|Year : 2016 | Volume
| Issue : 1 | Page : 50-56
Evaluation of effectiveness of hyaluronic acid in combination with bioresorbable membrane (poly lactic acid-poly glycolic acid) for the treatment of infrabony defects in humans: A clinical and radiographic study
Bhumika Sehdev1, Manohar Laxmanrao Bhongade2, Kiran Kumar Ganji3
1 Department of Periodontology, R R Dental College and Hospital, Umarda District, Udaipur, Rajasthan, India
2 Department of Periodontology and Implantology, Sharad Pawar Dental College, Wardha (Affiliated to Datta Meghe Institute of Medical Sciences, Nagpur), Maharashtra, India
3 Department of Preventive Dentistry, College of Dentistry, (Affiliated to Al Jouf University), Al Jouf, KSA
|Date of Submission||17-Nov-2014|
|Date of Acceptance||25-Sep-2015|
|Date of Web Publication||25-Feb-2016|
Department of Periodontics, R R Dental and Hospital College, Umarda District, Udaipur, Rajasthan
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: The combination of biomaterials, bone graft substitutes along with guided tissue regeneration (GTR) has been shown to be an effective modality of periodontal regenerative therapy for infrabony defects. Therefore, the present randomized controlled clinical study was undertaken to evaluate the effectiveness of hyaluronic acid (HA) in combination with bioresorbable membrane for the treatment of human infrabony defects. Materials and Methods: Twenty four infrabony defects in 20 systemically healthy patients were randomly assigned to test (HA in combination with bioresorbable membrane) and control (bioresorbable membrane alone) treatment groups. Probing pocket depth (PPD), relative attachment level, and relative gingival margin level were measured with a computerized Florida disc probe at baseline and at 6 months follow-up. Radiographic measurements were also evaluated at baseline and at 6 months of postsurgery. Results: At 6 months, the mean reduction in PPD in test group and control group was 4.52 mm and 2.97 mm, respectively. Significantly higher clinical attachment level with a gain of 2.20 mm was found in the test group as compared to control group. In addition, statistically significant greater reduction of radiographic defect depth was observed in the test group. Conclusion: Regenerative approach using hyaloss in combination with GTR for the treatment of human infrabony defects resulted in a significant added benefit in terms of CAL gains, PPD reductions and radiographic defect fill, as well as LBG, compared to the GTR alone.
Keywords: Guided tissue regeneration, hyaluronic acid, infrabony defects
|How to cite this article:|
Sehdev B, Bhongade ML, Ganji KK. Evaluation of effectiveness of hyaluronic acid in combination with bioresorbable membrane (poly lactic acid-poly glycolic acid) for the treatment of infrabony defects in humans: A clinical and radiographic study. J Indian Soc Periodontol 2016;20:50-6
|How to cite this URL:|
Sehdev B, Bhongade ML, Ganji KK. Evaluation of effectiveness of hyaluronic acid in combination with bioresorbable membrane (poly lactic acid-poly glycolic acid) for the treatment of infrabony defects in humans: A clinical and radiographic study. J Indian Soc Periodontol [serial online] 2016 [cited 2019 Jun 25];20:50-6. Available from: http://www.jisponline.com/text.asp?2016/20/1/50/170809
| Introduction|| |
Human case studies and studies using discriminating animal models have pointed to a considerable native biologic potential for regeneration of the periodontal attachment, that is, formation of new cementum, alveolar bone, and a functionally oriented periodontal ligament (PDL).,,, Critical clinical components for successful outcomes are: (1) Wound stability during the early healing sequence, (2) space provision to allow the migration and proliferation of cells from the PDL and alveolar bone along the periodontally exposed root and (3) conditions favoring primary intention healing, that is, the wound space remains protected from bacterial contamination and infection.
A large body of clinical studies has applied the principles of guided tissue regeneration (GTR) to resolve periodontal infrabony defects., Outcomes from such studies have been rather variable, suggesting that the understanding of the fundamental biology for periodontal regeneration is incomplete, or its clinical application is difficult to master or complicated by events compromising periodontal wound healing.
