[Clinical effect of MB-PDT assisted initial therapy on alveolar angle absorption of lower anterior teeth].

PURPOSE: To evaluate the effect of MB-PDT assisted essential therapy on angle resorption of lower anterior alveolar bone in patients with periodontitis. METHODS: Forty patients who were diagnosed with periodontitis stage III-IV or C, lower anterior teeth alveolar bone angle resorption, and periodontal pocket depth greater than 4 mm were selected from April 2018 to October 2020 in the Department of Periodontology and Oral Mucosal Diseases, Changsha Stomatological Hospital. The patients were randomly divided into control group and experimental group with 20 cases in each group. Compared with the control group which was only managed with essential treatment, the experimental group was treated with MB-PDT on the basis of the control group. The plaque index (PLI) and gingival bleeding index (GBI) scores of the two groups were recorded before surgery and 1 and 2 weeks after surgery. Probing depth (PD) and clinical attachment level (CAL) were detected before and 6 months after surgery. Statistical analysis of the data was performed using Graphpad Prism 5 software package. RESULTS: The PLI and GBI of the experimental group were significantly lower than those of the control group at 1 and 2 weeks after operation(P＜0.05). Six months after surgery, PD and CAL levels in the experimental group were significantly lower than those in the control group (P＜0.05). CONCLUSIONS: MB-PDT adjuvant therapy has the advantages of simple operation, efficient sterilization, promotion of healing, and high safety performance. It may be a new non-surgical adjuvant treatment strategy for effective treatment of lower anterior alveolar angular resorption.

Platelet Rich Fibrin Matrix (PRFM) and Peripheral Blood Mesenchymal Stem Cells (PBMSCs) in the management of intraosseous defects - A randomized clinical trial.

OBJECTIVE: A combination of peripheral blood mesenchymal stem cells (PBMSCs) and platelet rich fibrin matrix (PRFM) could be a probable periodontal regenerative material with the synergy of the added benefits of each material. This randomized controlled clinical trial aimed to evaluate the regenerative capacity of supercell (PRFM and PBMSCs) compared with that of PRFM alone in human periodontal mandibular intraosseous defects (IOD). METHODOLOGY: This study included 17 patients of both sexes (12 men, 5 women) aged 30-55 years (mean age = 37.7±4.4 years) who fulfilled the inclusion criteria (radiographic and clinical evaluation for bilateral IOD with probing pocket depth (PPD ≥ 6 mm). A split-mouth design was used in each patient. A total of 34 sites in the mandibular arch randomly received PRFM alone + open flap debridement (OFD) [Control sites] or supercell (PRFM+PBMSCs) + OFD [Test sites]. The clinical parameters plaque index (PI), gingival index (GI), PPD, clinical attachment level (CAL), and in the radiographic parameters; defect depth (DD) and defect fill percentage (DFP) were recorded at baseline, 3 and 6 months postoperatively. Early wound healing index (EHI) was used at 1 week to assess wound healing ability. RESULTS: At 6 months, radiographic parameters revealed significant reduction in DD (P<0.001) and significant DFP values in the test group compared with the control group. The supercell showed significant improvement in PPD and CAL at the end of 6 months (P<0.001). EHI scores at 1 week showed no statistically significant difference between the test and control groups. CONCLUSION: Supercell can be considered a regenerative material in the treatment of periodontal IODs.

Comparative study of demineralized freeze-dried bone allograft and its combination with platelet-rich fibrin in the treatment of intrabony defects: A randomized clinical trial.

