Infection-Sensitive SPION/PLGA Scaffolds Promote Periodontal Regeneration via Antibacterial Activity and Macrophage-Phenotype Modulation.

Inflammation caused by a bacterial infection and the subsequent dysregulation of the host immune-inflammatory response are detrimental to periodontal regeneration. Herein, we present an infection-sensitive scaffold prepared by layer-by-layer assembly of Feraheme-like superparamagnetic iron oxide nanoparticles (SPIONs) on the surface of a three-dimensional-printed polylactic-co-glycolic acid (PLGA) scaffold. The SPION/PLGA scaffold is magnetic, hydrophilic, and bacterial-adhesion resistant. As indicated by gene expression profiling and confirmed by quantitative real-time reverse transcription polymerase chain reaction and flow cytometry analysis, the SPION/PLGA scaffold facilitates macrophage polarization toward the regenerative M2 phenotype by upregulating IL-10, which is the molecular target of repair promotion, and inhibits macrophage polarization toward the proinflammatory M1 phenotype by downregulating NLRP3, which is the molecular target of anti-inflammation. As a result, macrophages modulated by the SPS promote osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) in vitro. In a rat periodontal defect model, the SPION/PLGA scaffold increased IL-10 secretion and decreased NLRP3 and IL-1ß secretion with Porphyromonas gingivalis infection, achieving superior periodontal regeneration than the PLGA scaffold alone. Therefore, this antibacterial SPION/PLGA scaffold has anti-inflammatory and bacterial antiadhesion properties to fight infection and promote periodontal regeneration by immunomodulation. These findings provide an important strategy for developing engineered scaffolds to treat periodontal defects.

Advances in biomaterials for oral-maxillofacial bone regeneration: spotlight on periodontal and alveolar bone strategies.

The intricate nature of oral-maxillofacial structure and function, coupled with the dynamic oral bacterial environment, presents formidable obstacles in addressing the repair and regeneration of oral-maxillofacial bone defects. Numerous characteristics should be noticed in oral-maxillofacial bone repair, such as irregular morphology of bone defects, homeostasis between hosts and microorganisms in the oral cavity and complex periodontal structures that facilitate epithelial ingrowth. Therefore, oral-maxillofacial bone repair necessitates restoration materials that adhere to stringent and specific demands. This review starts with exploring these particular requirements by introducing the particular characteristics of oral-maxillofacial bones and then summarizes the classifications of current bone repair materials in respect of composition and structure. Additionally, we discuss the modifications in current bone repair materials including improving mechanical properties, optimizing surface topography and pore structure and adding bioactive components such as elements, compounds, cells and their derivatives. Ultimately, we organize a range of potential optimization strategies and future perspectives for enhancing oral-maxillofacial bone repair materials, including physical environment manipulation, oral microbial homeostasis modulation, osteo-immune regulation, smart stimuli-responsive strategies and multifaceted approach for poly-pathic treatment, in the hope of providing some insights for researchers in this field. In summary, this review analyzes the complex demands of oral-maxillofacial bone repair, especially for periodontal and alveolar bone, concludes multifaceted strategies for corresponding biomaterials and aims to inspire future research in the pursuit of more effective treatment outcomes.

Staged Regenerative-Phenotype Modification Therapy for Multiple RT3 Gingival Recessions in Periodontally Compromised Anterior Mandibular Teeth: A Case Report.

We report the successful treatment of multiple recession type (RT) 3 gingival recessions in periodontally compromised mandibular anterior teeth with limited keratinized tissue. A 35-yearold man with stage III, grade C periodontitis underwent a two-stage intervention. Initially, a modification of the connective tissue graft (m-CTG) wall technique was used as part of phenotype modification therapy. The CTG acted as a protective 'wall,' securing space for periodontal regeneration, enhancing root coverage, soft tissue thickness, and keratinized mucosal width. Recombinant human fibroblast growth factor-2 and carbonate apatite promoted periodontal regeneration. This procedure successfully facilitated periodontal regeneration, resulting in the transition from RT3 to RT2 gingival recession and adequate keratinized mucosal width. Eighteen months later, the second surgery used a tunneled coronally advanced flap (TCAF) for root coverage. TCAF involved combining a coronally advanced flap and tunnel technique by elevating the trapezoidal surgical papilla and using a de-epithelialized CTG inserted beneath the tunneled flap. Root conditioning with ethylenediaminetetraacetic acid and enamel matrix derivative gel application were performed. Consequently, mean CAL gain was 5.3 mm, mean root coverage was 4.5 mm in height, and the gingival phenotype improved at the treated sites by the 12-month follow-up. This staged approach addresses the challenges of treating RT3 gingival recession with promising outcomes.

