Guided tissue regeneration is defined by the glossary of the American Academy of Periodontology: A surgical procedure with the goal of achieving new bone, cementum, and PDL attachment to a periodontally diseased tooth, using barrier devices or membranes to provide space maintenance, epithelial exclusion, and wound stabilization.
Guided tissue regeneration aims to compartmentalize or exclude cells from the healing wound to allow for regeneration rather than repair. This concept was first explored by Melcher in 1976 he pointed out that 4 different type of cells can repopulate the root surface after treatment and only the periodontal ligament cells have the ability to differentiate and regenerate the attachment apparatus. After that it was verified by experimental and histological studies.
Since then several attempts have been made to apply this concept clinically to fulfil one of the major goals of periodontal therapy: regeneration of the lost tissue. The need to exclude the epithelial and gingival connective tissue cells led to the development of barrier membranes.
Materials used in Guided tissue regeneration
Several barrier membrane materials are used for guided tissue regeneration in periodontics. However, the ideal membrane for periodontal guided tissue and bone regeneration should have the following properties: biocompatibility, space maintenance ability, cell conclusiveness, integrated by the host tissues, and clinical manageability.
Including collagen, gelatin, chitosan or silk and more. Most commonly used is the collagen membrane. Most of the commercially available collagen membranes are developed from type I collagen or a combination of type I and type II1. The source of collagen comes from tendon, dermis, skin or pericardium of bovine, porcine or human origin.
Advantages of collagen include: good tissue integration, fast vascularization, biodegradation without foreign-body reaction, chemotactic action for fibroblasts, hemostatic property, weak immunogenicity, osteoblastic adhesion and their proven biocompatibility and capability of promoting wound healing.
However, one of the major drawbacks is too rapid biodegradation and to reinforce the mechanical and biodegradable stability to comprise the biocompatibility, various chemical, physical, and biological cross-linking methods have been introduced to cross-link collagen via cross-linking, the tensile strength of collagen was enhanced and their degradation time may be prolonged However, the residual reagents or secondary products during collagen implant degradation may have toxic effects, and thus limit their applications
Polylactic Acid (PLA) and Polylactic acid/Polyglycolic Acid Copolymer (PLGA). Polylactic acid (PLA) is one of the most common and important polymers used in GTR and GBR procedures because of its suitable mechanical properties and biocompatibility. The use of these membranes may be subject to drawbacks such as inflammatory foreign-body reactions associated with their degradation products.
Disadvantages of resorbable polymers in general includes: Lack of space making ability compared to non-resorbable membranes and Unpredictable degradation profile.
To overcome the drawbacks of the pervious types of membranes the use of combination was introduce to get better mechanical properties and more control on bio degradability. These included: blends of natural or synthetic polymers or both, the use of bio ceramics with polymers.
The clinical outcome of guided tissue regeneration varies significantly depending on multiple factors including: the size, shape and extent of the defect and the involved root location and morphology.
In a systematic review in 2002 by Jepsen et al.. they compared efficacy of guided tissue regeneration versus surgical debridement in the treatment of furcation defects. the review included 14 studies and concluded that Overall, GTR was consistently more effective than OFD in reducing open horizontal furcation depths, horizontal and vertical attachment levels and pocket depths for mandibular or maxillary class II furcation defects. However, these improvements were modest, variable and there was only a limited number of studies available to appraise the effects, thus limiting general conclusions about the clinical benefit of GTR.
In anthor systematic review and meta-analysis in 2013 by Chen et al. this review was conducted to review clinical evidence on the efficacy of guide tissue regeneration (GTR) with/without osseous grafting (OG) in treating periodontal furcation Class II defects. they concluded that GTR technique seemed to be more effective than open flap debridement for resolving Class II periodontal furcation defects, and the GTR and OG technique showed even better clinical results. The outcomes were better for mandibular molars than for maxillary molars.
In a randomized clinical trial published in 2017 by Jenabian, et al. using guided tissue regeneration with platelet rich growth factors for the treatment for grade II furcation involvement. Both groups showed clinical improvement with a trend of better parameters in the GTR and platelet rich growth factor group however there was no significant difference. One drawback of this study is the small sample size of only 8 participants.
In a more recent retrospective study in 2019. The study evaluated the effect of guided tissue regeneration on the horizontal and vertical component of furcation defects. they included 98 treated defects treated with GTR using an allogeneic cancellous bone graft and covered by an absorbable membrane with at least 1-year follow-up. They found that 5- and 10-year survival rates of the treated teeth were 86.5% and 74.3%, respectively. The vertical component of the defect and the location of the furcation were significantly related to the post-surgical 1-year CAL gain, whereas membrane exposure significantly affected tooth survival. They concluded that GTR using allogeneic cancellous bone graft and absorbable collagen membrane to be a viable option for treating furcation-involved teeth if the defect morphology and the location of the defect are favorable.
