The Evolution of Surgical Techniques and Biomaterials for Periodontal Regeneration.

The understanding of biological concepts in wound healing together with the evolution in biomaterials applied in periodontal regeneration allowed for improved, minimally invasive surgical techniques with a wider range of application and adapted to achieve multiple goals at the same time. Regenerating attachment was never the sole end point, but maintaining the patient's own natural dentition in health and esthetics is becoming a feasible goal even in cases considered challenging just a few years ago. In this article we report on the evolution of techniques and biomaterials and their application in esthetic and challenging cases.

Interproximal attachment gain: The challenge of periodontal regeneration.

The new classification of periodontal diseases recognizes the key role of the interdental clinical attachment for defining the periodontal status and the extent of disease severity. Regenerating interdental clinical attachment not only improves the prognosis of the tooth, but it also lessens the severity of the disease condition. This manuscript provides a state-of-the-art review on surgical reconstructive approaches for treating papillary deficiency associated with soft and hard tissue interproximal defects. Combination therapy of papilla preservation, connective tissue grafting, and coronally advanced flaps may result in regeneration of the intrabony defect coupled with root coverage. Future research highlighted here may have the potential, especially in combination approaches, to repair challenging interproximal soft and hard tissue deficiencies.

Peri-implant Soft Tissue Management: Cairo Opinion Consensus Conference.

Peri-implant soft tissues play a role of paramount importance, not only on the esthetic appearance, but also on the maintenance and long-term stability of implants. The present report presents the conclusions from the Consensus Conference of the South European North African Middle Eastern Implantology & Modern Dentistry Association (SENAME) (4-6 November 2016, Cairo, Egypt). The conference focused on the topic of the soft tissue around dental implants, and in particular, on the influence of implant configurations on the marginal soft tissues, soft tissue alterations after immediate, early or delayed implant placement and immediate loading, the long-term outcomes of soft tissue stability around dental implants, and soft tissue augmentation around dental implants. Thirty world experts in this field were invited to take part in this two-day event; however, only 29 experts were in the final consensus voting process.

New Perspectives in the Use of Biomaterials for Periodontal Regeneration.

Periodontitis is a disease with a high prevalence among adults. If not treated, it can lead to loss of teeth. Periodontal therapy aims at maintaining patient's teeth through infection control and correction of non-maintainable anatomies including-when possible-regeneration of lost periodontal tissues. The biological regenerative potential of the periodontium is high, and several biomaterials can be utilized to improve the outcome of periodontal therapy. Use of different natural and synthetic materials in the periodontal field has been studied for many years. The main materials used today in periodontology analyzed in this review are: Resorbable and non-resorbable barrier membranes; autogenous, allogeneic, xenogeneic, and alloplastic bone substitutes; biological agents, such as amelogenins; platelet-derived growth factor; bone morphogenic proteins; rh fibroblast growth factor 2; teriparatide hormone; platelet concentrates; and 3D scaffolds. With the development of new surgical techniques some concepts on periodontal regeneration that were strictly applied in the past seem to be not so critical today. This can have an impact on the materials that are needed when attempting to regenerate lost periodontal structures. This review aims at presenting a rationale behind the use of biomaterials in modern periodontal regeneration.

CEMP-1 Levels in Periodontal Wound Fluid during the Early Phase of Healing: Prospective Clinical Trial.

OBJECTIVES: Cementogenesis seems to be significantly compromised during tissue inflammation. In dental practice, surgical procedures are performed with the aim to regenerate periodontium including cementum. However, inflammation that occurs during the initial healing phases after surgery may impair regeneration of this tissues. The aim of the present study was to assess if surgical procedures designed to regenerate periodontium might affect levels of cementum protein-1 (CEMP-1) in periodontal wound fluid during early phase of healing. MATERIALS AND METHODS: In 36 patients, 18 intrabony periodontal defects were treated with regenerative therapy (REG group) and 18 suprabony periodontal defects were treated with open flap debridement (OFD group). In the experimental sites, gingival crevicular fluid was collected immediately before surgery, and periodontal wound fluid was collected 4, 7, 14, and 21 days after surgery. CEMP-1 levels were detected by indirect enzyme-linked immunosorbent assay technique. RESULTS: At the analysis, it resulted that there was a significant average difference in CEMP-1 values between the REG and OFD groups at baseline (p = 0.041), the CEMP-1-modeled average in the OFD group was lower by 0.45 ng/ml. There was a significant trend in CEMP-1 over time, and this trend was different among the 2 groups: the REG group showed a statistically significant rising CEMP-1 trend (0.18 ng/ml a week p = 0.012), while the OFD had a trend that was significantly lower (-0.22 ng/ml a week compared to the REG group trend p = 0.023), the OFD group lost on average 0.05 ng/ml a week. In REG sites, GCF protein levels resulted also related to clinical parameters. CONCLUSIONS: During the initial inflammatory phase of periodontal healing, CEMP-1 levels decrease regardless of the surgical protocol applied. The surgical procedures used to regenerate periodontal tissue are able to reverse this trend and to induce significant increase of CEMP-1 in periodontal wound fluid after the first week postop.

