Modulation of regenerative responses by retinoic and ascorbic acids in human apical papilla cells.

OBJECTIVE: This study investigated the bioactive effects of retinoic acid and ascorbic acid on hSCAPs in vitro. DESIGN: Cells were obtained from human third molars (n=4) and characterized for mesenchymal stem cell markers by flow cytometry. The experimental groups: control (α-MEM); vehicle control group (α-MEM + 0.17 % DMSO); retinoic acid 0.1, 1, and 10 µM; and ascorbic acid 3, 30, and 300 µM (n=8) were tested for cell viability (alamarBlue; 1, 3, and 7 days), total collagen synthesis (Sirius Red; 1 and 7 days), mineralized matrix formation (Alizarin red; 14 days), and the regulation of gene expression related to mineralization (ALPL and DSPP), cell migration (ITGAV and CXCL12) angiogenesis (VEGFA) and collagen synthesis (COL1A1 and COL3A1; RT-qPCR) on 1 and 7 days. ACTB and GAPDH were used as reference genes. Data were analyzed by ANOVA and complementary tests at a 5 % significance level. RESULTS: Ascorbic acid 300 µM increased viability, and retinoic acid reduced it dose-dependently. Retinoic acid 0.1 µM and ascorbic acid 30 and 300 µM increased mineralized matrix formation and total collagen synthesis, and retinoic acid 10 µM decreased. On day 1, 0.1 µM retinoic acid upregulated the gene expression of COL1A1, COL3A1, VEGFA, CXCL12, ALPL, DSPP e ITGAV, and 300 µM ascorbic acid upregulated COL1A1, COL3A1 and DSPP. However, on day 7, retinoic acid downregulated ALPL, COL3A1, CXCL12, and VEGFA and downregulated ITGAV and VEGFA. CONCLUSION: Retinoic acid 0.1 µM and ascorbic acid 300 µM biostimulated hSCAPs to differentiate into pro-regenerative phenotypes with potential application for REPs.

Introduction and overview on autogenous Platelet concentrates.

This special issue on autologous platelet concentrates (APCs) provides clinicians with an overview on the current understanding of the use of these biomaterials for soft and hard-tissue regeneration. The included papers summarize scientific evidence and the clinical findings, presented in simple tables that outline potential benefits including Patient Reported Outcome Measures (PROMs). This approach enables clinicians to assess clinical relevance and researchers to identify significant gaps in the literature. The first part provides a comprehensive summary of the basic science surrounding APC, with particular focus on their preparation methods. Clear recommendations are outlined, which are crucial for obtaining high-quality APCs, alongside an exploration of how APCs may influence both soft and hard tissue healing processes. Part 2 delves into the clinical evidence for the potential benefits of APCs across a range of applications: alveolar ridge preservation, sinus floor elevation, periodontal plastic surgery, guided tissue regeneration, guided bone regeneration, the healing of Medication-Related Osteonecrosis of the Jaw (MRONJ), and endodontic surgery. In the part 3, the discussion turns to the effects of APCs on the healing of extra-oral wounds, including diabetic foot ulcers, venous leg ulcers, pressure injuries, burns, and more. For those clinicians persuaded by the evidence, the fourth section offers a detailed, step-by-step flowchart for each treatment modality, providing a clear guide for clinical application.

Polycaprolactone/gelatin/ZIF-8 nanofiber membrane for advanced guided tissue regeneration in periodontal therapy.

The periodontal tissue regeneration strategy based on guided tissue regeneration (GTR) membranes is an effective therapy for periodontal defects. Traditional GTR membranes, however, primarily serve as physical barriers and lack antimicrobial and osteogenic functions. Herein, we developed a multifunctional nanofiber membrane with zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded in a hydrophilic gelatin layer. The release of Zn2+ from the ZIF-8 NPs effectively promoted bone tissue repair and simultaneously enabled GTR membranes with >99 % antibacterial efficacies against Escherichia coli and Staphylococcus aureus. Additionally, the incorporation of gelatin enhances cellular adhesion and growth. Furthermore, in vivo studies revealed significant bone regeneration, with increased trabecular number and reduced separation. Owing to its multiple functions, excellent biocompatibility and desirable mechanical properties, this membrane has considerable potential in the field of periodontal therapy.

Use of autologous micrografts associated with xenogeneic anorganic bone in vertical bone augmentation procedures with Barbell Technique®.