BACKGROUND: The clinical and radiographic efficacy of bone grafts and biomaterials, such as platelet-rich plasma and platelet-rich fibrin (PRF), for reconstructing lost periodontal structures has been well documented. However, there is limited data regarding the presence of demineralized freeze-dried bone allograft (DFDBA) in an environment with abundant growth factors provided by platelet concentrates. OBJECTIVES: The aim of the study was to compare the clinical and radiographic effectiveness of DFDBA with PRF versus DFDBA alone in the treatment of intrabony defects. MATERIAL AND METHODS: Twenty-four intrabony defects in contralateral sites were randomly assigned to either the DFDBA group or the DFDBA combined with PRF group. Clinical parameters, including the plaque index (PI), the gingival index (GI), probing pocket depth (PPD), relative attachment level (RAL), and radiographic bone fill (RBF), were measured at baseline, and at 6 and 9 months. Paired and unpaired t-tests were used for intraand intergroup comparisons. RESULTS: Both the PI and the GI showed statistically significant improvements from baseline to 9 months. However, the intergroup comparisons did not reveal any significant differences (p < 0.05) between the groups with regard to clinical and radiographic measurements from baseline to 9 months. CONCLUSIONS: Platelet-rich fibrin in combination with DFDBA did not show any additional benefit in terms of reconstructive output in the treatment of intrabony defects compared to the use of DFDBA alone.

[Short-term follow up of treatment effect using one-time one-abutment placement in implant restoration in 35 patients with single posterior teeth loss].

PURPOSE: To evaluate the effet of one-time one-abutment placement on peri-implant tissues. METHODS: Thirty-five patients with single posterior loss were collected, who received definitive abutment at the moment of implant placement. One day and after 1 year of implant loading, radiographic assessment of marginal bone level changes and clinical status of peri-implant soft tissues were conducted. Plaque index, pocket depth as well as sulcus bleeding index were assessed. RESULTS: During 1 year follow-up period after loading, no implant failure was observed. The mean marginal bone loss of implants were (0.225±0.113) mm mesially and (0.439±0.123) mm distally. Standard periodontal probes were used to measure plaque index, probing depth, and gingival crevicular bleeding index immediately after repair and 1 year later. CONCLUSIONS: In the posterior region, one-time one-abutment placement may better protect peri-implant tissues as an ideal treatment protocol.

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.

RNA Technology to Regenerate and Repair Alveolar Bone Defects.

microRNA-200a (miR-200a) targets multiple signaling pathways that are involved in osteogenic differentiation and bone development. However, its therapeutic function in osteogenesis and bone regeneration remains unknown. In this study, we use in vitro and in vivo models to investigate the molecular function of miR-200a overexpression and miR-200a inhibition using a plasmid-based miR inhibitor system (PMIS) on osteogenic differentiation and bone regeneration. Inhibition of miR-200a using PMIS-miR-200a significantly increased osteogenic biomarkers of human embryonic palatal mesenchyme cells and promoted bone regeneration in rat tooth socket defects. In rat maxillary M1 molar extractions, the supporting tooth structures were removed with an implant drill to yield a 3-mm defect in the alveolar bone. A collagen sponge was inserted into the open alveolar defect and PMIS-miR-200a plasmid DNA was added to the sponge and the wound sutured to protect the sponge and close the defect. It was important to remove the existing tooth supporting structure, which can influence alveolar bone regeneration. The alveolar bone was regenerated in 4 wk. The collagen sponge acts to stabilize and deliver the PMIS-miR-200a DNA to cells entering the sponge in the bone defect. We show that mesenchymal stem cells expressing CD90 and Stro-1 enter the sponges, take up the DNA, and express PMIS-miR-200a. PMIS-miR-200a initiates a bone regeneration program in transformed cells in vivo. In vitro inhibition of miR-200a was found to upregulate Wnt and BMP signaling activity as well as Runx2, OCN, Lef-1, Msx2, and Dlx5 associated with osteogenesis. Liver and blood toxicity testing of PMIS-miR-200a-treated rats showed no increase in several biomarkers of liver disease. These results demonstrate the therapeutic function of PMIS-miR-200a for rapid bone regeneration. Furthermore, the studies were designed to demonstrate the ease of use of PMIS-miR-200a in solution and applied using a syringe in the clinic through a simple one-time application.

