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Periodontal disease is a bacterial infection-associated disease of the periodontal tissues characterized by the destruction of tooth-supporting structures, including alveolar bone. The ideal goal of periodontal therapy is the complete regeneration of alveolar bone in a healthy microenvironment free of infection. In this study, we found that berberine, a benzylisoquinoline plant alkaloid from Coptidis Rhizoma, strongly inhibited the growth of Porphyromonas gingivalis. Gingipain is the most important virulence factor of Porphyromonas gingivalis in the process of periodontal tissue destruction. Berberine also had an inhibitory effect on gingipain activity in a concentration dependent manner. Remarkably, berberine restored the downregulation of osteogenesis-related genes expression in bone mesenchymal stem cells (BMSCs) induced by Porphyromonas gingivalis infection, and significantly increased the expression of osteogenesis-related genes such as OSX, COLI, ALP, OCN and OPN compared to the control group. This results suggested that berberine may directly promote osteogenesis. Further in-vitro studies demonstrated that berberine statistically significantly promoted the osteogenic differentiation of BMSCs at concentrations of 1-10 μM. In the research on the mechanisms, we found that both total β-catenin and nuclear β-catenin accumulation were statistically significantly increased by berberine. And the transcriptional activity of β-catenin/TCF was about 2 folds higher than the control group. Furthermore, Wnt signalling specific inhibitor DKK-1 blocked the above effects of berberine. These demonstrated that Wnt/β-catenin signalling pathway was involved in the osteogenic differentiation induced by berberine. The antibacterial actions in combination with the promotion role in osteogenic differentiation position berberine as a prospective drug for periodontal tissue regeneration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective To report a case of successful allogeneic grafting of mesenchymal dental pulp stem cells (DPSCs) as preliminary findings in a patient with periodontal disease enrolled into clinical trial ISRCTN12831118. Methods Mesenchymal stem cells from the dental pulp of a deciduous tooth from a 7-year-old donor were separated from the pulp chamber and processed via enzymatic digestion and centrifugation. DPSCs were passaged and cultured on a 35 × 13 mm culture dish in minimum essential medium-alpha, without supplementation. After reaching 80% confluency, 5 x 10 6 allogeneic DPSCs in 250 µl phosphate buffered saline were seeded onto a dry scaffold of lyophilized collagen-polyvinylpyrrolidone sponge placed in the left lower premolar area of a 61-year-old patient with periodontal disease. Surgical access to the lower premolar area was achieved using the flap technique. Results At 3 and 6 months following allogeneic graft, the patient showed no sign of rejection and exhibited decreases in tooth mobility, periodontal pocket depth and bone defect area. Bone mineral density had increased at the graft site. Conclusions Regenerative periodontal therapy using DPSCs of allogeneic origin may be a promising treatment for periodontal disease-induced bone defects.

Objectives: The aim of this systematic review was to assess the study design and reporting of studies on periodontal regeneration, with respect to the effect of the provision of non-surgical periodontal therapy (NSPT) before surgery., Materials and Methods: A systematic search of the literature was conducted for studies on periodontal regeneration on Medline and EMBASE, complemented by a manual search. Initially, 3310 potentially eligible articles were identified., Results: A total of 293 studies were included in the review. Nearly 10% of studies did not include NSPT in the study protocol before regenerative surgery, while 14% of papers did not report this aspect. Seventy-six percent of studies reported that non-surgical subgingival debridement was performed before periodontal surgery (2 weeks to 6 months before surgery according to the different studies). However, no papers reported clinical and radiographic data before and after NSPT prior to periodontal surgery. Only 45% of papers reported timing of reassessment following NSPT, prior to proceeding with regenerative surgery., Conclusions: This review highlights the lack of reporting information on non-surgical periodontal therapy prior to periodontal regenerative surgery, calling for a revision of the current clinical protocols and of the study designs of periodontal regenerative surgery studies., Clinical Relevance: Periodontal regenerative surgery protocols should take into account the possible effects of non-surgical periodontal therapy in the clinical and radiographic healing of intrabony defects.