INTRODUCTION: Bidirectional vertical ridge augmentation in the posterior maxilla is very challenging. PURPOSE: To evaluate the regenerative potential of micrografts, derived from periosteum or bone tissue, added to an anorganic xenograft in vertical reconstruction of the posterior maxilla, by a prospective, controlled study. MATERIALS AND METHODS: After clinical selection and the analysis of CBCT scans, 24 posterior maxillary sites, in 19 patients, were treated by using Barbell Technique®. Sites requiring both inlay and onlay reconstruction were enrolled in the study. In the Control Group (CG, n = 8), a xenograft was used in the inlay site and for the onlay site, a 1:1 mix of xenograft and an autograft was used. In Test Group 1 (TG1, n = 8), both inlay and onlay sites were grafted with the xenograft associated with the micrografts derived from periosteum. In Test Group 2 (TG2, n = 8), both inlay and onlay sites were grafted with the xenograft associated with the micrografts derived from bone. Six months after the procedures, CBCT scans were obtained, and bone biopsy samples were harvested during implant placement surgery. The bone specimens were analyzed histomorphometrically, by measuring the percentages of vital mineralized tissue (VMT), non vital mineralized tissue (NVMT) and non mineralized tissue (NMT). Immunohistochemically, the levels of VEGF were categorized by a score approach. RESULTS: Histomorphometric analysis revealed, for the inlay grafts, no significant difference among the groups for VMT, NVMT and NMT. However, for onlay grafts, CG achieved a higher amount of VMT in comparison with TG2, and the opposite occurred for NMT values. In this regard, no statistical difference was observed between CG and TG1. Concerning immunohistochemistry, the VEGF values for CG and TG1 were slightly higher than those obtained by TG2 for both inlay and onlay grafts, but without statistical significance. CBCT analysis showed a similar level of gain for all groups, for both inlay and onlay bone augmentation sites. Clinically, one implant (in CG) within a total of 50 implants installed, had early failure and was replaced after 3 months. All patients received implant supported prosthesis. CONCLUSION: This study indicated that the clinical use of micrograft derived from periosteum may have some potential to increase bone formation in onlay reconstructions, unlike the micrograft derived from bone tissue.

Autologous micrografting improves regeneration of tissue-engineered urinary conduits in vivo.

Urogenital reconstructive malformation surgery is sometimes hampered by lack of tissue for the repair. We have previously shown that autologous micrografting allows for single-staged scaffold cellularization after surgical implantation. Here, a collagen-based scaffold reinforced with biodegradable mesh and a stent was implanted as a bladder conduit in ten full-grown female minipigs. We aimed to assess short-term regenerative outcomes, safety, and feasibility of implanting tubular urinary micrografted scaffolds versus acellular controls. Five scaffolds were embedded with autologous urothelial micrografts harvested perioperatively. After six weeks, all animals were assessed by cystoscopy, CT-urography, and microanatomical assessment of the urinary conduits. The procedure proved technically feasible within the confines of a regular surgical theater, with duration-times comparable to corresponding conventional procedures. No animals experienced postoperative complications, and all implanted conduits were patent at follow-up. Improved tissue regeneration was observed in the micrografted conduits compared with the acellular controls, including increased luminal epithelialization, increased cell proliferation, decreased cell apoptosis, and increased conduit vascularization. We concluded that single-staged on-site construction and implantation of tissue engineered urinary conduits proved feasible and safe, with improved regenerative potentials in micrografted conduits. This study presents a new approach to urinary conduits, and merits further investigations for advancement towards clinical translation.

Reviewing the benefits and clinical outcomes of oral fibroblasts over mesenchymal stem cells for repairing periodontal defects during or after orthodontic tooth movement.

Orthodontic therapy applies forces to teeth, causing an inflammatory reaction in the periodontal ligament. This is repaired by remodeling of the periodontium, allowing tooth displacement. Although orthodontic therapy is mostly initiated during childhood and adolescence, the number of adults seeking this treatment is increasing as our society's esthetic awareness rises. However, adults may already have periodontal tissue abnormalities, rendering orthodontic treatment inefficient because a healthy periodontium is essential for success. Numerous risk factors have been linked to periodontal lesions, with orthodontic tooth movement possibly playing a minimal influence. Although such tissue damages are mostly of esthetic rather than functional concern for patients, restoration frequently requires invasive procedures. Autologous cells for the treatment of periodontal complications have grown in popularity as a less intrusive alternative. The present review analyzed the literature on the use of mesenchymal stem cells and oral tissue-derived fibroblasts for the healing of periodontal defects that may be related to orthodontic tooth movement. Furthermore, the advantages and challenges of the two cell types have been examined. Although the number of clinical studies is currently limited, our study demonstrates that oral fibroblasts have the potential to be the next emergent frontrunners for tissue engineering in the periodontium.