In the last few years, various biomaterials have been tested to achieve periodontal regeneration in different types of periodontal defects. Polypeptide growth factors (platelet-derived growth factor [PDGF]) are the most thoroughly studied growth factor in periodontics. The results of a pilot human clinical trial using recombinant human PDGF BB (rhPDGF-BB) has shown mitogenic and chemotactic potential for PDL cells and bone cells thereby promoting regeneration of bone, PDL, and cementum. Bone morphogenetic proteins (BMPs) are another family of substances indicated as potential candidates for periodontal regenerative therapy. Studies in animal models showed their potential for periodontal tissue regeneration., However, one of the main issues for these materials is their release kinetics and need for a suitable carrier to keep the BMPs and growth factors in situ and to ensure space maintenance.
Recently, research has focused on a new substance, hyaluronic acid (HA), which is widely applied in other medical specialties such as ophthalmic and orthopedic surgery., HA has a number of embryological and bone healing properties, including the facilitation of cell migration and differentiation during tissue formation and repair., HA shares bone induction characteristics with osteogenic substrates such as bone morphogenic proteins. Recent studies demonstrated that HA aids in the repair process of both soft and hard tissue., It has been recently reported that HA increases osteoblastic bone formation in vitro through increased mesenchymal cells differentiation and migration. Pirnazar et al. demonstrated that HA may prove beneficial in minimizing bacterial contamination of surgical wounds when used in GTR surgery. However, few studies have examined its possible regenerative effects in dentistry, particularly in Periodontics., Therefore, the aim of the present randomized, controlled clinical study was to evaluate the effectiveness of HA in combination with bioresorbable membrane (poly lactic acid/poly glycolic acid [PLA/PGA]) for the treatment of infrabony defects in humans.
| Materials and Methods|| |
A total of 20 patients with moderate chronic periodontitis in the age range of 20–40 years (mean age 32.16 ± 8.12 years) were selected from the outpatient Department of Periodontics, Sharad Pawar Dental College (Sawangi), Wardha using following inclusion and exclusion criteria:
- Systemically healthy patients
- Presence of at least one radiographically detectable interproximal infrabony osseous defect with probing pocket depth (PPD) ≥5 mm and clinical attachment loss ≥5 mm following initial therapy
- Depth of intra-osseous component of the defect ≥3 mm by clinical and radiographic means and later confirmed intrasurgically
- A radiographic base of the defect at least 3 mm coronal to the apex of the test teeth
- The presence of at least 3 mm width of keratinized gingiva around test teeth.
- Patients with unacceptable oral hygiene (plaque index >1)
- Smokers or who used any of tobacco products
- Study tooth with inadequate endodontic/restorative treatments
- Clinical or radiographic signs of untreated acute infection, apical pathology, root fracture, severe root irregularities, cemental tears, cementoenamel projections not easily removed by odontoplasty, untreated carious lesions at cementoenamel junction (CEJ) or on the root surface at the selected site
- Study teeth showing mobility exceeding grade II, and class III/class IV furcation defect
- Pregnant females or lactating mothers
- Evidence of localized aggressive periodontitis.
The surgical procedures were explained to all the patients. Informed consent forms explained and signed prior to treatment. The protocol of the study was approved by the Ethical Committee of the Institution.
Each patient received initial therapy which included scaling and root planing, polishing, and oral hygiene instructions prior to surgical therapy. The occlusal adjustment was performed to eliminate centric prematurities and interferences and control mobility. Plaque control instructions were given until patients achieved a plaque score of ≤1.
Oral hygiene status
Patient's oral hygiene status was evaluated at baseline, 3 months and at 6 months by using full mouth plaque index (FMPI) and gingival health by full mouth papillary bleeding index (FMPBI).
The following clinical parameters were measured for assessment of the results in all the treated cases: PPD, relative-clinical attachment level (R-CAL), and relative gingival marginal level (R-GML), by using computerized constant force probe (Florida disk probe, Florida probe corporation, Gainesville, FL, USA) with a constant probing force of 15 g (pressure - 154 N/cm 2), tip diameter of 0.04 mm, precision of 0.1 mm and a probe length of 20 mm. These measurements were recorded at 6 sites of the selected teeth: Mesiobuccal, mesiolingual, distobuccal, distolingual, midbuccal, and midlingual. Only one measurement per defect, the deepest site of the selected defect at the baseline was included in the result calculations. All the clinical measurements were recorded on the day of surgery and at 3 months as well as at 6 months of postsurgery.