NF-κB Decoy Oligodeoxynucleotide-Loaded Poly Lactic-co-glycolic Acid Nanospheres Facilitate Socket Healing in Orthodontic Tooth Movement.

Orthodontic space closure following tooth extraction is often hindered by alveolar bone deficiency. This study investigates the therapeutic use of nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides loaded with polylactic-co-glycolic acid nanospheres (PLGA-NfDs) to mitigate alveolar bone loss during orthodontic tooth movement (OTM) following the bilateral extraction of maxillary first molars in a controlled experiment involving forty rats of OTM model with ethics approved. The decreased tendency of the OTM distance and inclination angle with increased bone volume and improved trabecular bone structure indicated minimized alveolar bone destruction. Reverse transcription-quantitative polymerase chain reaction and histomorphometric analysis demonstrated the suppression of inflammation and bone resorption by downregulating the expression of tartrate-resistant acid phosphatase, tumor necrosis factor-α, interleukin-1ß, cathepsin K, NF-κB p65, and receptor activator of NF-κB ligand while provoking periodontal regeneration by upregulating the expression of alkaline phosphatase, transforming growth factor-ß1, osteopontin, and fibroblast growth factor-2. Importantly, relative gene expression over the maxillary second molar compression side in proximity to the alveolus highlighted the pharmacological effect of intra-socket PLGA-NfD administration, as evidenced by elevated osteocalcin expression, indicative of enhanced osteocytogenesis. These findings emphasize that locally administered PLGA-NfD serves as an effective inflammatory suppressor and yields periodontal regenerative responses following tooth extraction.

Minimally invasive non-surgical periodontal therapy of intrabony defects: A prospective multi-centre cohort study.

AIM: To assess the potential benefits of minimally invasive non-surgical therapy (MINST) in teeth with intrabony defects and to explore factors associated with the outcomes. MATERIALS AND METHODS: A multi-centre trial was conducted in 100 intrabony defects in periodontitis patients in private practice. Steps 1 and 2 periodontal therapy including MINST were provided. Clinical and radiographic data were analysed at baseline and 12 months after treatment, with the primary aim being change in radiographic defect depth at 12 months. RESULTS: Eighty-four patients completed the 12-month follow up. The mean total radiographic defect depth reduced by 1.42 mm and the defect angle increased by 3° (both p < .05). Statistically significant improvements in probing pocket depth (PPD) and clinical attachment level (CAL) were seen at 12 months compared to baseline (p < .001). Fifty-six defects (66.7%) achieved pocket closure (PPD ≤ 4 mm) and 49 defects (58.3%) achieved the composite outcome (PPD ≤ 4 mm and CAL gain ≥3 mm). Deeper and narrower angled defects were positively correlated with radiographic and clinical improvements, respectively. CONCLUSIONS: Improvements in clinical and radiographic outcomes were seen after MINST. This study highlights the generalizability and wide applicability of this approach, further supporting its effectiveness in the treatment of intrabony defects. CLINICAL TRIAL REGISTRATION: NCT03741374. https://clinicaltrials.gov/study/NCT03741374?cond=minimally%20invasive%20non%20surgical%20therapy&locStr=UK&country=United%20Kingdom&distance=50&rank=2.

Genetic analysis of impaired healing responses after periodontal therapy in type 2 diabetes: Clinical and in vivo studies.