Minimizing Patient Morbidity Following Palatal Gingival Harvesting: A Randomized Controlled Clinical Study.

This clinical study was conducted to evaluate the impact of different hemostatic treatments following palatal gingival harvesting on patient discomfort. Fifty patients who needed a mucogingival surgery requiring gingival graft harvesting were enrolled and randomly assigned to one of five groups: (1) a control group in which only sutures were applied; (2) a cyanoacrylate group; (3) a periodontal dressing material group; (4) a hemostatic gelatin sponge group; and (5) a group in which the gelatin sponge and cyanoacrylate were combined. In the 2 weeks following the procedures, perception of pain, healing, consumption of drugs, and willingness to repeat the procedure were recorded through visual analog scale (VAS) by patients. Over the 2 weeks, lower pain (VAS) was found in all test groups compared to the control group (P < .01, value for time-group interaction). Notably, the gelatin sponge combined with cyanoacrylate group had very low pain (VAS ≤ 0.5 points) throughout the 14 days. The lowest healing scores at day 10 were associated with the control group (6.8 VAS points) in contrast to the four test groups (8.2 to 9.0 VAS points, P = .0001). Pain was inversely correlated with age (P < .05). Pain also depended on the apicocoronal dimension of the graft: the higher the graft, the more pain was experienced by the participants (0.4 VAS points per 1 mm, P < .05). Within the limitations of this study, palatal coverage appears to result in better outcomes when compared to suture alone. In particular, a double-layered protection of the palatal wound with a gelatin sponge combined with cyanoacrylate appeared to be the best option in reducing pain and postoperative discomfort.

Predictor factors for long-term outcomes stability of coronally advanced flap with or without connective tissue graft in the treatment of single maxillary gingival recessions: 9 years results of a randomized controlled clinical trial.

AIM: To assess the clinical outcomes 9 years after the surgical treatment of single maxillary gingival recessions and identify predictors for long-term gingival margin stability. MATERIALS AND METHODS: Twenty-five gingival recessions (Miller Class I and II) were randomly treated with Coronally Advanced Flap (CAF) plus Connective Tissue Graft (CTG) or CAF alone. Outcomes included complete root coverage (CRC), recession reduction (REC), keratinized tissue (KT) gain and dentin hypersensitivity, and were evaluated at 6 months, 1 and 9 years. Multilevel analysis was performed to identify predictors for long-term gingival margin stability. RESULTS: Baseline gingival recession was 2.4 ± 0.8 mm and 2.4 ± 1.0 mm in the CAF + CTG and in the CAF-treated sites, respectively (p = 0.693). The chance to gain and preserve CRC over time is equal to 70% in the CAF + CTG group (Relative Risk [RR] = 1.70, 95% CI [0.84-3.45]; adjusted RR = 1.48, 95% CI [0.61-3.62]). Using the CTG, an increase in KT was recorded 9 years after the surgery (p = 0.019). An OR of 0.12 (p = 0.022) of not achieving CRC was observed in cases with non-carious cervical lesions (NCCL) compared to cases without NCCL. CONCLUSION: Both treatment modalities demonstrated stability over time. Additional use of CTG provided a greater increase in KT. The presence of NCCL negatively affected CRC and REC.

Impact of Dental Implant Surface Modifications on Adhesion and Proliferation of Primary Human Gingival Keratinocytes and Progenitor Cells.