ECM-Mimicking Strontium-Doped Nanofibrous Microspheres for Periodontal Tissue Regeneration in Osteoporosis.

Regenerating periodontal defects in osteoporosis patients presents a significant clinical challenge. Unlike the relatively straightforward regeneration of homogeneous bone tissue, periodontal regeneration requires the intricate reconstruction of the cementum-periodontal ligament-alveolar bone interface. Strontium (Sr)-doped biomaterials have been extensively utilized in bone tissue engineering due to their remarkable pro-osteogenic attributes. However, their application in periodontal tissue regeneration has been scarcely explored. In this study, we synthesized an innovative injectable Sr-BGN/GNM scaffold by integrating Sr-doped bioactive glass nanospheres (Sr-BGNs) into the nanofiber architecture of gelatin nanofiber microspheres (GNMs). This design, mimicking the natural bone extracellular matrix (ECM), enhanced the scaffold's mechanical properties and effectively controlled the sustained release of Sr ions (Sr2+), thereby promoting the proliferation, osteogenic differentiation, and ECM secretion of PDLSCs and BMSCs, as well as enhancing vascularization in endothelial cells. In vivo experiments further indicated that the Sr-BGNs/GNMs significantly promoted osteogenesis and angiogenesis. Moreover, the scaffold's tunable degradation kinetics optimized the prolonged release and pro-regenerative effects of Sr2+ in vivo, matching the pace of periodontal regeneration and thereby facilitating the regeneration of functional periodontal tissues under osteoporotic conditions. Therefore, Sr-BGNs/GNMs emerge as a promising candidate for advancing periodontal regeneration strategies.

Clinical and Radiographic Evaluation of Intrabony Periodontal Defects Treated with Hyaluronic Acid or Enamel Matrix Proteins: A 6-Month Prospective Study.

PURPOSE: To compare the regenerative clinical and radiographic effects of cross-linked hyaluronic acid (xHyA) with enamel matrix proteins (EMD) at six months after regenerative treatment of periodontal intrabony defects. MATERIALS AND METHODS: Sixty patients presenting one intrabony defect each were randomly assigned into control (EMD) and test (xHyA) groups. Clinical attachment level (CAL) gain was the primary outcome, while pocket probing depth (PPD), gingival recession (REC), bleeding on probing (BOP), full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), and radiographic parameters such as defect depth (BC-BD), and defect width (DW) were considered secondary outcome variables. Parameters were recorded at baseline and after 6 months. RESULTS: At the 6-month follow-up, 54 patients were available for statistical analysis. In the control and test groups, the mean CAL gain was statistically significant in the intragroup comparison (p < 0.001). 48.1% of test sites showed a CAL gain ≤ 2 mm compared with 33.3% of control sites. The mean PPD reduction was statistically significant in the intragroup comparison in both groups (p < 0.001). The mean REC increase was similar in the two groups: 1.04 ± 1.29 mm vs 1.11 ± 1.22 mm (test vs control). The mean BC-BD, DW, FMPS, FMBS, and BOP changed statistically significantly only in the intragroup comparison, not in the intergroup comparison. CONCLUSION: Both treatments, EMD and xHyA, produced similar statistically significant clinical and radiographical improvements after six months when compared with baseline.

Temporal and spatial expression analysis of periostin in mice periodontitis model.