Clinical efficacy of periosteal pedicle graft as a barrier membrane in guided tissue regeneration: A systematic review and meta-analysis.

Background: The study aims to assess the clinical efficacy of periosteal pedicle graft (PPG) as a barrier membrane in guided tissue regeneration (GTR) for gingival recession, intrabony, and furcation defects. Materials and Methods: Electronic and hand searches were performed to identify randomized controlled/clinical trials investigating GTR using PPG, with 6-month follow-up. Primary outcomes recorded: probing depth (PD), clinical attachment level (CAL), bone fill, recession depth (RD) reduction, percentage of mean root coverage, keratinized tissue width (KTW), and bone defect area (BDA). Results: Thirteen articles were selected; 6 for recession, 2 for furcation, and 5 for intrabony. Meta-analysis was performed whenever possible, results expressed as pooled standardized mean differences (SMDs). In recession defects, the RD pooled SMD is 0.47 (95% confidence interval (CI) = [-0.50-1.44]), KTW pooled SMD is 1.30 (95% CI = [-0.30-2.91]), favoring PPG over the comparator. In furcation defects, PD pooled SMD is 1.12 (95% CI = [-2.77-0.52]), CAL pooled SMD is 0.71 (95% CI = [-1.09-2.50]), and bone fill pooled SMD is 0.67 (95% CI = [-3.34-4.69]) favoring PPG. In intrabony defects, PD pooled SMD is 0.54 (95% CI = [-2.12-1.04]), CAL pooled SMD is 0.23 (95% CI = [-1.13-0.68]), and BDA pooled SMD is 0.37 (95% CI = [-1.58-2.31]) favoring PPG. The results were not statistically significant. Conclusion: The current evidence indicates that PPG constitutes a valid and reliable alternative to collagen barrier membranes for successful GTR.

Novel collagen gradient membranes with multiphasic structures: Preparation, characterization, and biocompatibility.

Scaffolds with multiphasic structures are considered to be superior for guided tissue regeneration. Two types of tilapia skin collagen gradient membranes (stepped gradient and linear gradient) with multiphasic structures were prepared by controlling the collagen concentrations and the freezing rates. The results revealed that collagen gradient membranes were more capable of guiding tissue regeneration compared to homogeneous membranes. These two gradient membranes featured a dense outer layer and a loose inner layer, with good mechanical properties as indicated by tensile strengths of more than 250 Kpa and porosities exceeding 85 %. Additionally, these membranes also showed good hydrophilicity and water absorption, with an inner layer contact angle of less than 91° and a water absorption ratio greater than 40 times. Furthermore, the multiphasic scaffolds were proved to be biocompatible by the acute toxicity assay, the intradermal irritation test and so on. Gradient membranes could effectively promote the adhesion and proliferation of fibroblasts and osteoblasts, through elevating the TGF-ß/Smad signaling pathway by TGF-ß and Smads, and activating the Wnt/ß-catenin signaling pathway by LRP5 and ß-catenin, similar to homogenous membranes. Therefore, collagen gradient membranes from tilapia skin show important application value in guiding tissue regeneration.

Nanoparticles in Periodontitis Therapy: A Review of the Current Situation.