Destruction of the periodontium is normally associated with periodontal disease, although many other factors, such as trauma, aging, infections, orthodontic tooth movement and systemic and genetic diseases, can contribute to this process. Strategies (such as guided tissue regeneration) have been developed to guide and control regeneration using bioresorbable membranes and bone grafts. Although effective to a certain point, these strategies have the problem that they are not predictable and do not completely restore the architecture of the original periodontium. To achieve complete repair and regeneration it is necessary to recapitulate the developmental process with complete formation of cementum, bone and periodontal ligament fibers. Detailed knowledge of the biology of cementum is key for understanding how the periodontium functions, identifying pathological issues and for developing successful therapies for repair and regeneration of damaged periodontal tissue. It is the purpose of this review to focus on the role of cementum and its specific components in the formation, repair and regeneration of the periodontium. As cementum is a matrix rich in growth factors that could influence the activities of various periodontal cell types, this review will examine the characteristics of cementum, its composition and the role of cementum components, especially the cementum protein-1, during the process of cementogenesis, and their potential usefulness for regeneration of the periodontal structures in a predictable therapeutic manner., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The unique anatomy and composition of the periodontium make periodontal tissue healing and regeneration a complex process. Periodontal regeneration aims to recapitulate the crucial stages of wound healing associated with periodontal development in order to restore lost tissues to their original form and function and for regeneration to occur, healing events must progress in an ordered and programmed sequence both temporally and spatially, replicating key developmental events. A number of procedures have been employed to promote true and predictable regeneration of the periodontium. Principally, the approaches are based on the use of graft materials to compensate for the bone loss incurred as a result of periodontal disease, use of barrier membranes for guided tissue regeneration and use of bioactive molecules. More recently, the concept of tissue engineering has been integrated into research and applications of regenerative dentistry, including periodontics, to aim to manage damaged and lost oral tissues, through reconstruction and regeneration of the periodontium and alleviate the shortcomings of more conventional therapeutic options. The essential components for generating effective cellular based therapeutic strategies include a population of multi-potential progenitor cells, presence of signalling molecules/inductive morphogenic signals and a conductive extracellular matrix scaffold or appropriate delivery system. Mesenchymal stem cells are considered suitable candidates for cell-based tissue engineering strategies owing to their extensive expansion rate and potential to differentiate into cells of multiple organs and systems. Mesenchymal stem cells derived from multiple tissue sources have been investigated in pre-clinical animal studies and clinical settings for the treatment and regeneration of the periodontium.

Regeneration of destroyed periodontal tissue is a complicated problem in periodontal therapy. Conventional strategies such as surgical techniques, occlusive barrier membranes, and bone grafts have disadvantages that limit their application. Tissue engineering is a novel approach to regenerate periodontal tissue overcoming limitations of current strategies. In recent studies, researchers reported the potential of adipose-derived stem cells (ADSCs) to use in periodontal tissue regeneration. Unfortunately, in vivo studies indicated that small amount of alveolar bone formed using ADSCs implantation in the periodontal defects, which would be overcome by inducing osteogenic differentiation of ADSCs using osteoinductive biomaterials combined with ADSCs. Beta-tricalcium phosphate (beta-TCP) is an osteoinductive material which reported to induce osteogenic differentiation of adipose-derived stem cells. Based on the performed studies, we hypothesize that ADSCs from Wistar rat are isolated, induced by appropriate signaling molecules, seeded by beta-TCP, and then the complex was implanted into the periodontal defects in the same Wistar rat to observe the regeneration of periodontal tissue in vivo. This study will explore the possibility and application of ADSCs/beta-TCP complex for reconstructing periodontal defects. We believe it is especially useful to future clinical study and application in this field., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Aim: The objective of this research was to elucidate early events in periodontal wound healing/regeneration using histological and immunohistochemical techniques., Methods: Routine critical-size, supraalveolar, periodontal defects including a space-providing titanium mesh device were created in 12 dogs. Six animals received additional autologous blood into the defect prior to wound closure. One animal from each group was killed for analysis at 2, 5, 9, 14 days, and at 4 and 8 weeks., Results: Both groups behaved similarly. Periodontal wound healing/regeneration progressed through three temporal phases. Early phase (2-5 days): heterogeneous clot consolidation and cell activation in the periodontal ligament (PDL) and trabecular bone was associated with PDL regeneration and formation of a pre-osteoblast population. Intermediate phase (9-14 days): cell proliferation (shown by PCNA immunostaining)/migration led to osteoid/bone, PDL and cementum formation. Late phase (4-8 weeks): primarily characterized by tissue remodelling/maturation. Fibrous connective tissue from the gingival mucosa entered the wound early, competing with regeneration. By day 14, the wound space was largely filled with regenerative and reparative tissues., Conclusion: Activation of cellular regenerative events in periodontal wound healing/regeneration is rapid; the general framework for tissue formation is broadly outlined within 14 days. Most bone formation apparently originates from endosteally derived pre-osteoblasts; the PDL possibly acting as a supplementary source, with a primary function likely being regulatory/homeostatic. Blood accumulation at the surgical site warrants exploration; supplementation may be beneficial., (© 2012 John Wiley & Sons A/S.)