OBJECTIVES: This study aimed to investigate the temporal and spatial changes in the expression of periostin during periodontal inflammation in mice. METHODS: A periodontitis model was constructed using silk thread ligation. Mice were randomly divided into five groups including control group, 4-day ligation group, 7-day ligation group, 14-day ligation group, and self-healing group (thread removal for 14 days after 14-day ligation). Micro-CT and histological staining were performed to characterize the dynamic changes in the mouse periodontal tissue in each group. RNAscope and immunohistochemical staining were used to analyze the pattern of changes in periostin at various stages of periodontitis. The cell experiment was divided into three groups: control group, lipopolysaccharide (LPS) stimulation group (treated with LPS for 12 h), and LPS stimulation removal group (treated with LPS for 3 h followed by incubation with medium for 9 h). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of periostin, transforming growth factor-ß1 (TGF-ß1), and matrix metalloproteinase 2 (MMP2). RESULTS: Significant alveolar bone resorption was observed 7 days after ligation. With increasing duration of ligation, the damage to the mouse periodontal tissue was aggravated, which manifested as increased osteoclasts, widening of the periodontal membrane space, and decreased alveolar bone height. Some degree of periodontal tissue repair was observed in the self-healing group. Periostin expression decreased at 4 and 7 days compared with the control group and increased at 14 days compared with 4 and 7 days. A significant recovery was found in the self-healing group. The qRT-PCR results showed that the expression of periostin and TGF-ß1 in the LPS stimulation group decreased compared with that in the control group but significantly recovered in the LPS removal group. CONCLUSIONS: Periostin expression in the PDL of mice showed a downward and upward trend with inflammation progression. The significant recovery of periostin expression after removing inflammatory stimuli may be related to TGF-ß1, which is crucial to maintain the integrity of the PDL.

Intentional Replantation in Combination with Fibroblast Growth Factor-2 Application and Orthodontic Tooth Extrusion for Periodontal Regeneration in the Treatment of Severe Endodontic-Periodontal Lesions.

Endodontic-periodontal lesions are characterized by the involvement of the pulp and periodontal disease in the same tooth. Despite successful root canal treatment, if the majority of bone support has been lost from periodontitis, the tooth may have a poor prognosis. In severe endodontic-periodontal lesions, the periodontal tissue regenerates poorly because of the significant loss of the periodontal ligament and cementum, poor tooth stability, and bone defect morphology unfavorable for bone regeneration. To overcome these difficult situations, in this case, osteotomy of the replantation bed and tooth replantation with horizontal rotation and deep placement were performed. To improve periodontal regeneration, fibroblast growth factor (FGF) 2 was applied to the artificially made periodontal defect. In addition, orthodontic extrusion of the deeply replaced tooth was performed for potential coronal migration of the periodontal tissue. This case presents a unique multidisciplinary method of treating severe endodontic-periodontal lesions using intentional replantation combined with FGF 2 application and orthodontic extrusion.

A Comparative Evaluation of Advanced Platelet-Rich Fibrin Combined With Demineralized Freeze-Dried Bone Allograft and Demineralized Freeze-Dried Bone Allograft Alone in the Treatment of Periodontal Infrabony Defects: A Clinical and Radiographic Study.

Aim Allografts, autografts, alloplast and xenografts are frequently used for periodontal regeneration. The aim of this study was to determine the efficacy of advanced platelet-rich fibrin (A-PRF) in combination with demineralized freeze-dried bone allograft (DFDBA) and DFDBA alone in periodontal infrabony defects. Methodology This was a split-mouth design study where 20 infrabony defects in 10 patients were included. Patients were randomly divided into two groups, where DFDBA allograft and A-PRF were used in the test group, while the DFDBA allograft alone was used in the control group. Furthermore, the results were evaluated at baseline, three, and nine months, respectively, in terms of clinical and radiographic parameters. Data were analysed with an unpaired t-test at the significance level of P < 0.05 (statistically significant). Results Both treatments showed reduced clinical and radiographic parameters from baseline to nine months. There was a non-significant difference in the plaque index (PI), bleeding on probing (BOP), clinical attachment level (CAL), and radiographic defect fill (RDF). In comparison to the control group (3.40 ± 0.516), the probing pocket depth (PPD) in the test group at nine months (3.22 ± 0.422) was statistically significant showing reduction in the PPD (P = 0.042). Conclusion Within its limitations, the study showed that A-PRF plus DFDBA and DFDBA alone treatment modalities reduced clinical and radiographic parameters from baseline, at 9 months; however, the inclusion of A-PRF did not substantially improve the treatment outcome when comparing both the groups, except for the probing pocket depth after nine months.

The flapless approach with and without enamel matrix derivatives for the treatment of intrabony defects: A randomized controlled clinical trial.