Periodontitis is a disease of inflammation that affects the tissues supporting the periodontium. It is triggered by an immunological reaction of the gums to plaque, which leads to the destruction of periodontal attachment structures. Periodontitis is one of the most commonly recognized dental disorders in the world and a major factor in the loss of adult teeth. Scaling and root planing remain crucial for managing patients with persistent periodontitis. Nevertheless, exclusive reliance on mechanical interventions like periodontal surgery, extractions, and root planning is insufficient to halt the progression of periodontitis. In response to the problem of bacterial resistance, some researchers are committed to finding alternative therapies to antibiotics. In addition, some scholars focus on finding new materials to provide a powerful microenvironment for periodontal tissue regeneration and promote osteogenic repair. Nanoparticles possess distinct therapeutic qualities, including exceptional antibacterial, anti-inflammatory, and antioxidant properties, immunomodulatory capacities, and the promotion of bone regeneration ability, which made them can be used for the treatment of periodontitis. However, there are many problems that limit the clinical translation of nanoparticles, such as toxic accumulation in cells, poor correlation between in vitro and in vivo, and poor animal-to-human transmissibility. In this paper, we review the present researches on nanoparticles in periodontitis treatment from the perspective of three main categories: inorganic nanoparticles, organic nanoparticles, and nanocomposites (including nanofibers, hydrogels, and membranes). The aim of this review is to provide a comprehensive and recent update on nanoparticles-based therapies for periodontitis. The conclusion section summarizes the opportunities and challenges in the design and clinical translation of nanoparticles for the treatment of periodontitis.

Treatment of a Localized Stage III Periodontitis in the Esthetic Zone with Guided Tissue Regeneration Technique on a Heavy Smoker Patient with 12-Year Follow- up: A Case Report.

This case report exhibits a heavy smoker female patient with a localized stage III periodontitis who has been under the smoking cessation program during the pre-surgical period, followed by a strict maintenance program for the past twelve years, after being treated with guided tissue regeneration techniques and restored with zirconia prosthetic crowns. A 50-year-old, heavy smoker (> 40 cigarettes per day), systemically healthy female patient presented complaining of mobility and pain in the upper right central incisor, which was temporarily splinted to the left central incisor using resin composite. After clinical and radiographic examination, significant damage of the attachment apparatus, deep periodontal lesions extending the middle portion of the root, and severe infrabony defect were noted. Following the initial hygienic phase, a guided tissue regeneration surgery using xenograft bone substitute covered by a resorbable collagen membrane was performed. After six months of healing, four zirconia crowns were cemented on the central and lateral incisors based on patient esthetic compliance. During the 12-year follow-up period, neither residual pockets nor gingival recession were observed, and perfect marginal bone stability, and esthetic and functional results were noted. This case shows the predictability of a conservative surgical technique, the guided tissue regeneration, based on appropriate treatment planning and a strict maintenance program. It also demonstrates the importance of at least a 6-month healing period after such surgeries, allowing complete tissue maturation and a re-establishment of the supra osseous gingival tissues in order to locate the prosthetic margins without interfering with the soft tissues integrity.

Developments in Alloplastic Bone Grafts and Barrier Membrane Biomaterials for Periodontal Guided Tissue and Bone Regeneration Therapy.

Periodontitis is a serious form of oral gum inflammation with recession of gingival soft tissue, destruction of the periodontal ligament, and absorption of alveolar bone. Management of periodontal tissue and bone destruction, along with the restoration of functionality and structural integrity, is not possible with conventional clinical therapy alone. Guided bone and tissue regeneration therapy employs an occlusive biodegradable barrier membrane and graft biomaterials to guide the formation of alveolar bone and tissues for periodontal restoration and regeneration. Amongst several grafting approaches, alloplastic grafts/biomaterials, either derived from natural sources, synthesization, or a combination of both, offer a wide variety of resources tailored to multiple needs. Examining several pertinent scientific databases (Web of Science, Scopus, PubMed, MEDLINE, and Cochrane Library) provided the foundation to cover the literature on synthetic graft materials and membranes, devoted to achieving periodontal tissue and bone regeneration. This discussion proceeds by highlighting potential grafting and barrier biomaterials, their characteristics, efficiency, regenerative ability, therapy outcomes, and advancements in periodontal guided regeneration therapy. Marketed and standardized quality products made of grafts and membrane biomaterials have been documented in this work. Conclusively, this paper illustrates the challenges, risk factors, and combination of biomaterials and drug delivery systems with which to reconstruct the hierarchical periodontium.

Native vs. ribosome-crosslinked collagen membranes for periodontal regeneration: A randomized clinical trial.