An intraoral periapical was taken of each selected site and was inserted in the mount to obtain following radiographic measurements; CEJ to base of bone defect (BD), CEJ to root apex and radiographic defect depth (DD). Linear bone growth (LBG) and percentage of bone fill (%BF) was also determined.
Study design and randomization
A total of 24 interproximal defects in 20 patients were found suitable after initial therapy. Prior to surgery, selected defects were randomly assigned by a coin flip to test and control groups each consisting of 12 defects, according to randomized parallel design. The test group was treated by HA in combination with bioresorbable membrane (PLA-PGA), while the control group was treated by bioresorbable membrane (PLA-PGA) alone.
Prior to the surgical procedure, the patients were instructed to rinse their mouth with 0.12% chlorhexidine gluconate solution (Hexidine, ICPA Health Products Ltd., India) for 1 min.
After infiltration with local anesthetic, intracrevicular (sulcular) incisions were given using Bard–Parker surgical blade #15 and 12 on the buccal and lingual aspects. Full thickness flap was reflected, and alveolar bone in the area of osseous defect was exposed. The osseous defect and inner surface of the flap was debrided of granulation tissue. The root surfaces were planned until a smooth hard consistency was obtained. At this stage, direct measurements of the vertical BDs, and the number of bony walls present were recorded. If BD was ≥3 mm vertically, final subject eligibility was confirmed. At this stage, the defects at test sites were treated with PLA-PGA membrane + HA.
Procedure for test group (hyaloss + bioresorbable membrane)
Complete isolation and hemostasis of the defect was achieved. A sterile aluminium foil was utilized to obtain the approximate dimension and shape of the membrane. The bioabsorbable membrane (BioMesh-S ®, Biodegradable GTR barrier, Samyang Crop., Korea) was trimmed in such a way that it completely covers the bony defect and extend at least 2 mm beyond the defect on all sides. Prior to the membrane placement over the defect, intramarrow penetration was performed with a half round bur. The flap was presutured without tying the knot to allow rapid flap closure after membrane placement.
The membrane was folded in half and then passed interproximally beneath the interdental contact and stabilized over the defect under the flap. Hyaloss matrix (HA – Esterified HA in the form of fibers, Hyaloss matrix ®, Meta, Italy) was mixed thoroughly with a few drops of physiological solution, in the sterile mixing container. The flap along with membrane was lightly raised on one side to fill the defect with hyaloss matrix. On contact with fluid, hyaloss matrix became gel and filled the BD, the excess gel was removed. The flap was coronally repositioned and sutured in such a way that the flap margin was located 1–2 mm coronal to CEJ, thereby completely covering the membrane. A combination of vertical mattress suture and interproximal sutures (4-0 nonresorbable surgical sutures, braided black silk, Mersilk, Ethicon, Johnson Ltd., India) was used to secure the flap in position. Slight pressure was applied to the area with saline-soaked gauze for approximately 2 min, to adapt the soft tissue well to the tooth surface and eliminate any space in which a clot might form and disrupt re-attachment. The surgical site was dressed with periodontal dressing (Coe-Pak ™, GC, Inc., Alsip, IL, USA) on buccal and lingual aspects.
Surgical procedure for the GTR group was identical to the GTR + HA group except the omission of placement of hyaloss matrix.
After surgery, a nonsteroidal anti-inflammatory, consisting of combination of ibuprofen 325 mg and paracetamol 400 mg, 3 times a day along with antibiotic consisting of amoxicillin 500 mg 3 times a day was prescribed for 5 days during postsurgical period. Patients were instructed not to brush the teeth in the treated area. All the patients were instructed to rinse with 0.12% chlorhexidine gluconate (Hexidine, ICPA) twice daily, for 1 min, for a week. They were instructed not to disturb the pack and to avoid undue trauma to the treated site.