The success of dental implants depends mainly on osseointegration and gingival sealing. Therefore, early attachment and spreading of epithelial cells might be critical for a positive outcome. Research in dental implant materials has primarily focused on surface roughness, defined by the average roughness (Ra) index, as it promotes the process of osseointegration. This study explored its influence on soft tissue attachment by looking mainly at adhesion, proliferation, and spreading of primary human cells belonging to the epithelial lineage. Characterized human gingival keratinocytes, gingival and epithelial progenitor cells were seeded on machined (S1; Ra = 0.3 to 0.6 µm), Ti-Unite (S2; Ra = 1.2 µm), and SLA (S3; Ra = 2 µm) implants. Cell adhesion with early proliferation and spreading were evaluated by combining a biochemical vitality test with imaging analyses. Findings showed that adhesion was significantly higher on S1 (36% ± 2%) and S2 (44% ± 7%) than on S3 (23% ± 6%), while early proliferation was slightly improved on S1. The resulting data, obtained through an innovative and easily reproducible in vitro method, suggest that implant surface roughness affects epithelial cell adhesion and proliferation.

Using MicroCT to Assess Periodontal Regeneration Outcomes-Comparison of Image-Based and Histologic Results: A Case Report.

The purpose of this study was to compare microcomputed tomography (microCT) and histologic analysis outcomes of a periodontal regeneration of a human defect treated with a polylactic- and polyglycolic-acid copolymer. At 11 months following the grafting procedure, the root with the surrounding periodontal tissues was removed and analyzed using microCT and histologic techniques. The results suggest that microCT three-dimensional analysis may be used in synergy with two-dimensional histologic sections to provide additional information for studying the regeneration outcomes normally reported by histologic biopsies in humans. Additional data is needed to validate these findings.

Evaluation of DNA methylation of inflammatory genes following treatment of chronic periodontitis: A pilot case-control study.

OBJECTIVE: To evaluate the influence of periodontal therapy on DNA methylation in patients with chronic periodontitis as compared to healthy individuals. MATERIAL AND METHODS: Twenty patients were enrolled into two groups: (i) 10 diagnosed as clinically healthy; and (ii) 10 diagnosed with chronic periodontitis. Clinical measures were recorded and gingival biopsies were harvested at baseline (both patient groups) and at 2 and 8 weeks post-baseline for diseased individuals. Molecular DNA methylation analysis was performed by pyrosequencing for the putative inflammation-associated genes LINE-1, COX-2, IFN-γ and TNF-α. Random-intercept linear regression models were applied to evaluate methylation levels across groups at baseline and the methylation changes over time in the diseased and normal tissues. RESULTS: Periodontal therapy did not influence gene expression methylation of TNF-α, IFN-γ and LINE-1 levels at normal and periodontitis sites over time. However, it significantly reduced COX-2 methylation levels comparable to healthy individuals at both 2 and 8 weeks post-treatment (p < .05). CONCLUSIONS: Periodontal therapy resets the DNA methylation status of inflammatory gene for COX-2 in patients with periodontal disease. DNA methylation levels of TNF-α, IFN-γ and LINE-1 were sustained in periodontitis sites despite therapy. Future studies should consider an expanded panel of inflammatory genes over time. (ClinicalTrials.gov NCT02835898).

Gingival Margin Stability After Mucogingival Plastic Surgery. The Effect of Manual Versus Powered Toothbrushing: A Randomized Clinical Trial.

BACKGROUND: Oscillating-rotating power toothbrushes have been proven to be clinically efficacious. To the best of the authors' knowledge, a clinical evaluation of the safety of these toothbrushes after surgical root coverage procedures has not been published. The aim of this study is to evaluate the gingival margin (GM) stability with the use of an oscillating-rotating toothbrush compared with a manual toothbrush. METHODS: Sixty healthy individuals with at least one Miller Class I or II gingival recession underwent a surgical root coverage procedure. Soft-bristle manual and powered toothbrushes were given to participants randomly assigned to control and test groups, respectively. Full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), probing depth (PD), and recession depth (RD) were recorded at baseline and 1, 3, and 6 months after completion of the surgical procedure. Data analyses were performed using linear random-intercept models to take into account within-participant correlations over time. Temporal trend differences across treatments by including treatment-time interaction terms were then tested using a global Wald test. RESULTS: Use of a powered toothbrush resulted in a significantly greater reduction of recorded periodontal clinical indices compared with a manual device (FMPS, P = 0.05; FMBS, P = 0.005; RD, P = 0.004). No significant differences were noticed between the two experimental groups both for PD (P = 0.03) and clinical attachment level (P = 0.11). Complete root coverage was significantly higher in participants who used the powered toothbrush compared with the manual toothbrush at 6 months (control, 66.67%; test, 96.67%; P = 0.002). CONCLUSION: Use of an oscillating-rotating powered toothbrush with a soft-bristle head resulted in higher GM stability after root coverage procedures compared with the use of a manual soft-bristled toothbrush.

3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications.