AIM: To compare the clinical and radiographic outcomes of flapless procedure alone or in combination with enamel matrix derivatives (EMD) in the treatment of deep intrabony defects. MATERIALS AND METHODS: Forty-six patients re-evaluated after non-surgical therapy were randomly assigned to the test (flapless with EMD) or control group (flapless alone). Clinical measurements were recorded pre-surgery and at 6 and 12 months after surgery, and radiographic measurements were taken pre-surgery and after 12 months. RESULTS: Forty-six patients completed the study. Improvements were observed in both groups at 12 months for mean clinical attachment level (CAL) gain, with significant differences between test (3.9 ± 1.1 mm) and control groups (3.0 ± 1.2) (p = .017). Probing pocket depth (PPD) reduction (4.0 ± 0.7 vs. 3.3 ± 1.4 mm) was also near to statistical significance (p = .051). Also, more sites achieved successful composite outcome measure (final PPD ≤ 4 mm and CAL gain ≥3 mm) for the regenerative treatment in the flapless + EMD group (82.6% vs. 52.2%; p = .028). In terms of radiographic outcomes, EMD yielded a greater defect bone fill than flapless treatment alone (3.0 ± 1.0 mm vs. 1.8 ± 1.5 mm; p < .001). CONCLUSIONS: The additional application of EMD during the flapless procedure for intrabony defects slightly improved clinical and radiographic outcomes. CLINICALTRIALS: gov identification number: NCT05456555.

Inflammatory and bone remodelling related biomarkers following periodontal transplantation of the tissue engineered biocomplex.

OBJECTIVES: To assess gingival crevicular fluid (GCF) levels of inflammatory and bone remodelling related biomarkers following transplantation of a tissue-engineered biocomplex into intrabony defects at several time-points over 12-months. MATERIALS AND METHODS: Group-A (n = 9) received the Minimal Access Flap (MAF) surgical technique combined with a biocomplex of autologous clinical-grade alveolar bone-marrow mesenchymal stem cells in collagen scaffolds enriched with an autologous fibrin/platelet lysate (aFPL). Group-B (n = 10) received the MAF surgery, with collagen scaffolds enriched with aFPL and Group-C (n = 8) received the MAF surgery alone. GCF was collected from the osseous defects of subjects via paper strips/30 sec at baseline, 6-weeks, 3-, 6-, 9-, 12-months post-surgery. Levels of inflammatory and bone remodelling-related biomarkers in GCF were determined by ELISA. RESULTS: Group-A demonstrated significantly higher GCF levels of BMP-7 at 6-9 months than baseline, with gradually decreasing levels of pro-inflammatory and pro-osteoclastogenic markers (TNF-α, RANKL) over the study-period; and an overall decrease in the RANKL/OPG ratio at 9-12 months than baseline (all p < 0.001). In comparison, only modest interim changes were observed in Groups-B and -C. CONCLUSIONS: At the protein level, the approach of MAF and biocomplex transplantation provided greater tissue regeneration potential as cell-based therapy appeared to modulate inflammation and bone remodelling in residual periodontal defects. CLINICAL RELEVANCE: Transplantation of a tissue engineered construct into periodontal intrabony defects demonstrated a biochemical pattern for inflammatory control and tissue regeneration over 12-months compared to the control treatments. Understanding the biological healing events of stem cell transplantation may facilitate the design of novel treatment strategies. CLINICAL DATABASE REGISTRATION: ClinicalTrials.gov ID: NCT02449005.

Hydrogels promote periodontal regeneration.

Periodontal defects involve the damage and loss of periodontal tissue, primarily caused by periodontitis. This inflammatory disease, resulting from various factors, can lead to irreversible harm to the tissues supporting the teeth if not treated effectively, potentially resulting in tooth loss or loosening. Such outcomes significantly impact a patient's facial appearance and their ability to eat and speak. Current clinical treatments for periodontitis, including surgery, root planing, and various types of curettage, as well as local antibiotic injections, aim to mitigate symptoms and halt disease progression. However, these methods fall short of fully restoring the original structure and functionality of the affected tissue, due to the complex and deep structure of periodontal pockets and the intricate nature of the supporting tissue. To overcome these limitations, numerous biomaterials have been explored for periodontal tissue regeneration, with hydrogels being particularly noteworthy. Hydrogels are favored in research for their exceptional absorption capacity, biodegradability, and tunable mechanical properties. They have shown promise as barrier membranes, scaffolds, carriers for cell transplantation and drug delivery systems in periodontal regeneration therapy. The review concludes by discussing the ongoing challenges and future prospects for hydrogel applications in periodontal treatment.