Periodontal disease, a worldwide prevalent chronic disease in adults, is characterized by the destruction of the periodontal supporting tissue including the cementum, periodontal ligament and alveolar bone. The regeneration of damaged periodontal tissue is the main goal of periodontal treatment. Because conventional periodontal treatments remain insufficient to attain complete and reliable periodontal regeneration, periodontal tissue engineering has emerged as a prospective alternative method for improving the regenerative capacity of periodontal tissue. However, the potential of periodontal regeneration seems to be limited by the understanding of the cellular and molecular events in the formation of periodontal tissue and by the insufficient collaboration of multi-disciplinary research that periodontal tissue engineering involves. In this paper, we first reviewed the recent advancements in stem cells, signaling factors, and scaffolds that relate to periodontal regeneration. Then we speculate that specific genes would improve regenerative capacity of these stem cells, which could differentiate into cementoblasts, osteoblasts and fibroblasts. In addition, the 3D scaffolds that mimic the different structure and physiologic functions of natural fibro-osseous tissue could be fabricated by rapid prototyping (RP) techniques. It was therefore hypothesized that gene-modified stem cells combined with rapid prototyping techniques would be a new strategy to promote more effective and efficient periodontal regeneration.

In an attempt to understand better the cells responsible for periodontal regeneration, cells from human gingiva, periodontal ligament and regenerating periodontal defects treated with expanded polytetrafluorethylene membranes were isolated, cultured and characterized. Guided tissue regeneration procedures were carried out on three human volunteers around molar teeth destined for extraction. After a 6-week 'healing phase', fibroblast cell cultures were established from explants of the regenerating soft connective tissue (RTF), as well as from the associated periodontal ligament (PLF) and gingiva (GF). Following stimulation with platelet-derived growth factor-beta (PDGF) and insulin-like growth factor-1 (IGF-1), [3H]thymidine-uptake and dye-binding assays were used to assess the rate of DNA synthesis and cell proliferation, respectively. Northern blotting was used to measure the expression of mRNA for the extracellular matrix proteoglycans decorin, biglycan and versican. The results show that the GF and RTF proliferated more quickly than the PLF. PDGF and IGF-1 were mitogenic for all three cell types. Decorin mRNA expression was stronger in the GF than the RTF and PLF, whereas versican mRNA expression was stronger in the GF and PLF than the RTF. Biglycan mRNA expression was strong in the PLF, moderate in the GF and weak in the RTF. The growth factors did not affect the mRNA expression for biglycan, but they upregulated versican and downregulated decorin mRNA. It can be concluded that RTF exhibits properties characteristic of a reparative phenotype. More specifically, it proliferates faster than PLF, from which it is derived, while exhibiting a unique pattern of proteoglycan mRNA expression. Therefore, this study demonstrates that fibroblasts obtained from the regenerating periodontal defects exhibit characteristics consistent with their ability to facilitate periodontal regeneration.

The aim of the present study was to investigate in monkeys the regrowth of oxytalan fibres in different types of acute and chronic periodontal defects following regenerative periodontal treatment. One-wall intrabony and mandibular furcation III-defects were produced surgically in 3 monkeys (Macaca fascicularis). After a 6-wk dental plaque accumulation period the defects were exposed using a full thickness flap procedure. The granulation tissue was removed and the root surfaces were scaled and planed. Additionally, fenestration-type defects were produced at the vestibular surfaces of the maxillary and mandibular canines by surgically removing the vestibular bone plates and the root cementum. Subsequently, the defects were treated with guided tissue regeneration (GTR), enamel matrix proteins (EMP), combination of EMP and GTR or with coronally repositioned flaps. The postoperative care included tooth cleaning once a week during the experiment. After 5 months the animals were sacrificed and and the block sections were embedded in paraffin. Eight microns histological sections were cut and stained with the oxone-aldehyde-fuchsin-Halmi method. The results revealed that in all specimens where a regenerated periodontal ligament could be observed newly formed oxytalan fibers were present. They had a mainly apico-occlusal orientation and were localized closer to the cementum than to the alveolar bone. The regenerated oxytalan fibers had a similar morphological appearance than those observed in the original periodontal ligament regardless of the treatment modality by which regeneration was accomplished. Their presence was related to that of newly formed cementum suggesting a strong relationship between these 2 tissues. The neoformation of oxytalan fibres can thus be observed in some types of periodontal defects where the cementum and the periodontal ligament have been regenerated.