AIM: To evaluate whether the ribosome-crosslinked collagen membrane (RCCM) is non-inferior to the natural collagen membrane (NCM) used in regeneration surgery in terms of clinical attachment level (CAL) gain at 6 months. METHODS: Eighty patients diagnosed as generalized periodontitis presenting with isolated infrabony defect (≥4 mm deep) were enrolled and randomized to receive regenerative surgery, either with NCM or RCCM, both combined with deproteinized bovine bone mineral (DBBM). CAL, pocket probing depth (PPD), and gingival recession (GR) were recorded at baseline, 3, and 6 months postoperatively. Periapical radiographs were taken at baseline, immediately, and 6 months after surgery. Early wound healing index (EHI) and patients' responses were recorded at 2 weeks postoperatively. RESULTS: At 6 months post-surgery, the mean CAL gain was 3.1 ± 1.5 mm in the NCM group and 2.9 ± 1.5 mm in the RCCM group, while the mean PPD was 4.3 ± 1.1 mm in the NCM group and 4.2 ± 1.0 mm in the RCCM group. Both groups demonstrated a statistically significant improvement from the baseline (p < .01). RCCM was non-inferior to NCM concerning the primary outcome (CAL gain at 6 months). The GR at 6 months postoperatively was 1.3 ± 1.2 and 1.2 ± 1.1 mm, which showed no difference compared with baseline. At 6 months follow-up, the radiographic linear bone fill (RLBF) was 6.5 ± 2.8 and 5.5 ± 2.6 mm (p > .05), while the bone fill percentage (BF%) was 102.3 ± 53.5% and 92.3 ± 40.1% (p > .05), in the NCM and RCCM groups, respectively. There was no significant difference in EHI and postoperative responses between two groups. CONCLUSION: RCCM + DBBM resulted in no-inferior clinical and radiographic outcomes to NCM + DBBM for the treatment of isolated infrabony defect in 6 months.

Comparative evaluation of the effectiveness of concentrated growth factor alone and in combination with diode laser application in the treatment of intrabony periodontal defects: A clinical and radiographic split-mouth study.

Background: Applying autologous growth factors and diode laser in periodontal therapy enhances fibroblast-mediated new attachment and osteoblastic differentiation. Hence, this study compared and evaluated the effectiveness of concentrated growth factor (CGF) alone and with diode laser application in managing intrabony periodontal defects. Methods: Ten patients with stage III periodontitis were included in this study. All the patients underwent an open flap debridement (OFD) procedure followed by CGF membrane placement in the intrabony defect in site A, whereas, in site B, after OFD, all the patients underwent diode laser irradiation before CGF membrane placement. Plaque and gingival bleeding index (PI & GBI), PPD, and clinical attachment level (CAL) were evaluated at baseline and 3 and 6 months later. Bone fill (BF), BF%, bone crest changes (BCC), and BCC% were assessed radiographically at six months postoperatively. Results: Significant reductions in PI and GBI scores, probing pocket depth (PPD), and CAL gain were observed at both sites 3 and 6 months from baseline. A significant reduction in PPD and CAL gain was noted between sites, which were higher in site B than in site A with a mean difference of 0.70±0.05 mm and 1.30±0.18 mm, 0.90±1.89 mm at 3 and 6 months, respectively. Radiographic measurement showed better BF, BF%, BCC, and BCC% at both sites at six months, which were higher at site B than at site A but statistically insignificant. Conclusion: The combination of CGF and diode laser application has demonstrated successful and promising results in terms of regeneration, improving the clinical and radiographic parameters.

The adjunctive use of antimicrobial photodynamic therapy, light-emitting-diode photobiomodulation and ozone therapy in regenerative treatment of stage III/IV grade C periodontitis: a randomized controlled clinical trial.

OBJECTIVES: To assess the short-term efficacy of multiple sessions of antimicrobial photodynamic therapy (aPDT), light-emitting-diode (LED) photobiomodulation, and topical ozone therapy applications following surgical regenerative treatments on clinical parameters, patient-centered outcomes, and mRNA expression levels of VEGF, IL-6, RunX2, Nell-1, and osterix in gingival crevicular fluid samples in patients with stage III/IV, grade C periodontitis. MATERIALS AND METHODS: Forty-eight systemically healthy patients were assigned into four groups to receive adjunctive modalities with regenerative periodontal surgical treatment. A 970 ± 15 nm diode laser plus indocyanine-green for aPDT group, a 626 nm LED for photobiomodulation group, and topical gaseous ozone were applied at 0, 1, 3, and 7 postoperative days and compared to control group. The clinical periodontal parameters, early wound healing index (EHI), and postoperative patients' morbidity were evaluated. The mRNA levels of biomarkers were assessed by real-time polymerase chain reaction. RESULTS: No significant difference in the clinical parameters except gingival recession (GR) was identified among the groups. For group-by-time interactions, plaque index (PI) and probing pocket depths (PD) showed significant differences (p = 0.034; p = 0.022). In sites with initial PD > 7 mm, significant differences were observed between control and photobiomodulation groups in PD (p = 0.011), between control and aPDT, and control and photobiomodulation groups in CAL at 6-month follow-up (p = 0.007; p = 0.022). The relative osterix mRNA levels showed a statistically significant difference among the treatment groups (p = 0.014). CONCLUSIONS: The additional applications of aPDT and LED after regenerative treatment of stage III/IV grade C periodontitis exhibited a more pronounced beneficial effect on clinical outcomes in deep periodontal pockets.