Evaluation of Clinical Efficacy of 1.2% Rosuvastatin Hydrogel as an Adjunct to Scaling and Root Planing in Generalized Chronic Periodontitis.

Background Periodontitis, characterized by chronic inflammation and tissue destruction, remains a significant public health concern. Conventional treatment like scaling and root planing (SRP) is effective but often augmented with adjunctive therapies to improve outcomes. Local drug delivery (LDD) systems containing pharmacological agents offer targeted treatment with reduced systemic side effects. Rosuvastatin (RSV), known for its anti-inflammatory and tissue regenerative properties, has shown promise in periodontal therapy. This prospective clinical trial assessed the effectiveness of 1.2% RSV hydrogel as an adjunct to SRP in managing generalized chronic periodontitis. Methods Thirty patients were grouped into Group A (SRP alone) and Group B (SRP + 1.2% RSV hydrogel). Clinical measurements, such as the modified sulcular bleeding index (mSBI), probing pocket depth (PPD), and clinical attachment level (CAL), were documented both at the beginning of the study and after three months. Statistical analysis was performed using SPSS software. A p-value of less than 0.05 was considered statistically significant. Results Participants in Group B showed significant improvements in mSBI (from 2.34 ± 0.59 to 1.01 ± 0.29), PPD (from 7.36 ± 1.12 mm to 4.63 ± 0.88 mm), and CAL (from 8.56 ± 1.22 mm to 5.90 ± 1.24 mm) compared to Group A at the three-month follow-up. The mean values of these parameters decreased significantly in both groups from baseline to three months. However, the reductions were more substantial in Group B, indicating the beneficial effect of RSV hydrogel adjunctive therapy. Conclusion The study demonstrates the efficacy of 1.2% RSV hydrogel employed as a localized drug in enhancing the outcomes of SRP for generalized chronic periodontitis. The adjunctive use of RSV hydrogel led to noteworthy enhancements in clinical parameters, highlighting its potential in periodontal therapy.

Multifunctional bilayer nanofibrous membrane enhances periodontal regeneration via mesenchymal stem cell recruitment and macrophage polarization.

The continuous stimulation of periodontitis leads to a decrease in the number of stem cells within the lesion area and significantly impairing their regenerative capacity. Therefore, it is crucial to promote stem cell homing and regulate the local immune microenvironment to suppress inflammation for the regeneration of periodontitis-related tissue defects. Here, we fabricated a novel multifunctional bilayer nanofibrous membrane using electrospinning technology. The dense poly(caprolactone) (PCL) nanofibers served as the barrier layer to resist epithelial invasion, while the polyvinyl alcohol/chitooligosaccharides (PVA/COS) composite nanofiber membrane loaded with calcium beta-hydroxy-beta-methylbutyrate (HMB-Ca) acted as the functional layer. Material characterization tests revealed that the bilayer nanofibrous membrane presented desirable mechanical strength, stability, and excellent cytocompatibility. In vitro, PCL@PVA/COS/HMB-Ca (P@PCH) can not only directly promote rBMSCs migration and differentiation, but also induce macrophage toward pro-healing (M2) phenotype-polarization with increasing the secretion of anti-inflammatory and pro-healing cytokines, thus providing a favorable osteoimmune environment for stem cells recruitment and osteogenic differentiation. In vivo, the P@PCH membrane effectively recruited host MSCs to the defect area, alleviated inflammatory infiltration, and accelerated bone defects repair. Collectively, our data indicated that the P@PCH nanocomposite membrane might be a promising biomaterial candidate for guided tissue regeneration in periodontal applications.

Impact of Inflammatory Markers and Senescence-Associated Secretory Phenotype in the Gingival Crevicular Fluid on the Outcomes of Periodontal Regeneration.

The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP [interleukin (IL)-1ß, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9]. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year [COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm]. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1ß and MMP-8 and -9 (p < 0.001), while IL-12 showed a direct relationship with CAL gain (p = 0.005) and PPD reduction (p = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes.

Insights and Advancements in Periodontal Tissue Engineering and Bone Regeneration.