To concluded based on the evidence although GTR results in significant clinical improvements beyond those achieved with open flap debridement alone in class II mandibular furcation, complete furcation closure is a rare event. GTR therapy offers limited clinical benefits in the treatment of class II maxillary furcation and no advantage in the management of class III furcation.
In the treatment of intrabony defects
In a systematic review about the efficacy of guided tissue regeneration in the treatment of intrabony defect by Needleman in 2002. They included 11 studies and concluded that overall guided tissue regeneration was more effective than open flap debridement in improving attachment levels. However, there was marked variability between studies and general conclusions about the clinical benefit of GTR are limited by this heterogeneity
In a Cochrane systematic review in 2005 by Needleman et al. they included 17 studies. Some of the conclusions A meta-analysis comparing GTR with OFD indicates overall an increase in clinical attachment gain of 1.22 mm (95%CI [0.80,1.64]) and a probing depth reduction of 1.21 mm (95%CI [0.53,1.88]) of GTR over OFD. However, the highly statistically significant heterogeneity between studies indicates that these summary values should not be used to indicate the magnitude of the greater probing changes.
In a systematic review by Yen et al in in 2014. They compared the treatment effects of guided tissue regeneration on infrabony lesions between animal and human studies. They included 22 studies. They found no significant difference in the bone fill ratio in guided tissue regeneration with bone graft in humans 52% and animals 57%. The was also no significant difference in the bone fill ratio in guided tissue regeneration alone in human 54% and animals 59%.
In a systematic review from the American Academy of Periodontology Regeneration Workshop in 2015 by Kao et al. they included Fifty-eight studies provided data on patient, tooth, and surgical-site considerations in the treatment of intrabony defects and Forty-five controlled studies provided outcome analysis on the use of biologics for the treatment of intrabony defects. they concluded that 1) Biologics (enamel matrix derivative and recombinant human platelet-derived growth factor-BB plus b-tricalcium phosphate) are generally comparable with demineralized freezedried bone allograft and GTR and superior to open flap debridement procedures in improving clinical parameters in the treatment of intrabony defects. 2) Histologic evidence of regeneration has been demonstrated with laser therapy; however, data are limited on clinical predictability and effectiveness. 3) Clinical outcomes appear most appreciably influenced by patient behaviors and surgical approach rather than by tooth and defect characteristics. 4) Long-term studies indicate that improvements in clinical parameters are maintainable up to 10 years, even in severely compromised teeth, consistent with a favorable/good long-term prognosis.
In a split mouth randomized clinical trail by Ravi et al in 2017. They compared the use of guided tissue regeneration with or without the addition of platelet rich growth factors. Both groups showed clinical improvement with a trend of better clinical and radiographic parameters in the guided tissue regeneration and platelet rich growth factor group however there was no significant difference.
Anthor study by Khan in 2018 evaluated the use of tetracycline and guided tissue regeneration in the treatment of intrabony effect. The study included 20 subjects. The difference in the osseous fill was not statistically significant.
In a case series in 2019. The clinical outcomes and prognostics factors of allografts with guided tissue regeneration in the treatment of intrabony defects was evaluated. They included 157 intabony defect and found that Baseline PD, smoking, and membrane exposure were significantly related to CAL gain, whereas baseline CAL, age, frequency in maintenance visits significantly affected tooth survival. And suggested that guided tissue regeneration is a good option for the treatment of intrabony defects because it can improve both tooth retention rate and overall clinical outcomes.
With dental implants
In a systematic review on the use guided tissue regeneration with immediate implant placement by AlKudmani et al in 2017. They included 8 studies and concluded the use of a barrier alone significantly decreased buccal plate resorption and the remaining defects around the implants, and the use of both bone graft and membrane aided in soft tissue preservation. The optimal type of bone graft material was a combination of cortical autogenous and synthetic particulate when compared to each separately, whereas no difference was found between demineralized allograft and hydroxyapatite in decreasing bone loss.
The use of guided tissue regeneration is well established in periodontology. Several biomaterials are used in the fabrication of different types barrier membrane. Each has their unique advantages and disadvantages with no ultimate ideal material for every clinical scenario. Therefore, the choice of the type of the barrier membrane should be based on individual assessment of each case’s needs and requirements.
In the treatment of furcation defect substantial evidence supports the us eof guided tissue regeneration the treatment of grade II furcation involvement in mandibular molars. However, fewer evidence is available reporting lower success and survival rates to support their use in grade III or maxillary molars. Other factors such as the vertical element of the furcation involvement, tooth/root morphology should also be taken into considerations.
For the treatment of intrabody defects evidence suggest better clinical and radiographic results when using guided tissue regeneration versus open surgical debetriment. However other factors can influence the outcome of guided tissue regeneration such as the extent and morphology of defect.
Other applications with less evidence are in cases of ridge preservation, with implant placement and in case of aggressive periodontitis or perio-endo lesions.