A Novel Device for the Evaluation of In Vitro Bacterial Colonization in Membranes for Guided Tissue and Bone Regeneration.

Purpose: To evaluate, in vitro, the efficiency of a novel apparatus to test the adherence and penetration of bacteria on different membranes for guided regeneration. Methodology: To create the 3D device, Computer Aided Design/Computer Aided Manufacturing (CAD/CAM) systems were used. Three types of biomaterials were tested (n = 6): (DT) a collagen membrane; (DS) a polymer membrane; and (LP) a dense polytetrafluoroethylene barrier. The biomaterials were adapted to the apparatuses and challenged with two different monospecies bacterial culture of A. actinomycetemcomitans b and S. mutans. After 2 h, bacterial adherence and penetration were quantified by counting the number of colony-forming units (CFUs). Two specimens from each group were used for image analysis using Confocal Laser Scanning Microscopy. Statistical analysis was performed. Findings: The DS group had a higher adherence of S. mutans compared to A. actinomycetemcomitans b (p = 0.05). There was less adherence of A. actinomycetemcomitans b in the DS group, compared to the LP (p = 0.011) and DT (p < 0.001) groups. Only the membranes allowed penetration, which was blocked by barriers. The DT group allowed a greater penetration of S. mutans to occur compared to A. actinomycetemcomitans b (p = 0.009), which showed a higher penetration into the DS membranes compared to S. mutans (p = 0.016). The penetration of A. actinomycetemcomitans b through DS was higher compared to its penetration through DT and LP (p < 0.01 for both). DT and DS allowed a greater penetration of S. mutans to occur compared to LP, which prevented both bacterial species from penetrating. Conclusion: The apparatus allowed for the settlement and complete sealing of the biomaterials, enabling standardization.

Comparison of immediate vs. delayed guided tissue regeneration in Infrabony defect of second molars after adjacent third molar extraction: a retrospective study.

BACKGROUND: The distal aspect of the second molar (d-M2) often exhibits infrabony defects due to the adjacent third molar. Although the defects can be treated by guided tissue regeneration (GTR) after removing the third molar, the optimal timing remains uncertain following third molar removal in clinical decision-making. This study aimed to compare delayed and immediate GTR treatments to assist in clinical decision-making. METHODS: D-M2 infrabony defects with a minimum 1-year follow-up were collected and divided into three groups: Immediate GTR group, which underwent third molar extraction and received GTR simultaneously; Delayed GTR group, which underwent delayed GTR at least 3 months after third molar extraction; and Control group, which underwent only scaling and root planing during third molar extraction. The clinical and radiographic parameters related to the infrabony defect before GTR and post-surgery were evaluated using the Kruskal-Wallis test or one-way ANOVA, followed by post-hoc Dunn's test or the Bonferroni test for pairwise comparisons. RESULTS: A total of 109 d-M2 infrabony defects were assessed. No significant differences were found between the two GTR groups, although both of them showed significant reductions in infrabony defect depth: the immediate GTR group (2.77 ± 1.97 mm vs. 0.68 ± 1.03 mm, p < 0.001) and the delayed GTR group (2.98 ± 1.08 mm vs. 0.68 ± 1.03 mm, p < 0.001) compared to the control group. CONCLUSION: GTR can effectively improve d-M2 infrabony defects when the third molar is removed, whether simultaneously or delayed. Patients may experience less discomfort with immediate GTR treatment as it requires only one surgery.

Effects of intentional early dense-polytetrafluoroethylene membrane removal on vertical ridge augmentation.