OBJECTIVE: This study aims to investigate the mechanisms underlying the impaired healing response by diabetes after periodontal therapy. BACKGROUND: Outcomes of periodontal therapy in patients with diabetes are impaired compared with those in patients without diabetes. However, the mechanisms underlying impaired healing response to periodontal therapy have not been sufficiently investigated. MATERIALS AND METHODS: Zucker diabetic fatty (ZDF) and lean (ZL) rats underwent experimental periodontitis by ligating the mandibular molars for one week. The gingiva at the ligated sites was harvested one day after ligature removal, and gene expression was comprehensively analyzed using RNA-Seq. In patients with and without type 2 diabetes (T2D), the corresponding gene expression was quantified in the gingiva of the shallow sulcus and residual periodontal pocket after non-surgical periodontal therapy. RESULTS: Ligation-induced bone resorption and its recovery after ligature removal were significantly impaired in the ZDF group than in the ZL group. The RNA-Seq analysis revealed 252 differentially expressed genes. Pathway analysis demonstrated the enrichment of downregulated genes involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. PPARα and PPARγ were decreased in mRNA level and immunohistochemistry in the ZDF group than in the ZL group. In clinical, probing depth reduction was significantly less in the T2D group than control. Significantly downregulated expression of PPARα and PPARγ were detected in the residual periodontal pocket of the T2D group compared with those of the control group, but not in the shallow sulcus between the groups. CONCLUSIONS: Downregulated PPAR subtypes expression may involve the impaired healing of periodontal tissues by diabetes.

Clinical benefits of autologous platelet concentrate in periodontal intrabony defects: A network meta-analysis of randomized controlled trials.

This study aimed to compare clinical benefits of autologous platelet concentrate with other periodontal regenerative approaches in intrabony defects. An electronic and hand search of studies up to December 2022 was conducted. Randomized controlled trials with at least 6 months of follow-up were identified to compare autologous platelet concentrates with enamel matrix derivative, bone graft, guided tissue regeneration, and open-flap debridement. All approaches involved papilla preservation flap surgery. The outcomes included probing depth reduction, clinical attachment level gain, linear bone fill, and safety. A network meta-analysis and meta-regression were performed. Fifty-seven studies were included in five network meta-analyses. Autologous platelets concentrate and its adjunct treatments achieved significantly greater clinical and radiographic parameters than did open-flap debridement, and had comparable or better performance than other regenerative treatments. Platelet-rich fibrin showed superiority over platelet-rich plasma in probing depth reduction at 6-month follow-up. Minimal pain and improved wound healing were observed in the treatments with autologous platelet concentrate. Meta-regression showed that deeper baseline intrabony defects resulted in larger probing depth reductions, while smoking impaired the effectiveness of regenerative surgeries. Minimal invasive flap designs led to less effect of regenerative materials. Autologous platelet concentrate is a promising biomaterial in periodontal regeneration due to its convenience, safety, and biocompatibility characteristics.

Multiple effects of dose-related GM-CSF on periodontal resorption in deep-frozen grafted teeth: A reverse study.

Autologous tooth grafting is a dental restorative modality based on periodontal ligament healing.Human periodontal ligament stem cells(PDLSCs) are involved in the formation and remodeling of periodontal tissue.Based on previous findings, the proliferation and differentiation of processing cryopreserved periodontal ligament stem cells (PDLSCs) exhibit similarities to those of fresh cells. However, there is evident absorption in the transplanted frozen tooth's roots and bones, with the underlying cause remaining unknown. Granulocyte macrophage colony-stimulating factor(GM-CSF) is named for its produce granulocyte and macrophage precursors from bone marrow precursors, and it also serves as one of the regulatory factors in inflammatory and osteoclast formation. This study aimed to investigate changes in GM-CSF expression in frozen PDLSCs (fhPDLSCs) and evaluate the impact of GM-CSF on PDLSCs with respect to cellular activity and osteogenic ability. The role of GM-CSF in periodontal absorption was further speculated by comparing with IL-1ß. The results revealed a significant increase in GM-CSF levels from fhPDLSCs compared to fresh cells, which exhibited an equivalent inflammatory stimulation effect as 1 ng/ml IL-1ß. Cell viability also increased with increasing concentrations of GM-CSF; however, the GM-CSF from fhPDLSCs was not sufficient to significantly trigger osteoclastic factors. Considering its interaction with IL-1ß and positive feedback mechanism, environments with high doses of GM-CSF derived from fhPDLSCs are more likely to activate osteoclastic responses.Therefore, for frozen tooth replantation, great attention should be paid to anti-inflammation and anti-infection.GM-CSF may serve as a potential therapeutic target for inhibiting periodontal resorption in delayed grafts.