To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the quality of bone formation. To overcome the drawbacks of routinely employed grafting materials, bone graft substitutes such as 3D scaffolds have been recently investigated in the dental field. In this review, we highlight different biomaterials suitable for 3D scaffold fabrication, with a focus on "3D-printed" ones as bone graft substitutes that might be convenient for various applications related to implant therapy. We also briefly discuss their possible adoption for periodontal regeneration.

Impact of Orthodontic Treatment on Periodontal Tissues: A Narrative Review of Multidisciplinary Literature.

The aim of this review is to describe the most commonly observed changes in periodontium caused by orthodontic treatment in order to facilitate specialists' collaboration and communication. An electronic database search was carried out using PubMed abstract and citation database and bibliographic material was then used in order to find other appropriate sources. Soft and hard periodontal tissues changes during orthodontic treatment and maintenance of the patients are discussed in order to provide an exhaustive picture of the possible interactions between these two interwoven disciplines.

Pre-augmentation soft tissue expansion: an overview.

OBJECTIVES: The aim of this study was to explore the development of soft tissue expanders, their different types and their potential applications prior to bone augmentation and implant placement. MATERIAL AND METHODS: A review of pertinent literature was performed using PubMed to comprehend the dynamics of soft tissue expanders and determine the current position of their pre-augmentation applications. RESULTS: There is promising, albeit preliminary information regarding the benefits of pre-augmentation soft tissue expansion. Findings cannot be generalised due to relatively small sample size. CONCLUSIONS: Further clinical trials with larger sample sizes and long-term follow-up are needed before soft tissue expanders can be confidently applied in everyday clinical practice.

Modified double papillae flap technique: a new surgical approach for the treatment of isolated gingival recession defects. A case series.

AIM: There have been no modifications made to the original double papillae flap surgical technique introduced by Cohen and Ross in 1968. The aim of the present case series is to evaluate the effectiveness of a modified surgical approach to the double papillae flap design in the treatment of isolated gingival recession. MATERIALS AND METHODS: A total of 12 healthy, young patients (age range 20 to 28 years) with isolated gingival recession were enrolled in this study. The gingival recession had the following characteristics: isolated defect, Miller Class I or II defect, visible cementoenamel junction (CEJ), and well represented interdental papillae. The following clinical measurements were taken before the surgery and at the 1-year follow-up examination: probing depth (PD) at the treated tooth, clinical attachment level (CAL), amount of keratinized tissue (KT) at the treated site, and recession depth (RD). All measurements were taken at baseline and after 12 months by means of a manual probe and were rounded up to the nearest millimeter. RESULTS: At the 1-year follow-up examination, the same clinical parameters taken at baseline were rerecorded. No statistical differences were noted for the PD (P=0.54). The mean increase for the CAL was statistically significant (P=0.04). Furthermore, the mean amount of KT increased by 2.5±0.4 mm (P<0.001). Finally, the mean RD decreased to 0.5±0.6 mm, corresponding to a root coverage of 3.8±0.8 mm (P<0.001). In terms of mean root coverage (MRC), 88.4% of exposed root surface was covered with soft tissue, and 9 of the 12 treated teeth (75%) showed complete coverage of the root surface. CONCLUSION: The results of the present case series show that the modified double papillae flap technique is effective in obtaining root coverage of isolated gingival recession defects. These rootcoverage outcomes were associated with clinically and statistically highly significant clinical attachment gain, with no noticeable change in either the PD values or the height of KT on the buccal aspect of the treated teeth.

Surgical Approaches Based on Biological Objectives: GTR versus GBR Techniques.

Guided tissue regenerative (GTR) therapies are performed to regenerate the previously lost tooth supporting structure, thus maintaining the aesthetics and masticatory function of the available dentition. Alveolar ridge augmentation procedures (GBR) intend to regain the alveolar bone lost following tooth extraction and/or periodontal disease. Several biomaterials and surgical approaches have been proposed. In this paper we report biomaterials and surgical techniques used for periodontal and bone regenerative procedures. Particular attention will be adopted to highlight the biological basis for the different therapeutic approaches.

The soft tissue wall technique for the regenerative treatment of non-contained infrabony defects: a case series.