The regeneration of periodontal bone defects continues to be an essential therapeutic concern in dental biomaterials. Numerous biomaterials have been utilized in this sector so far. However, the immune response and vascularity in defect regions may be disregarded when evaluating the effectiveness of biomaterials for bone repair. Among several regenerative treatments, the most recent technique of in situ tissue engineering stands out for its ability to replicate endogenous restorative processes by combining scaffold with particular growth factors. Regenerative medicine solutions that combine biomaterials/scaffolds, cells, and bioactive substances have attracted significant interest, particularly for bone repair and regeneration. Dental stem cells (DSCs) share the same progenitor and immunomodulatory properties as other types of MSCs, and because they are easily isolable, they are regarded as desirable therapeutic agents in regenerative dentistry. Recent research has demonstrated that DSCs sown on newly designed synthetic bio-material scaffolds preserve their proliferative capacity while exhibiting increased differentiation and immuno-suppressive capabilities. As researchers discovered how short peptide sequences modify the adhesion and proliferative capacities of scaffolds by activating or inhibiting conventional osteogenic pathways, the scaffolds became more effective at priming MSCs. In this review, the many components of tissue engineering applied to bone engineering will be examined, and the impact of biomaterials on periodontal regeneration and bone cellular biology/molecular genetics will be addressed and updated.

Healing of Periodontal Suprabony Defects following Treatment with Open Flap Debridement with or without Hyaluronic Acid (HA) Application.

Background and Objectives: This randomized, double-arm, multicentric clinical trial aims to compare the clinical outcomes following the treatment of suprabony periodontal defects using open flap debridement (OFD) with or without the application of hyaluronic acid (HA). Materials and Methods: Sixty systemically healthy patients with at least two teeth presenting suprabony periodontal defects were randomly assigned with a 1:1 allocation ratio using computer-generated tables into a test (OFD + HA) or control group (OFD). The main outcome variable was clinical attachment level (CAL). The secondary outcome variables were changes in mean probing pocket depth (PPD), gingival recession (GR), full-mouth plaque score (FMPS), and full-mouth bleeding score (FMBS). All clinical measurements were carried out at baseline and 12 months. Results: Sixty patients, thirty in each group, were available for statistical analysis. The mean CAL gain was statistically significantly different (p < 0.001) in the test group compared with the control group (3.06 ± 1.13 mm vs. 1.44 ± 1.07 mm). PPD reduction of test group measurements (3.28 ± 1.14 mm) versus the control group measurements (2.61 ± 1.22 mm) were statistically significant (p = 0.032). GR changes were statistically significant only in the test group 0.74 ± 1.03 mm (p < 0.001). FMBS and FMPS revealed a statistically significant improvement mostly in the test group. Conclusions: Suprabony periodontal defects could benefit from the additional application of HA in conjunction with OFD in terms of improvement of the clinical parameters compared with OFD alone.

Orally Derived Stem Cell-Based Therapy in Periodontal Regeneration: A Systematic Review and Meta-Analysis of Randomized Clinical Studies.

The present systematic review was performed to assess the application of orally derived stem cells in periodontal regenerative therapy, and because of this, the following PICO question was proposed: "In patients with periodontitis, can the adjunctive use of orally derived stem cells provide additional clinical and radiographic benefits for periodontal regeneration?". Randomized clinical studies were electronically and manually searched up until December 2023. Quantitative analyses were performed with the aim of evaluating the mean differences (MDs) between the treatment and control groups in terms of clinical attachment level (CAL) gain, probing pocket depth (PPD) reduction, gingival recession (GR), and radiographic bone gain (RBG) using random effect models. A total of seven studies were selected for the systematic review. Meta-analyses excluding studies with a high risk of bias highlighted a non-statistically significant result for the use of stem cells when compared to the control groups in terms of CAL gain [MD = 1.05; 95% CI (-0.88, 2.97) p = 0.29] and PPD reduction [MD = 1.32; 95% CI (-0.25, 2.88) p = 0.10]. The same also applied to GR [MD = -0.08; 95% CI (-0.79, 0.63) p = 0.83] and RBG [MD = 0.50; 95% CI (-0.88, 1.88) p = 0.48]. Based on the high heterogeneity, there is not enough evidence to consider the adjunctive application of orally derived mesenchymal stem cells as a preferential approach for periodontal regenerative treatment, as compared to standard procedures.

Optimizing esthetic zone periodontal regeneration in a 1-2-wall infrabony defect using recombinant human platelet-derived growth factor BB and ß-tricalcium phosphate: A case report.