BACKGROUND: Vertical ridge augmentation (VRA) requires long healing times for bone maturation. This case study deals with the intentional early removal of a titanium-reinforced dense polytetrafluoroethylene (TR-dPTFE) membrane that allowed for treatment times reduction and improvement of bone quality. METHODS: A TR-dPTFE membrane was used for VRA in the premolar region of the upper right maxilla. The defect was filled with a mix of particulate autogenous bone and porcine xenograft in a 1:1 ratio. After a 4-month uneventful healing period, the membrane was removed, and the thick keratinized palatal tissue was moved toward the buccal side via a pedicle flap. Implants insertion and healing abutments application were carried out 3 months later, when bone graft could have been revascularized and nourished by the periosteum. RESULTS: The histologic evaluation of a bone sample harvested during implant bed preparation revealed a huge amount of mature newly formed bone even in the most coronal part. Two screw-retained crowns were delivered 2 months after implant insertion and the 3.5-year follow-up showed perfectly maintained hard and soft tissues. CONCLUSIONS: Intentional early removal of TR-dPTFE membrane after a 4-month healing time, with simultaneous soft tissue augmentation via a buccally reposioned pedicle flap, allowed graft revascularization from the periosteum, and resulted in optimal quantity and quality of the regenerated bone. This process shortened the overall treatment times, taking only 9 months from VRA to prosthetic loading. Both augmented hard and soft tissues allowed for crestal bone maintenance around implants. KEY POINTS: Titanium-reinforced dense polytetrafluoroethylene (TR-dPTFE) membranes, due to their closed structure, do not allow the passage of cells and vessels from the periosteum, and revascularization from the residual bone alone is not enough for proper graft maturation and long-term crestal bone maintenance. Early removal of TR-dPTFE membrane allows graft revascularization from the periosteum, and results in optimal quantity and quality of the regenerated bone. Increasing the thickness of the soft tissues, increasing the width of the keratinized mucosa, and repositioning the mucogingival line, via a free gingival graft or a pedicle flap, should be performed simultaneously in the membrane removal phase to reduce the number of surgical interventions, decrease patient morbidity, and shorten the total treatment time.

Long-term success and influencing factors of regenerative surgery for intra-bony defects: A retrospective cohort study.

BACKGROUND: The composite outcome measure (COM) more comprehensively assesses the clinical efficacy of regenerative surgery than a single probing measurement. We aimed to assess long-term success defined by the COM (clinical attachment level [CAL] gain of ≥3 mm and postsurgery probing pocket depth [PPD] ≤ 4 mm) and influencing factors of regenerative surgery using bone substitutes and resorbable collagen membrane (RM) for intra-bony defects (IBDs). METHODS: We retrospectively collected data from patients who underwent regenerative surgery using deproteinized bovine bone mineral (DBBM) and RM for IBDs. CAL and PPD values were compared at baseline (preoperative), 1 year (short-term), and at the last follow-up (5-10 years). Multivariate logistic regressions were performed to identify factors influencing COM-based long-term success. RESULTS: Eighty-one defects in 75 teeth of 33 patients who completed follow-up (6.5 ± 1.4 years) were included. One tooth was lost. All defects with complete follow-up exhibited long-term average CAL gain (3.00 ± 2.00 mm, 95% confidence interval [CI]: 2.56-3.44 mm, p < 0.001) and PPD reduction (2.06 ± 1.91 mm, 95% CI: 1.64-2.49 mm, p < 0.001). Long-term success was achieved in 38.8% of IBDs. CAL and PPD values were comparable between 1 year and the last follow-up. Logistic regression analyses revealed that male sex (odds ratio [OR] = 0.23, 95% CI: 0.07-0.75) and bleeding on probing (BOP) during supportive periodontal therapy (OR = 0.96, 95% CI: 0.94-0.99) were risk factors for long-term success. CONCLUSIONS: Regenerative surgery with DBBM and RM for IBDs can achieve some degree of long-term success defined by COM. However, within this study's limitations, male sex and higher BOP incidence postoperatively are negatively associated with optimal long-term success. CLINICAL TRIAL NUMBER: ChiCTR2300069016.