Periodontists and stem cell-based therapy for alveolar bone regeneration: A national survey.

BACKGROUND: Stem cell-based therapy for bone regeneration has received attention in medical settings but has not yet been used in clinical practice for treating alveolar bone defects. The objectives of this study were to explore whether periodontists had heard about this approach, and if so how, how interested they were to learn about it, which attitudes and behavioral intentions they had related to using stem cell-based grafting, and what they would like to know before using this approach. METHODS: Anonymous survey data were collected from 481 members of the American Academy of Periodontology (response rate: 19.41%). RESULTS: Responses showed 35.3% had heard about stem cell-based therapy, mostly from publications (9.6%) and meetings (8.3%); 76.1% wanted to learn about it through in-person continuing education (CE) courses, 68.6% in online CE courses, and 57.1% from manuals; 73% considered this approach promising; and 54.9% preferred it to traditional approaches. It was important to them that it would result in more bone volume (93%), better bone quality (90.4%), and accelerated healing (83.2%). Also, 60.1% considered it likely/very likely that they would adopt this approach, 54% that patients would prefer it, and 62.1% that it would benefit their practice. When asked what they would like to know about this approach, information about short- and long-term outcomes, cost, and logistical considerations were most frequently named. CONCLUSIONS: These findings provide the basis to develop educational interventions for periodontists about this novel approach and inform future research activities aimed to translate this approach to clinical practice.

Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function.

Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.

Do autologous platelet concentrates (APCs) have a role in intra-oral bone regeneration? A critical review of clinical guidelines on decision-making process.

In the past decades, personalized regenerative medicine has gained increased attention. Autologous platelet concentrates (APCs) such as PRP, PRGF, and L-PRF, all serving as a source of a large variety of cells and growth factors that participate in hard and soft tissue healing and regeneration, could play a significant role in regenerative periodontal procedures. This narrative review evaluated the relative impact of APCs in alveolar ridge preservation, sinus floor augmentation, and the regeneration of bony craters around teeth, both as a single substitute or in combination with a xenograft. L-PRF has a significant beneficial effect on alveolar ridge preservation (bone quality). The data for PRGF are less convincing, and PRP is controversial. L-PRF can successfully be used as a single substitute during transcrestal (≥3.5 mm bone gain) as well as 1-stage lateral window sinus floor elevation (>5 mm bone gain). For PRGF and especially PRP the data are very scarce. In the treatment of bony craters around teeth, during open flap debridement, L-PRF as a single substitute showed significant adjunctive benefits (e.g., >PPD reduction, >CAL gain, >crater depth reduction). The data for PRP and PRGF were non-conclusive. Adding PRP or L-PRF to a xenograft during OFD resulted in additional improvements (>PPD reduction, >CAL gain, >bone fill), for PRGF no data were found. Autologous platelet concentrates demonstrated to enhance bone and soft tissue healing in periodontal regenerative procedures. The data for L-PRF were most convincing. L-PRF also has the advantage of a greater simplicity of production, and its 100% autologous character.

Infrared laser therapy decreases systemic oxidative stress and inflammation in hypercholesterolemic mice with periodontitis.