One week following surgery, periodontal pack and sutures were removed. Patients were instructed to clean the treated site with cotton pellet saturated with 0.12% chlorhexidine gluconate for additional 2–3 weeks in an apico-coronal direction and later on using a soft toothbrush (Plakoff Plus ®, ICPA Health Products Ltd., India). The patients were recalled after 1 month, 3 months and 6 months following surgical treatment.
The means and standard deviation values were calculated for all clinical parameters including PPD, R-CAL, and R-GML. The mean data was analyzed for the statistical significance by the standard statistical method. Student's paired t-test was used to compare data from baseline to those at 3 months and at 6 months for each treatment group. Comparisons between treatment groups at baseline, 3 months and 6 months was accomplished with Student's unpaired t-test.
| Results|| |
During the course of the study, wound healing was uneventful. There was no untoward effects, allergy, infection or patient complaints related to the graft material. Hyaloss matrix fibers appeared to be clinically well tolerated by the periodontal tissues. None of the selected patients dropped out before the termination of the study.
[Table 1] shows FMPI and FMPBI scores at baseline, 3 months and 6 months follow-up in test group and control group. Mean PI and PBI scores remained nonsignificant at 6 months, indicating satisfactory improvement in gingival condition throughout the study period.
|Table 1: PI and PBI scores between baseline, 3 months and 6 months after surgery for 20 patients (mean±SD)|
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Clinical outcome at 6 months
Changes in probing pocket depth
At 6 months, the mean PPD reduction for control group (2.97 ± 0.85 mm) when compared with mean PPD reduction for test group (4.52 ± 0.48 mm), there was significantly greater mean PPD reduction of 1.55 ± 0.09 mm in test group compared with control group [Table 2].
|Table 2: Comparison of clinical and radiographic parameters between baseline and 6 months postsurgery for test group (hyaloss + GTR) (mean±SD)|
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Frequency distribution for PPD reduction at 6 months showed 2 sites (16.7%) in the control group, and 12 sites (100%) in the test group showed >3 mm of PPD reduction. While, 10 sites (83.3%) in the control group and 0 sites (0%) in the test group showed ≤3 mm of PPD reduction [Table 3].
|Table 3: Frequency distribution of clinical characteristics at 6 months for control and test groups|
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Changes in clinical attachment level
In control group, the mean R-CAL was decreased from 13.68 ± 0.79 mm at baseline to 11.40 ± 0.38 mm at 6 months with a mean CAL gain of 2.28 ± 0.41 mm. Student's paired t-test indicated that the mean CAL gain at 6 months was significantly greater (P < 0.05) when compared to the baseline data in control group (GTR).
In the test group, the mean R-CAL was decreased from 13.81 ± 0.87 mm to 9.33 ± 0.35 mm at 6 months with mean CAL gain of 4.48 ± 0.52 mm. Student's paired t-test indicated that the mean CAL gain at 6 months was statistically significant (P < 0.05) compared to the baseline data in the test group (hyaloss + GTR).
When comparison of CAL gain was made between the control group (GTR) and test group (hyaloss + GTR) at 6 months, there was significantly higher CAL gain of 2.20 ± 0.11 mm in test group (hyaloss + GTR) [Table 2].
The frequency distribution for >3 mm CAL gain at 6 months showed 1 site (8.3%) in control group (GTR) and 12 sites (100%) in test group (hyaloss + GTR) indicating greater percentage of CAL gain in test group (hyaloss + GTR) compared to control group (GTR). However, frequency distribution for ≤3 mm CAL gain at 6 months showed 11 sites (91.7%) in control group (GTR) and 0 sites (0%) in test group (hyaloss + GTR), indicating greater percentage of CAL gain of ≤3 mm in control group (GTR) compared to test group (hyaloss + GTR) [Table 3].
Changes in gingival recession
When comparison was made between control group (GTR) and test group (hyaloss + GTR) for mean gingival recession (GR) at 6 months, no statistically significant difference was found in increase in GR between the control and test group (P > 0.05) [Table 2].