The purpose of the present study was to histologically assess the effect of enamel matrix derivative on periodontal regeneration in one human experimental defect. Experimental surgery was performed in a healthy male volunteer to create a buccal dehiscence defect in a mandibular incisor. Following bone removal and conditioning of the exposed root surface, enamel matrix derivative was applied onto the root surface. The flaps were then replaced and sutured. Clinical healing was uneventful. After 4 months, the experimental tooth together with the surrounding soft and hard tissues were removed surgically for histological evaluation. The microscopic examination revealed formation of a new acellular extrinsic fibre cementum, which was firmly attached to the underlying dentin. A new periodontal ligament with inserting and functionally-oriented collagen fibres and an associated alveolar bone was also present. The new cementum covered 73% of the original defect. Regain of bone was 65% of the presurgical bone height. It was concluded that adjunctive use of enamel matrix derivative could provide a regenerative technology with a potential for true periodontal regeneration.

Experimentation in animal models has created a basis for highly improved therapeutic procedures in reconstructive periodontal surgery. This symposium has discussed several animal models currently used; additional models have been described in recent literature. The presentations by Drs. Caton, Wikesjö, and Lynch illustrated the need for further discussion of some of the problems inherent in animal experimentation, including: standardization of periodontal defect configuration; adequate recording of preoperative attachment level; minimizing the effect of biological variability; use of surgically-created versus naturally-developed periodontal lesions; choice of observation period; and regenerative potential of the model chosen.

It is increasingly evident that controlled preclinical models with reproducible defect characteristics and biologic reaction are critical for evaluation of safety and efficacy of periodontal reconstructive protocols. Our investigations have characterized a supraalveolar periodontal defect in the mandibular premolar region in the beagle dog. This surgically-created critical size defect heals with almost complete connective tissue attachment following immediate reconstructive surgery. When the defect is exposed to periodontitis-simulating conditions prior to surgery the new connective tissue attachment is reduced. Bone and cementum regeneration is limited for both defect variations. Critical aspects relative to animal selection and management, surgical protocol, histologic and statistical analysis are discussed. This preclinical model has proven effective for evaluation of safety and efficacy of devices and biologics used adjunctive to periodontal reconstructive therapy.

Experimentally-produced defects in the non-human primate are preferred for testing the efficacy and safety of periodontal regenerative therapies. These animals closely resemble the human in dental anatomy and periodontal wound healing physiology. Defects can be produced which do not display spontaneous regeneration and which are contralaterally identical. Thus, within animals, untreated controls can be obtained to indicate the level of supporting tissues prior to therapy. The use of non-human primate models is recommended for science transfer experiments involving invasive surgery and the testing of potentially harmful new devices and pharmaceuticals.

Two commonly used animal models for evaluating putative periodontal regenerative therapies are the beagle dog model with natural periodontal disease and the non-human primate with ligature-induced attachment loss. The host response, microbiology, and skeletal rates of remodeling of these two models are summarized. In addition, the results of experiments comparing the healing response to periodontal surgery with and without concurrent use of the combination of platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) in these models are presented. At 1 month, PDGF/IGF-I administration resulted in a 64.1% and 51.4% increase in new attachment formation in the non-human primate and canine, respectively, while controls (surgery plus placebo) demonstrated 34.1% and 8.6% increases in new attachment formation in the non-human primate and canine models, respectively. Further, application of PDGF/IGF-I stimulated 21.6% and 65% osseous defect fill in the non-human primate and canine, respectively, while controls demonstrated 8.5% and 14.5% osseous defect fill in the non-human primate and canine, respectively. The osseous response in the canine appears greater than that of the non-human primate, and the new attachment formation was more substantial in the non-human primate than the canine. However, in general these data demonstrate a high degree of consistency in the effects of PDGF/IGF-I in promoting periodontal regeneration. Positive results in these two models--the dog with natural periodontal disease and the non-human primate with ligature-induced attachment loss--justify human clinical trial testing of a putative regenerative therapy.

The goal of periodontal treatments is the complete restoration of the structure and function of damaged periodontal tissues. Although it is very difficult to attain this goal, recent advances in periodontal wound healing concepts encourage hope of reaching it. Through reconsideration of the general concepts of wound healing and a review of the key and current literature on periodontal tissue regeneration, it is currently promised that this goal will be accomplished possibly by 1) spontaneous inherent tissue regeneration elicited by the elimination of causal factors; 2) guided tissue regeneration by the selective guidance of periodontal ligament cell proliferation; and 3) inductive tissue regeneration through recent advances in cellular biology.

