in the course of time. It could be proposed that more predictable and better outcomes could be achieved in periodontal therapy with the use of CPC. More studies are needed to establish this hypothesis.
The authors thank the authorities of Sree Chitra Tirunal Institute for Medical Sciences and Technology and Government Dental College, Trivandrum, India, for providing necessary facilities to carry out the work.
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