Article

Guided tissue regeneration for periodontal infra-bony defects

Eastman Dental Institute for Oral Health Care Sciences, Dept of Periodontology, University College London, University of London, 256 Gray's Inn Road, London, UK, WC1X 8LD.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 02/2006; DOI: 10.1002/14651858.CD001724.pub2
Source: PubMed

ABSTRACT Conventional treatment of destructive periodontal (gum) disease arrests the disease but does not usually regain the bone support or connective tissue lost in the disease process. Guided tissue regeneration (GTR) is a surgical procedure that specifically aims to regenerate the periodontal tissues when the disease is advanced and could overcome some of the limitations of conventional therapy.
To assess the efficacy of GTR in the treatment of periodontal infra-bony defects measured against conventional surgery (open flap debridement (OFD)) and factors affecting outcomes.
We conducted an electronic search of the Cochrane Oral Health Group Trials Register, MEDLINE and EMBASE up to April 2004. Handsearching included Journal of Periodontology, Journal of Clinical Periodontology, Journal of Periodontal Research and bibliographies of all relevant papers and review articles up to April 2004. In addition, we contacted experts/groups/companies involved in surgical research to find other trials or unpublished material or to clarify ambiguous or missing data and posted requests for data on two periodontal electronic discussion groups.
Randomised, controlled trials (RCTs) of at least 12 months duration comparing guided tissue regeneration (with or without graft materials) with open flap debridement for the treatment of periodontal infra-bony defects. Furcation involvements and studies specifically treating aggressive periodontitis were excluded.
Screening of possible studies and data extraction was conducted independently. The methodological quality of studies was assessed in duplicate using individual components and agreement determined by Kappa scores. Methodological quality was used in sensitivity analyses to test the robustness of the conclusions. The Cochrane Oral Health Group statistical guidelines were followed and the results expressed as mean differences (MD and 95% CI) for continuous outcomes and risk ratios (RR and 95% CI) for dichotomous outcomes calculated using random-effects models. Any heterogeneity was investigated. The primary outcome measure was change in clinical attachment.
The search produced 626 titles, of these 596 were clearly not relevant to the review. The full text of 32 studies of possible relevance was obtained and 15 studies were excluded. Therefore 17 RCTs were included in this review, 16 studies testing GTR alone and two testing GTR+bone substitutes (one study had both test treatment arms).No tooth loss was reported in any study although these data are incomplete where patient follow up was not complete. For attachment level change, the mean difference between GTR and OFD was 1.22 mm (95% CI Random Effects: 0.80 to 1.64, chi squared for heterogeneity 69.1 (df = 15), P < 0.001, I(2) = 78%) and for GTR + bone substitutes was 1.25 mm (95% CI 0.89 to 1.61, chi squared for heterogeneity 0.01 (df = 1), P = 0.91). GTR showed a significant benefit when comparing the numbers of sites failing to gain 2 mm attachment with risk ratio 0.54 (95% CI Random Effects: 0.31 to 0.96, chi squared for heterogeneity 8.9 (df = 5), P = 0.11). The number needed to treat (NNT) for GTR to achieve one extra site gaining 2 mm or more attachment over open flap debridement was therefore 8 (95% CI 5 to 33), based on an incidence of 28% of sites in the control group failing to gain 2 mm or more of attachment. For baseline incidences in the range of the control groups of 3% and 55% the NNTs are 71 and 4. Probing depth reduction was greater for GTR than OFD: 1.21 mm (95% CI 0.53 to 1.88, chi squared for heterogeneity 62.9 (df = 10), P < 0.001, I(2) = 84%) or GTR + bone substitutes, weighted mean difference 1.24 mm (95% CI 0.89 to 1.59, chi squared for heterogeneity 0.03 (df = 1), P = 0.85). For gingival recession, a statistically significant difference between GTR and open flap debridement controls was evident (mean difference 0.26 mm (95% CI Random Effects: 0.08, 0.43, chi squared for heterogeneity 2.7 (df = 8), P = 0.95), with a greater change in recession from baseline for the control group. Regarding hard tissue probing at surgical re-entry, a statistically significant greater gain was found for GTR compared with open flap debridement. This amounted to a weighted mean difference of 1.39 mm (95% CI 1.08 to 1.71, chi squared for heterogeneity 0.85 (df = 2), P = 0.65). For GTR + bone substitutes the difference was greater, with mean difference 3.37 mm (95% CI 3.14 to 3.61). Adverse effects were generally minor although with an increased treatment time for GTR. Exposure of the barrier membrane was frequently reported with a lack of evidence of an effect on healing.
GTR has a greater effect on probing measures of periodontal treatment than open flap debridement, including improved attachment gain, reduced pocket depth, less increase in gingival recession and more gain in hard tissue probing at re-entry surgery. However there is marked variability between studies and the clinical relevance of these changes is unknown. As a result, it is difficult to draw general conclusions about the clinical benefit of GTR. Whilst there is evidence that GTR can demonstrate a significant improvement over conventional open flap surgery, the factors affecting outcomes are unclear from the literature and these might include study conduct issues such as bias. Therefore, patients and health professionals need to consider the predictability of the technique compared with other methods of treatment before making final decisions on use. Since trial reports were often incomplete, we recommend that future trials should follow the CONSORT statement both in their conduct and reporting. There is therefore little value in future research repeating simple, small efficacy studies. The priority should be to identify factors associated with improved outcomes as well as investigating outcomes relevant to patients. Types of research might include large observational studies to generate hypotheses for testing in clinical trials, qualitative studies on patient-centred outcomes and trials exploring innovative analytic methods such as multilevel modelling. Open flap surgery should remain the control comparison in these studies.