It is known that periodontal tissues retain the ability to regenerate; however, current therapies fail in achieving predictable and consistent regeneration. Cell and molecular biology research in periodontal regeneration hold great promise in providing improved understanding of this complex phenomenon and direct us towards new possibilities of future clinical application. This paper reviews both the cells and extracellular matrix of the periodontal ligament in addition to the cell-to-matrix and cell-to-cell interaction involved in periodontal regeneration. Results of recent studies have suggested that periodontal regeneration recapitulates the process of morphogenesis, histogenesis, and cytodifferentiation, as well as cell field migration that occurs during development of the periodontium. A small population of purported periodontal stem cells is believed to be responsible for maintaining homeostasis in the periodontal ligament. This cell, which may have its origin in late periodontal mesenchyme of the dental papilla, is advocated as a tripotential cell capable of differentiating into cementoblast, osteoblast, and periodontal fibroblast. The clinical implication of advances made in cell and molecular biology research in periodontal regeneration may include future use of biomolecules in periodontal regeneration may include future use of biomolecules to improve the regenerative healing process and use of bioactive degradable membrane barriers in guided tissue regeneration as well as seeding of periodontal stem cells into periodontal defects. If the current trend continues, clinicians can look forward to seeing periodontal wound healing being substantially enhanced to achieve predictable periodontal regeneration.

Attempts at periodontal regeneration have been plagued by inconsistent results. The failures associated with these procedures are likely due to an insufficient number of cells themselves lacking sufficient activity to produce the supporting structures of the periodontium. Molecular studies have provided insight into the regenerative process by identifying locally acting mediators expressed during healing. These mediators, termed growth factors, may stimulate a wide variety of cellular events, including chemotaxis, proliferation, differentiation, and production of extracellular matrix proteins. Thus, the use of polypeptide hormones to enhance regeneration is based on the concept that the effect of the mediators that are naturally present can be enhanced by the addition of exogenous growth factors. Based on information originally obtained from in vitro studies, investigators have recently attempted to enhance bone formation and periodontal regeneration by using growth factors. This review focuses on five growth factor families that have potential for inducing periodontal regeneration based on their ability to stimulate osteoblasts and periodontal ligament cells in vitro or in vivo. These include platelet-derived growth factor, insulin-like growth factor, transforming growth factor-beta, fibroblast growth factor, and bone morphogenetic protein.

This summary focuses on quality of healing following periodontal surgical and non surgical procedures. It is based on a survey of the literature on clinical, radiographic and histological assessment as well as on 3 recent studies on the quality of periodontal healing published in this Journal.

The present study details the structural and ultrastructural features of healing events between the regenerated periodontal ligament and the root surface after experimental periodontal disease. Experiments were performed on dogs, and the concept of guided tissue regeneration was tested using resorbable polyurethane membranes. Light microscopy, scanning- and transmission electron microscopy were employed to determine if healing events involve regeneration (ie, process by which the architecture and the function are completely renewed) or periodontal repair (ie, healing of a wound by tissue that does not fully restore the architecture of a part). Regeneration occurred in parts of the roots only if some original cementum remained on the root surface after root planing. Repair was observed if peripheral dentin was removed by root planing as this layer was not reestablished. In areas remote from the base of the defect, new collagen fibrils, synthesized by fibroblasts and oriented perpendicular to the root surface, were spliced with severed ends of Sharpey's fiber bundles of original cementum. If circumpulpal dentin was exposed, intermingling between new fibrils with dentinal matrix fibrils occurred. In areas near the base of the defect, the first event was the formation of a cementoid by a cementoblast monolayer and subsequent formation of intrinsic fibrils oriented parallel to the root surface. Afterwards, the cementoblast monolayer disintegrated and extrinsic fiber bundles became anchored in the new cellular mixed fiber cementum. In these areas, linkage between new cementum and pre-existing tissues always occurred by interfacial intermingling of the fibrils, regardless of whether new attachment occurred at circumpulpal dentin or original cementum.

Techniques in treating periodontal disease are discussed to provide insight about which technique fits each clinical situation. New developments provide possible regeneration of new cementum, periodontal ligament and alveolar bone, resulting in a new periodontal attachment.