BACKGROUND: Near-infrared irradiation photobiomodulation (NIR-PBM) has been successfully used in periodontal treatment as an adjuvant tool to locally improve cell function and regeneration. Although the relationship between periodontitis and systemic disease constitutes an important aspect of periodontal clinical research, the systemic effects of NIR-PBM in periodontitis are not well known. In this study, we aimed to investigate the effects of NIR-PBM on systemic oxidative stress and inflammation in an apolipoprotein E (ApoE) knockout mouse model of periodontal disease (PD). METHODS: We evaluated alveolar bone loss by measuring the distance from the cementoenamel junction (CEJ) to the alveolar bone crest (ABC), reactive oxygen species (ROS) production in blood cells, inflammatory activity, plasma cholesterol levels, and lipid peroxidation levels in three experimental groups: (1) ApoEC, control group without intervention; (2) ApoEP, first molar ligation-induced periodontitis for 4 weeks; and (3) ApoEP + PBM, exposed to 808 nm continuous wave, ø ~ 3 mm2, 100 mW, 60 s of NIR-PBM for 7 consecutive days after 4 weeks of periodontitis. At the end of the experimental protocols, ApoEP mice presented significantly increased alveolar bone loss, ROS production, inflammatory activity, plasma cholesterol, and lipid peroxidation levels compared to the ApoEC group (P < 0.05). NIR-PBM for 7 days in the ApoEP + PBM mice significantly decreased systemic ROS production, inflammatory response, plasma cholesterol, and lipid peroxidation levels, similar to those found in the ApoEC group (P > 0.05). However, it was not capable of preventing alveolar bone loss (P > 0.05 compared to ApoEP mice). CONCLUSION: A 7-day treatment with NIR-PBM effectively reduces systemic oxidative stress and inflammatory parameters in hypercholesterolemic mice with PD. However, more studies with longer evaluation times are needed to confirm the systemic effects of locally applied NIR-PBM on PD associated with hypercholesterolemia.

Dental Pulp Stem Cell-Derived Exosomes Regulate Anti-Inflammatory and Osteogenesis in Periodontal Ligament Stem Cells and Promote the Repair of Experimental Periodontitis in Rats.

Purpose: Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with tissue regeneration. Periodontitis is an immune inflammation and tissue destructive disease caused by plaque, resulting in alveolar bone loss and periodontal epithelial destruction. It is not clear whether DPSC-EXO can be used as an effective therapy for periodontal regeneration. The purpose of this study was not only to verify the effect of DPSC-EXO on reducing periodontitis and promoting periodontal tissue regeneration, but also to reveal the possible mechanism. Methods: DPSC-EXO was isolated by ultracentrifugation. Then it characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western Blot. In vitro, periodontal ligament stem cells (PDLSCs) were treated with DPSC-EXO, the abilities of cell proliferation, migration and osteogenic potential were evaluated. Furthermore, we detected the expression of IL-1ß, TNF-αand key proteins in the IL-6/JAK2/STAT3 signaling pathway after simulating the inflammatory environment by LPS. In addition, the effect of DPSC-EXO on the polarization phenotype of macrophages was detected. In vivo, the experimental periodontitis in rats was established and treated with DPSC-EXO or PBS. After 4 weeks, the maxillae were collected and detected by micro-CT and histological staining. Results: DPSC-EXO promoted the proliferation, migration and osteogenesis of PDLSCs in vitro. DPSC-EXO also regulated inflammation by inhibiting the IL-6/JAK2/STAT3 signaling pathway during acute inflammatory stress. In addition, the results showed that DPSC-EXO could polarize macrophages from the M1 phenotype to the M2 phenotype. In vivo, we found that DPSC-EXO could effectively reduce alveolar bone loss and promote the healing of the periodontal epithelium in rats with experimental periodontitis. Conclusion: DPSC-EXO plays an important role in inhibiting periodontitis and promoting tissue regeneration. This study provides a promising acellular therapy for periodontitis.

Stem cell-based therapy in periodontal regeneration: a systematic review and meta-analysis of clinical studies.