The ability to stabilize the blood clot is crucial in achieving predictable periodontal regeneration in infrabony defects. Unfortunately, micromovements may cause degradation of the clot-root interface and result in suboptimal wound healing. Current surgical and suturing techniques are aimed at reducing flap micromovement because flap management is one of the main factors influencing the stability of the clot. The aim of this paper is to describe the use of the soft tissue wall technique to enhance periodontal tissue regeneration outcomes of challenging non-contained infrabony defects. Nine one-wall infrabony defects were treated with a combination of a papilla preservation technique and a coronally advanced flap. Enamel matrix derivative was delivered to the defect, but no bone grafting materials or membranes were employed. Mean 1-year probing depth reduction was 6.3 ± 2.0 mm (P < .001) and mean clinical attachment gain was 7.1 ± 1.0 mm (P < .001). All treated sites showed a mean reduction of exposed root surface equal to 1.0 ± 0.4 mm (P = .05). The results suggest the possibility of improving the regenerative potential of a one-wall infrabony defect by the creation of a stable soft tissue wall while also enhancing the esthetic outcome of the surgical procedure. Further studies with a larger number of patients are needed to support these preliminary data.

Stem cell therapy for craniofacial bone regeneration: a randomized, controlled feasibility trial.

Stem cell therapy offers potential in the regeneration of craniofacial bone defects; however, it has not been studied clinically. Tissue repair cells (TRCs) isolated from bone marrow represent a mixed stem and progenitor population enriched in CD90- and CD14-positive cells. In this phase I/II, randomized, controlled feasibility trial, we investigated TRC cell therapy to reconstruct localized craniofacial bone defects. Twenty-four patients requiring localized reconstruction of jawbone defects participated in this longitudinal trial. For regenerative therapy, patients were randomized to receive either guided bone regeneration (GBR) or TRC transplantation. At 6 or 12 weeks following treatment, clinical and radiographic assessments of bone repair were performed. Bone biopsies were harvested and underwent quantitative micro-computed tomographic (µCT) and bone histomorphometric analyses. Oral implants were installed, subsequently restored, and functionally loaded with tooth restorations. Reconstructed sites were assessed for 1 year following therapy. No study-related, serious adverse events were reported. Following therapy, clinical, radiographic, tomographic, and histological measures demonstrated that TRC therapy accelerated alveolar bone regeneration compared to GBR therapy. Additionally, TRC treatment significantly reduced the need for secondary bone grafting at the time of oral implant placement with a five fold decrease in implant bony dehiscence exposure (residual bone defects) as compared to GBR-treated sites(p < 0.01). Transplantation of TRCs for treatment of alveolar bone defects appears safe and accelerates bone regeneration, enabling jawbone reconstruction with oral implants. The results from this trial support expanded studies of TRC therapy in the treatment of craniofacial deformities (ClinicalTrials.gov number CT00755911).

Postextraction alveolar ridge preservation: biological basis and treatments.

Following tooth extraction, the alveolar ridge undergoes an inevitable remodeling process that influences implant therapy of the edentulous area. Socket grafting is a commonly adopted therapy for the preservation of alveolar bone structures in combination or not with immediate implant placement although the biological bases lying behind this treatment modality are not fully understood and often misinterpreted. This review is intended to clarify the literature support to socket grafting in order to provide practitioners with valid tools to make a conscious decision of when and why to recommend this therapy.

Analysis of tissue neogenesis in extraction sockets treated with guided bone regeneration: clinical, histologic, and micro-CT results.

The aims of this article were to perform a detailed evaluation of the healing of extraction sockets covered with a resorbable collagen membrane 12 weeks following exodontia and to determine if this device had ossifying properties. Ten consecutive subjects in need of extraction of maxillary premolars were recruited. Each subject had a hopeless maxillary premolar extracted with minimal trauma. Sockets were then covered with a collagen barrier membrane alone. At 12 weeks, reentry surgery was performed, clinical measurements were repeated, and bone core biopsies were obtained prior to dental implant placement for histologic and microcomputed tomography (micro-CT) analysis. Study sites showed mean bone regeneration horizontally of 7.7 mm (buccopalatally) and 4.6 mm (mesiodistally). Vertical bone repair showed a mean gain of 10.9 mm. Subtraction radiography showed a mean apical shift of the crestal bone at the center of the socket of 2.1 mm (range, 0.7 to 4.3 mm). Micro-CT and histology revealed formation of well-mineralized tissue at 12 weeks, with a mean percentage of vital bone of 45.87% ± 12.35%. No signs of membrane ossification were observed. A detailed analysis of tissue neogenesis in extraction sites protected by this barrier membrane has demonstrated that adequate bone formation for implant placement occurs as early as 12 weeks following exodontia, with minimal changes in alveolar ridge dimensions. No evidence of membrane ossification was observed.