This paper reviews the current clinical and histologic literature in the field of periodontal regeneration. Various procedures and agents that have been used to attain regeneration and new attachment are reviewed, including open flap debridement, root conditioning, the use of bone grafts and bone substitutes, guided-tissue regeneration, coronally positioned flaps, and a combination of these. Future directions for clinical and research efforts are discussed, with emphasis on growth factors, their delivery, and enhancement of the healing response. Literature identifying factors that will aid in the regeneration of lost periodontium is reviewed and critiqued.

A multitude of new procedures and materials are being tested for their ability to promote periodontal wound healing. This review provides an overview of the most well-accepted methods for evaluating periodontal wound healing procedures/materials. Topics discussed include appropriate patient selection, general principles in non-surgical and surgical therapy as they relate to wound healing trials, clinical soft and hard tissue measurements which are generally obtained, an overview of radiographic assessments, and a discussion of the methods and role of histological evaluations in clinical trials. The advantages and disadvantages of the various methodologies are presented. The review concludes with the potential endpoints which can be used in periodontal wound healing studies.

Periodontal disease results in the gradual loss of supporting periodontal tissues, and ultimately, the teeth. Although conventional periodontal therapy can arrest the progression of the disease and allow healing, the resulting tissue is unlike that of the normal, healthy periodontium. Cellular and molecular biologic techniques may facilitate our understanding of the regeneration of the periodontium. This review discusses recent findings in cellular and molecular biology relevant to the biology of periodontal tissue regeneration.

Recent scientific advances have enabled scientists to understand some of the basic biological events leading both to an accelerated and improved healing of many tissues. These advances are now being applied to periodontal wound healing. Previous studies have indicated that various oncogenes are sequences related to growth factors and, that when these sequences are altered, cellular phenotype and especially cellular proliferation is altered. Data are presented using various human cell lines, including a c-myc-transfected periodontal ligament (PDL) cell line, which delineate the relationship between oncogenes, mRNA oncogene transcripts and polypeptide growth factors as inducers of cell phenotypic alterations, including adhesion, migration and proliferation. The polypeptide growth factors are a unique class of molecules that regulate cell phenotype both in vitro and in vivo. These demonstrable phenotypic conversions have indicated that such factors will play an important role in hard-soft tissue repair. Additionally, new data suggest that older PDL cells are not responsive to polypeptide stimulation; both the migratory and proliferative responses are diminished. A unique growth factor has been isolated and sequenced, which when applied to older PDL cells will reverse this refractory phenotype. These recent studies are extensively reviewed with emphasis and conclusions based on growth factor-induced periodontal regeneration. These studies stress the undeniable role that these novel approaches will have in future chairside periodontal practice.

This investigation assessed and compared the clinical efficacy of combined open flap debridement/occlusive membrane therapy versus open flap debridement therapy alone, in the treatment of maxillary periodontal furcation defects. Seventeen patients presenting with advanced adult periodontitis, including at least one pair of Class II maxillary furcal defects, comprised the study group. Following completion of a hygienic phase of treatment, measurements were made with calibrated periodontal probes to determine soft tissue recession, probing pocket depths, and attachment levels. Each pair of furcation defects was surgically exposed and hard tissue measurements obtained. Defects were treated with either open flap debridement and a polytetrafluoroethylene periodontal membrane or open flap debridement alone. Membranes were removed at 4 to 6 weeks. Six months postsurgery, soft tissue measurements were repeated and all sites were surgically re-entered to obtain hard tissue measurements. No statistically significant differences were found in recession, probing depth reductions, clinical attachment gains, or resorption of alveolar crest height between test and control groups. Results for these parameters were inconsistent and unpredictable. Statistically significant improvements were found, however, in horizontal open probing attachment (HOPA) and vertical open probing attachment (VOPA) between experimental and control sites. The GTR procedure as used in this study likely has limited application as a therapeutic modality for Class II furcations of maxillary molars. Modifications or improvements in the procedure may result in more predictable healing of these lesions.

This review discusses the rationale for using guided tissue regeneration therapy. The review not only attempts to clarify the concept of selective tissue regeneration using non-resorbable and resorbable barriers, but to discuss differences in healing events after treatment with the two types of barriers together with their significance in periodontal therapy. At present, barrier membranes have potential clinical use in promoting periodontal tissue regeneration if patients to be so treated are selected appropriately. Research is still necessary to determine the critical period for guiding the ingrowth of new attachment forming cells and also to further clarify the concept of GTR involving the "wrong cell type" which inhibits periodontal tissue regeneration.