OBJECTIVE: Periodontitis is an inflammatory condition induced by subgingival bacterial dysbiosis, resulting in inflammatory-mediated destruction of tooth-supporting structures, potentially leading to the formation of infrabony defects. This case report describes the treatment of a patient who presented with a combination 1-2-wall defect on tooth 21. To maintain the residual periodontal attachment and minimize esthetic consequences, a regenerative approach was performed using recombinant human platelet-derived growth factor-BB (rh-PDGF-BB) and ß-tricalcium phosphate (ß-TCP). MATERIALS AND METHODS: At the time of postscaling/root planing reevaluation, a 34-year-old Asian male initially diagnosed with molar/incisor pattern stage III grade C periodontitis exhibited a 6-mm residual probing depth on the mesiopalatal aspect of tooth 21. Periodontal regenerative surgery was performed using rh-PDGF-BB with ß-TCP, without the use of a membrane. RESULTS: At the 1-year follow-up, a significant reduction in probing depth and radiographic evidence of bone fill were observed. Additionally, re-entry surgery for implant placement at site tooth 23 confirmed bone fill in the defect on tooth 21. CONCLUSION: These results demonstrate the efficacy of rh-PDGF-BB with ß-TCP in enhancing periodontal regeneration and support its use as a treatment option when treating poorly contained infrabony defects in the esthetic zone.

Melt electrowriting scaffolds with fibre-guiding features for periodontal attachment.

Periodontal regeneration requires the re-attachment of oblique and perpendicular periodontal ligament (PDL) fibres to newly formed cementum and alveolar bone, which has proven elusive with existing approaches. In this study, multiple fibre-guiding biphasic tissue engineered constructs were fabricated by melt electrowriting. The biphasic scaffolds were 95 % porous and consisted of a pore size gradient bone compartment and periodontal compartment made of fibre-guiding channels with micro-architectural features ranging from 100 to 60 µm aimed to direct PDL fibre alignment and attachment. In vitro evaluations over 3 and 7 days demonstrated a marked improvement in collagen fibre orientation (over 60 % fully aligned) for scaffolds with micro-architecture ≤100 µm. The biphasic scaffolds were placed on a dentine slice and implanted ectopically, and this demonstrated that all micro-channels groups facilitated oblique and perpendicular alignment and attachment on the dentine with a mean nuclei angle and mean collagen fibre angle of approximately 60° resembling the native periodontal ligament attachment. A further in vivo testing using a surgically created rodent periodontal model highlighted the 80 µm micro-channel group's effectiveness, showing a significant increase in oblique PDL fibre attachment (72 %) and periodontal regeneration (56 %) when compared to all other groups onto the tooth root compared to control groups. Further to this, immunohistochemistry demonstrated the presence of periostin in the newly formed ligament indicating that functional regeneration occurred These findings suggest that scaffold micro-architectures of 100 µm or below can play a crucial role in directing periodontal tissue regeneration, potentially addressing a critical gap in periodontal therapy. STATEMENT OF SIGNIFICANCE: Periodontal regeneration remains a significant clinical challenge. Essential to restoring dental health and function is the proper attachment of the periodontal ligament, which is functionally oriented, to regenerated bone and cementum. Our research presents an innovative biphasic scaffold, utilizing Melt Electrowriting to systematically guide tissue growth. Distinct from existing methods, our scaffold is highly porous, adaptable, and precisely guides periodontal ligament fibre attachment to the opposing tooth root and alveolar bone interfaces, a critical step for achieving periodontal functional regeneration. Our findings not only bridge a significant gap in biomaterial driven tissue guidance but also promise more predictable outcomes for patients, marking a transformative advancement in the field.

Advances in Hydrogels for Periodontitis Treatment.

Periodontitis is a common condition characterized by a bacterial infection and the disruption of the body's immune-inflammatory response, which causes damage to the teeth and supporting tissues and eventually results in tooth loss. Current therapy involves the systemic and local administration of antibiotics. However, the existing treatments cannot exert effective, sustained release and maintain an effective therapeutic concentration of the drug at the lesion site. Hydrogels are used to treat periodontitis due to their low cytotoxicity, exceptional water retention capability, and controlled drug release profile. Hydrogels can imitate the extracellular matrix of periodontal cells while offering suitable sites to load antibiotics. This article reviews the utilization of hydrogels for periodontitis therapy based on the pathogenesis and clinical manifestations of the disease. Additionally, the latest therapeutic strategies for smart hydrogels and the main techniques for hydrogel preparation have been discussed. The information will aid in designing and preparing future hydrogels for periodontitis treatment.