Effectiveness of leukocyte- and platelet-rich fibrin in the management of medication-related osteonecrosis of the jaws ­ a systematic review / Efectividad de la fibrina rica en leucocitos y plaquetas en el tratamiento de osteonecrosis mandibular relacionada con medicamentos: una revisión sistemática

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but significant adverse event primarily associated with the intake of antiresorptive and antiangiogenic medications. Although antiresorptive and antiangiogenic the-rapies improve life expectancy, particularly in cancer patients, MRONJ may hamper the patient's quality of life due to pain, discomfort, anxiety, depression, speech impairment, difficulty in swallowing and eating, frequent medical and dental evaluations and treatments, and the possibility of treatment discontinuation. Leukocyte­ and Platelet-rich Fibrin (L-PRF) is an autologous platelet aggregate that promotes wound healing by stimulating re-epithelialization, angiogenesis, and extracellular matrix production. Aim: The present systematic review aimed to compare the results in the published literature on whether L-PRF is an effective and predictable adjuvant to surgical debridement of necrotic bone for improving the healing efficacy in patients with MRONJ. Materials and Methods: The PubMed, Scopus, Cochrane, Science Direct, LILACS, and Web of Science databases were searched using the predetermined MeSH terms and eligibility criteria, and the search yielded a total of five articles. Two studies were retrospective, and three studies were case series. Results: Seventeen participants received a combination of surgical debridement, L-PRF membrane, and antibiotics. Complete wound healing was observed in 70% of the participants, and most of them healed without any complications. Conclusions: L-PRF as an adjuvant to surgical debridement of necrosed bone appears to have a positive association with the healing outcome in patients with MRONJ.

Introducción: La osteonecrosis mandibular relacionada con medicamentos (ONMRM) es un evento adverso raro pero significativo asociado principalmente con la ingesta de medicamentos antirresortivos y antiangiogénicos. Aunque las terapias antirresortivas y antiangiogénicas mejoran la esperanza de vida, particularmente en pacientes con cáncer, la ONMRM puede obstaculizar la calidad de vida del paciente debido a dolor, incomodidad, ansiedad, depresión, discapacidad del habla, dificultad para tragar y comer, evaluaciones y tratamientos médicos y dentales frecuentes, y la posibilidad de interrupción del tratamiento. La fibrina rica en plaquetas y leucocitos (L-PRF) es un agregado de plaquetas autólogo que promueve la curación de heridas al estimular la reepitelización, la angiogénesis y la producción de la matriz extracelular. Objetivo: La presente revisión sistemática tuvo como objetivo comparar los resultados en la literatura publicada sobre si L-PRF es un adyuvante efectivo y predecible al desbridamiento quirúrgico del hueso necrótico para mejorar la eficacia curativa en pacientes con ONMRM. Materiales y Métodos: Las bases de datos de PubMed, Scopus, Cochrane, ScienceDirect, LILACS y Web of Science se registraron utilizando los términos DeCS/MeSH predeterminados y los criterios de elegibilidad, y la búsqueda arrojó un total de cinco artículos. Dos estudios fueron retrospectivos, y tres estudios fueron series de casos. Resultado: Diecisiete participantes recibieron una combinación de desbridamiento quirúrgico, membrana L-PRF y antibióticos. Se observó curación completa de heridas en el 70% de los participantes, y la mayoría de ellos se curaron sin ninguna complicación. Conclusión: L-PRF como adyuvante para el desbridamiento quirúrgico del hueso necrótico parece tener una asociación positiva con el resultado de curación en pacientes con ONMRM.

Instructions for the use of L-PRF in different clinical indications.

Autologous platelet concentrates (APCs) have demonstrated clear benefits across various clinical applications, including alveolar ridge preservation, guided tissue regeneration, guided bone regeneration, sinus floor elevation (both lateral window approach and transcrestal technique), endodontic surgery, the treatment of medication-related osteonecrosis of the jaw bones, and periodontal plastic surgery. To ensure an optimal clinical outcome, clinicians must adhere strictly to the protocol to prepare the APCs and, especially follow evidence-based surgical guidelines, often simple but crucial, to minimize the likelihood of errors. The majority of clinical trials reported on second-generation APCs [the leukocyte- and platelet-rich fibrin (L-PRF) family, including its modifications (A-PRF, A-PRF+, CGF, T-PRF, H-PRF, etc.)]. These second-generation APCs offer additional benefits compared to the first-generation APCs, making them the preferred choice for the development of clinical recommendations. These recommendations have been formulated through a meticulous examination of the available clinical data and the clinical experience of the authors of this paper.