Teflon membranes were interposed between soft tissue flaps and roots in 4 human suprabony lesions affecting the mandibular incisor teeth in 1 volunteer patient. 4 suprabony lesions affecting the mandibular incisor teeth were used as comparisons in a 2nd patient. All roots were debrided using ultrasonic and manual instruments and the most apical positioned calculus/site on the facial surface was notched. Flaps were sutured as coronally as possible using orthodontic brackets as anchors. Tissue blocks were removed 2 to 3 months after procedures and the facial aspects of all teeth were examined histologically. New attachment in the form of new "cementum with functionally oriented fibers" was seen within the calculus notch in 3 out of 4 membrane-treated sites and immediately apical to the notch at 1 site. The 4 comparison sites showed no evidence of new attachment within or adjacent to the notch. Rather, the gingival margins were located apical to the notch. Our observations suggest that guided tissue regeneration techniques improved coronal attachment responses in human suprabony lesions within the sample described.

A bio-resorbable type I collagen membrane was investigated as a barrier for guided tissue regeneration. Ten human subjects with at least one pair of contralateral periodontal lesions with probing pocket depths of greater than or equal to 5 mm and radiographic evidence of greater than or equal to 40% bone loss were included. Each patient underwent contralateral surgical flap procedures. A collagen barrier was adapted to the tooth in the experimental defect and the flap replaced and sutured. The controls consisted of the same procedure without the placement of the barrier. Standardized measurements of change in probing attachment levels and fill of intrabony defects were obtained at the time of surgery and 1 year later at the time of surgical re-entry. The differences in change of probing attachment levels and amount of bone fill between individual test and control sites were compared utilizing the student's t-test for paired samples. The mean probing attachment gain in the test sites was 0.56 +/- 0.57 mm, and there was a mean probing attachment loss of 0.71 +/- 0.91 mm in the control sites (P less than 0.01). The gain of bone in test lesions was 1.16 +/- 0.95 mm, while no gain was observed in the control lesions (P less than 0.01). The results of this study demonstrated that sites treated with a collagen barrier comprised of cross-linked bovine Type I collagen exhibited significantly better healing as compared to control sites over the 1-year period of the study.

In recent years a new technique in periodontal surgery, known as guided tissue regeneration, has been developed in Scandinavia and the USA. After raising a flap and debriding the root surface, an inert membrane is placed between the flap and the underlying tissues. This allows the periodontal ligament to regain some of the connective tissue attachment lost during the disease process, something which has been unobtainable until now. The purpose of this paper is to review the area of periodontal reattachment and to introduce the new technique of guided tissue regeneration.

The purpose of the present study was to determine whether the use of a porous hydroxylapatite in conjunction with guided tissue regeneration technique influenced the clinical results in the treatment of Class II furcation defects in humans. Fifteen subjects with a mean age of 39.4 +/- 9.3 years were used in this study. All subjects had Class II furcation defects on the buccal surfaces of 2 lower molars. In each subject one furcation defect was filled with granular porous hydroxylapatite and then a barrier of polytetrafluoroethylene periodontal material was positioned over the furcation. The other furca was treated in the same manner except that no hydroxylapatite was used. The flaps were placed coronally to their presurgical level. Before the surgery and 6 months postsurgery all areas were clinically evaluated using the same clinical parameters. Reentry procedures were used to repeat measurements of the osseous defects made during the initial surgery. At 6 months both surgical procedures resulted in statistically significant reduction in pocket depth and gain in probing attachment level with no significant difference between the two surgical procedures. When porous hydroxylapatite was used in conjunction with a polytetrafluoroethylene membrane, however, less gingival recession and more defect fill were obtained. This study suggests that there is a difference in healing of molar furcations when porous hydroxylapatite is used in conjunction with a barrier membrane. The lesions treated with porous hydroxylapatite gain in clinical attachment and horizontal and vertical bone fill, while the lesions treated with membrane only gain probing attachment with less bony fill.

The regenerative potential of the periodontal tissues in degree II and III furcation defects at mandibular molars was assessed in a clinical trial using a surgical treatment technique based on the principles of guided tissue regeneration. The patient sample included 37 subjects who had periodontal lesions in the right and left mandibular molar regions, including advanced periodontal destruction within the radicular area. Following a baseline examination, the furcation-involved molars were randomly assigned in each patient to either a test or a control treatment procedure. The test procedure included the elevation of mucoperiosteal flaps and the placement of a teflon membrane to cover the entrance of the furcation area and the adjacent root surfaces as well as a portion of the alveolar bone apical to the crest. The flaps were repositioned and secured with interdental sutures. A procedure identical to the one used at the test teeth was performed at the control tooth regions with the exception of the placement of the teflon membrane. Following surgery, all patients were placed on a plaque control regimen which involved daily rinsing with chlorexidine gluconate and, in addition, professional tooth cleaning once every 2 weeks for 6 months. After 6 months of healing, the test and control sites were re-examined. The findings demonstrated that the treatment of degree II furcation defects at mandibular molars using the principles of guided tissue regeneration in 19 sites out of 21 resulted in the resolution of the furcation defect. Conventional therapy reached the same goal in less than 20% of the cases treated.(ABSTRACT TRUNCATED AT 250 WORDS)