The frequency distribution for >0.5 mm GR at 6 months showed 4 sites (33.33%) in control group (GTR) and 0 sites (0%) in test group (hyaloss + GTR) indicating greater percentage of GR in control group (GTR) compared to test group (hyaloss + GTR). However, frequency distribution for ≤0.5 mm GR at 6 months showed 8 sites (66.67%) in control group (GTR) and 12 sites (100%) in test group (hyaloss + GTR) indicating greater percentage of GR of ≤0.5 mm in test group (hyaloss + GTR) compared to control group (GTR).
Changes in radiographic analysis of defect depth
In the control group (GTR), the mean radiographic DD was reduced from 4.08 ± 0.90 mm to 2.00 ± 0.95 mm at 6 months, with mean reduction in radiographic DD of 2.08 ± 0.05 mm (55.55%). In the test group (hyaloss + GTR), the mean radiographic DD was reduced from 4.25 ± 0.75 mm to 0.33 ± 0.49 mm at 6 months with the mean reduction in radiographic DD of 3.92 ± 0.26 mm (94%). When comparison was made between the control and test groups, statistically significant greater reduction of radiographic DD was observed in test group (P < 0.05) [Table 2], with additional benefit of 1.84 mm radiographic DD reduction in test group (hyaloss + GTR).
Radiographic analyzes of %BF and LBG revealed an improvement in DD for both control and test group [Table 4]a and [Table 4]b. At 6 months, %BF was significantly greater in test group (94 ± 8.74%) as compared to control group (55.55 ± 13.18%). LBG was significantly improved by 1.00 ± 0.22 mm in test group (3.25 mm) compared to control group (2.25 mm) at 6 months [Table 4]b.
| Discussion|| |
20 systemically healthy patients with 24 periodontal infrabony defects affected by chronic periodontitis were selected for the study. 12 sites were treated by hyaloss in combination with bioresorbable GTR membrane (test group) and 12 sites were treated by bioresorbable GTR membrane alone (control group) procedures.
During 6 months observation period, the wound healing was uneventful. There was no sign of allergy, infection, exposure or any other complication in any patient after the use of bioresorbable membrane in combination with HA. No resorbable membrane showed evidence of necrosis. Therefore, findings of this clinical study confirmed earlier studies are demonstrating the safety of hyaloss in multiple animals and human studies.,, None of the selected patients were dropped out before the termination of the study. Each patient showed good oral hygiene level and a healthy gingival condition throughout the duration of the study, as reflected by the low FMPI and FMPBI score.
The findings of the present clinical study indicate that the use of HA + GTR as a regenerative material was found to be effective in improving the clinical parameters compared to GTR alone. Change in the CAL following regenerative therapy is the single most commonly used clinical outcome variable. At 6 months postsurgery, a statistically significant greater amount of mean CAL gain (2.20 mm) was observed in the HA with GTR group when compared to the GTR alone group. The results obtained in the present study were compared with other studies reported on the use of esterified HA. Ballini et al. reported the mean gain of 2.6 mm CAL following application of esterifi ed HA in combination with autologous bone in treatment of infrabony defects. However, Vanden Bogaerde  reported a mean CAL gain of 3.3 mm at 12 months follow-up. The greater mean CAL gain in their study could be explained by the differences in initial DD. The clinical studies have demonstrated that the CAL gain following regenerative periodontal therapy is strongly dependent on the initial DD that is, greater the initial depth, higher is the CAL gain. In the present study, significantly greater mean CAL gain of 2.20 mm observed in hyaloss + GTR treated group in comparison with GTR alone group, could be related to molecular characteristics of hyaloss, since hyaloss is known to stimulate cell migration, cell proliferation and also act as a carrier for other molecules, such as BMPs-2.,
From clinical standpoint, it was more significant to observe that 100% of treated sites with hyaloss in combination with GTR experienced the CAL gain of more than 3 mm, while only 8.3% of sites treated with GTR alone showed CAL gain of more than 3 mm.