Download full-text

Full-text

Available from: Helen V Worthington, Jan 02, 2014
1 Follower
 · 
192 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The present study investigated the periodontal regenerative potential of gingival margin-derived stem/progenitor cells (G-MSCs) in conjunction with IL-1ra releasing hyaluronic acid synthetic extracellular matrix (HA-sECM). Periodontal defects were induced at four sites in eight miniature-pigs in the premolar/molar area (-4 weeks). Autologus G-MSCs were isolated from the free gingival margin and magnetically sorted using anti-STRO-1-antibodies. Colony-formation and multilineage differentiation potential were tested. The G-MSCs were expanded and incorporated into IL-1ra-loaded/unloaded HA-sECM. Within every miniature-pig, four periodontal defects were randomly treated with IL-1ra/G-MSCs/HA-sECM (test-group), G-MSCs/HA-sECM (positive-control), scaling and root planning (SRP; negative-control-1) or left untreated (no-treatment; negative-control-2). Differences in clinical attachment level (ΔCAL), probing depth (ΔPD), gingival recession (ΔGR), radiographic-defect-volume (ΔRDV) and changes in bleeding on probing (BOP) between baseline and 16-weeks-post-transplantation, as well as periodontal attachment level (PAL), junctional epithelium length (JE), connective tissue adhesion (CTA), cementum regeneration (CR) and bone regeneration (BR) at 16-weeks-post-transplantation were evaluated. Isolated G-MSCs showed stem/progenitor-cell characteristics. IL-1ra loaded and unloaded G-MSCs/HA-sECM showed higher ΔCAL, ΔPD, ΔGR, PAL, CR and BR as well as a lower JE compared to their negative controls and improved BOP. G-MSCs in conjunction with IL-1ra-loaded/unloaded HA-sECM show a significant periodontal regenerative potential. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal Of Clinical Periodontology 04/2015; 42(5). DOI:10.1111/jcpe.12401 · 3.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Autologous transplantation of periodontal fibroblasts may be a promising technique to induce tissue regeneration in the treatment of periodontal disease. Spheroid culture is a form of three dimensional cell culture that promotes cell matrix interaction and cellular differentiation without recourse to exogenous growth factors. The aim of this study was to develop 3D spheroidal cultures of periodontal fibroblasts in vitro and characterize them with respect to their potential use in periodontal tissue repair and regeneration. In this study commercial normal periodontal fibroblasts were grown in spheroidal form in vitro using the liquid overlay technique. The fibroblast spheroids were characterized by histology, DNA quantification, scanning electron microscopy and immunohistochemistry. Over 14 days, periodontal fibroblasts formed viable spheroids which incorporated an extracellular matrix rich in collagen type I and periostin. Production of cementum attachment protein which is a marker of dental hard tissue formation, was not detected. This study shows that periodontal fibroblast spheroids may have the potential to be used as an adjunct for periodontal regeneration.
    Chiang Mai Journal of Science 12/2013; 40(40):1020-1029. · 0.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Periodontitis is a chronic inflammatory disease affecting the soft and hard tissues supporting the teeth, which often leads to tooth loss. Its significant impact on the patient's general health and quality of life point to a need for more effective management of this condition. Existing treatments include scaling/root planning and surgical approaches but their overall effects are relatively modest and restricted in application. The goal of regenerative therapy of periodontal defects is to enhance endogenous progenitors and thus promote optimal wound healing. Considering that the host or tissue might be defective in the periodontitis context, it has been proposed that grafting exogenous stem cells would produce new tissues and create a suitable microenvironment for tissue regeneration. Thus, cell therapy of periodontium has been assessed in many animal models and promising results have been reported. However, the methodological diversity of these studies makes the conversion to clinical practice difficult. The aim of this review is to highlight the primary requirements to be satisfied before the leap to clinical trials can be made. We therefore review cell therapy applications for periodontal regeneration in animal models and the concerns to be addressed before undertaking human experiments.
    Frontiers in Physiology 11/2013; 4:325. DOI:10.3389/fphys.2013.00325 · 3.50 Impact Factor