The capacity of collagen membranes to prevent the apical migration of epithelium and to support new connective tissue attachment was assessed in experimental periodontal defects in dogs. Experimental periodontal defects were produced in 8 mongrel dogs by removing the alveolar bone and the periodontal ligament over the most coronal 5 mm of the labial aspect of the maxillary canines. Experimental defects associated with the right canine and its surrounding bone were covered by collagen membranes prepared by air drying gels of rat type I fibrillar collagen. Flaps were repositioned and sutured. The contralateral control defects were sham-operated without using collagen membranes. Animals were killed, 10 and 30 days after surgery, 4 at each time point. The experimental and control sites were processed for histologic and histomorphometric evaluation. At 10 d, the average distance between the apical margin of the epithelium and the apical level of the defect (EA) sites was 3.20 +/- 0.55 mm for the experimental sites and 0.73 +/- 0.18 mm for the controls. The experimental root surfaces apical to the epithelium and the collagen membranes were covered by connective tissue cells. At 30 d, the EA for experimental and control sites were 2.55 +/- 0.36 mm and 0.47 +/- 0.30 mm, respectively. In the experimental sites healing by long junctional epithelium was observed in the coronal 40% of apico-occlusal dimension of the defect and new connective tissue attachment with inserting fibers in the apical 55% of the defect length. No new bone formation was observed. In the control sites, pocket formation was found in the most coronal one-third of the defect.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this investigation was to determine the histogenesis of periodontal regeneration using the principle of selective and guided cell repopulation of the root surface. A fenestration model, developed in the squirrel monkey, made it possible to exclude gingival epithelium and connective tissue and promote cell repopulation of the denuded root surface from the periodontal ligament and alveolar bone. Experimental and sham-operated control sites were compared histometrically after 3, 7, 14 and 35 days of healing. The results indicated that new cementum, bone and periodontal ligament formation occurred by the 14th day and that regeneration of the fenestration wound was almost complete by Day 35. Root resorption and ankylosis were observed in both experimental and sham-operated controls. There was significantly more periodontal regeneration in the experimental sites, which favored cell repopulation of the root surface from the periodontal ligament and alveolar bone.

An ultimate goal of periodontal therapy is predictable regeneration of a periodontium at the site of a previous marginal periodontitis. Current clinical therapeutic techniques result in repair, and not regeneration with formation of a new connective tissue attachment. Studies have indicated that surface demineralization of dentin from root surfaces predisposes toward a new connective tissue attachment, and this attachment may take place in an environment lacking periodontal progenitor cell populations. The rôle of the root surface is considered regarding inhibition and facilitation of these various connective tissue responses.

The current decline in the incidence of dental caries indicates that patients will retain most of their dentition. Reconstruction or regeneration of the entire attachment apparatus, including the periodontal ligament, cementum, and bone, is an attainable therapeutic goal. Clinical treatments designed to reattach connective tissue to exposed root surfaces commonly result in the formation of a long junctional epithelial attachment. This attachment is probably not an effective barrier to bacterial toxins and may allow recurrent pocket formation. To enhance reattachment of connective tissue, root-conditioning agents have been used but their clinical efficacy is questionable. Restoration of destroyed alveolar supporting bone by means of allogenic and autogenous bone-grafting materials has been recommended, but these procedures do not restore the cementum and PDL. Attempts to promote regeneration of the entire attachment apparatus have included clinical studies that used mechanical means to promote repopulation of affected root surfaces by periodontal ligament fibroblasts and prevent contact of epithelial or gingival connective tissue cells. Results thus far have been encouraging, but the practicality of these techniques may be limited. However, these studies have demonstrated that if only PDL cells contact the root surface during healing, a normal PDL can re-form. Dental follicle tissue is capable of inducing the formation of cementum-like structures and is clearly the cell population responsible for cementum and PDL formation. Recent research has demonstrated that the dental papilla probably shares the same inductive capabilities as the dental follicle.(ABSTRACT TRUNCATED AT 250 WORDS)