Reduction of pocket depth to limit the risk of local reinfection is a primary goal of periodontal therapy. Shallow pockets have a strong, negative predictive value for future disease progression while deep pockets in treated areas are risk indicators for periodontal disease progression. In the present study, pocket depth reductions were significantly greater in both test and control groups. The mean PPD reduction obtained in sites treated with hyaloss combined with GTR was 4.52 mm and 2.97 mm in GTR treated sites. A statistically significant greater reduction of mean PPD (1.55 mm) was observed in hyaloss combined with GTR group compared to the GTR alone group. The mean PPD reduction observed in the present study by using hyaloss + GTR are comparable with other studies reported on the use of hyaloss in combination with bioresorbable membrane. Engström et al. reported mean PPD reduction of 4.1 mm when hyaloss was used in combination with bioabsorbable PLA barrier. However, Vanden Bogaerde  reported mean PPD reduction of 5.8 mm (range: 0–10 mm) at 12 months following an application of HA. Greater reduction of PPD reported by Vanden Bogaerde  could be related to the inclusion of the initial probing pocket of variable depth, which may possibly have influenced the treatment outcome.
In the present study, frequency analysis demonstrated that all 12 sites (100%) treated with hyaloss in combination with GTR showed the mean pocket depth reduction of >3 mm, whereas in control group 2 sites (16.7%) showed pocket depth reduction of >3 mm and 10 sites (83.3%) reduction of ≤3 mm.
Periodontal surgeries are frequently associated with GR, an adverse effect that concerns both patients and clinicians. Regenerative approaches, however, potentially could help to limit this unwanted side effect. In the present study, increase in GR was observed to a limited extent in test group (0.04 mm), whereas slightly greater amount of recession was observed in control group (0.37 mm) at the end of 6 months, however, the difference was not statistically significant (P > 0.05). The observed mean increase in GR in the present study was lesser to that of one reported in other hyaloss study. Vanden Bogaerde  reported mean GR of 2.00 mm in hyaloss treated interproximal defects.
During 6 months period, the infrabony lesions in this study, responded well to hyaloss combined with GTR treatment with regards to reduction in radiographic DD. It is the experience of the investigators that the most accurate means of determining osseous defect response (crestal changes as well as within the defect) is by direct visualization at re-entry surgery, but a major disadvantage of re-entry procedure is the need for a second surgical procedure to visualize the osseous defect. To overcome this difficulty, radiographic monitoring of alveolar bone changes has been utilized with various degrees of success. Radiographic bone measurement is a noninvasive, painless alternative to direct bone measurement. Therefore in the present study, radiographic monitoring of alveolar bone changes was carried out as end point variable.
In the present study, reduction in radiographic DD was obtained by subtracting postsurgical DD from initial DD. At 6 months, DD reduction was significant in both test and control group. The mean DD reduction at 6 months in test group was 3.92 mm with 94% defect fill and 2.08 mm in control group with 55.55% defect fill. The mean DD reduction was significantly greater by 1.84 mm in test group compared to control group. Findings in the present study are comparable with the previous report using different biomaterials for the treatment of infrabony defects. Nevins et al. evaluated effectiveness of rhPDGF-BB (0.3 mg/ml) mixed with a synthetic beta tricalcium phosphate (β-TCP) for the treatment of infrabony defect and reported 2.6 mm linear bone gain and 57% of BF at 6 months. McGuire et al. treated four cases each with one infrabony defects using 0.3 mg/ml rhPDGF-BB + β-TCP and reported 88% BF at 18 months follow-up.
The most reliable outcome variable for assessing periodontal regeneration is human histology. Due to ethical considerations and patient management limitations, no histological evidence was obtained to establish the proof of periodontal regeneration. The importance of wound stability for bone and periodontal regeneration has been reported. Based on the histological evidence from human material, it may be assumed that the clinical improvements following esterified HA treatment may represent at least to some extent, a real periodontal regeneration characterized by the increase of osteoblastic activity by stimulating differentiation and migration of mesenchymal cells. Moreover, the physiochemical properties of HA help keep the growth factors responsible for tissue repair in situ.
| Conclusion|| |
From the analysis of the results and within the limitations of the present study, it can be concluded that regenerative approach using hyaloss in combination with GTR for the treatment of human infrabony defects resulted in a significant added benefit in terms of CAL gains, PPD reductions and radiographic defect fill, as well as LBG, compared to the GTR alone.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]