BACKGROUND: Periodontitis is a common and chronic inflammatory disease characterized by irreversible destruction of the tooth surrounding tissues, especially intrabony defects, which eventually lead to tooth loss. In recent years, stem cell-based therapy for periodontitis has been gradually applied to the clinic, but whether stem cell-based therapy plays a positive role in periodontal regeneration is unclear at present. METHODS: The clinical studies related to the evaluation of mesenchymal stem cells for periodontal regeneration in PubMed, Cochrane Central Register of Controlled trials (CENTRAL), Web of Science (WOS), Embase, Scopus, Wanfang and China national knowledge infrastructure (CNKI) databases were searched in June 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell free therapy for the treatment periodontitis, and to have a follow-up for at least six months. Two evaluators searched, screened, and assessed the quality and the risk of bias in the included studies independently. Review Manager 5.4 software was used to perform the meta-analysis, and GRADEpro GDT was used to evaluate the level of the evidence. RESULTS: Five randomized controlled trials (RCTs) including 118 patients were analyzed. The results of this meta-analysis demonstrated that stem cell-based therapy showed better therapeutic effects on clinical attachment level (CAL) (MD = - 1.18, 95% CI = - 1.55, - 0.80, P < 0.00001), pocket probing depth (PPD) (MD = - 0.75, 95% CI = - 1.35, - 0.14, P = 0.020), and linear distance from bone crest to bottom of defect (BC-BD)( MD = - 0.95, 95% CI = - 1.67, - 0.23, P = 0.010) compared with cell-free group. However, stem cell-based therapy presented insignificant effects on gingival recession (P = 0.14), linear distance from cementoenamel junction to bottom of defect (P = 0.05). CONCLUSION: The results demonstrate that stem cell-based therapy may be beneficial for CAL, PPD and BC-BD. Due to the limited number of studies included, the strength of the results in this analysis was affected to a certain extent. The high-quality RCTs with large sample size, multi-blind, multi-centric are still required, and the methodological and normative clinical study protocol should be established and executed in the future.

Molecular Basis beyond Interrelated Bone Resorption/Regeneration in Periodontal Diseases: A Concise Review.

Periodontitis is the sixth most common chronic inflammatory disease, destroying the tissues supporting the teeth. There are three distinct stages in periodontitis: infection, inflammation, and tissue destruction, where each stage has its own characteristics and hence its line of treatment. Illuminating the underlying mechanisms of alveolar bone loss is vital in the treatment of periodontitis to allow for subsequent reconstruction of the periodontium. Bone cells, including osteoclasts, osteoblasts, and bone marrow stromal cells, classically were thought to control bone destruction in periodontitis. Lately, osteocytes were found to assist in inflammation-related bone remodeling besides being able to initiate physiological bone remodeling. Furthermore, mesenchymal stem cells (MSCs) either transplanted or homed exhibit highly immunosuppressive properties, such as preventing monocytes/hematopoietic precursor differentiation and downregulating excessive release of inflammatory cytokines. In the early stages of bone regeneration, an acute inflammatory response is critical for the recruitment of MSCs, controlling their migration, and their differentiation. Later during bone remodeling, the interaction and balance between proinflammatory and anti-inflammatory cytokines could regulate MSC properties, resulting in either bone formation or bone resorption. This narrative review elaborates on the important interactions between inflammatory stimuli during periodontal diseases, bone cells, MSCs, and subsequent bone regeneration or bone resorption. Understanding these concepts will open up new possibilities for promoting bone regeneration and hindering bone loss caused by periodontal diseases.

Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function / 国际口腔科学杂志·英文版

Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.

Carga inmediata de implantes extra cortos en sectores posteriores. Estudios retrospective con tres modelos de carga: 24, 48 hs y 7 días / Immediate loading of extra short implants in posterior sectors. Retrospective study with three loading models: 24 hs, 48 hs and 7 days

Los implantes extra-cortos son cada vez más utili-zados en la práctica clínica diaria. La utilización de estos implantes con carga inmediata supone un reto añadido. Clásicamente se ha postulado que la carga inmediata debe realizarse después de 24 horas de la cirugía. En la siguiente serie de casos analizamos diferentes tiempos a la hora de realizar la carga in-mediata y su posible repercusión. Fueron recolec-tados de forma retrospectiva datos sobre casos de implantes extra-cortos (5,5 y 6,5 mm) en los que fue realizada una carga inmediata en sectores poste-riores. El implante fue la unidad de análisis para la estadística descriptiva en cuanto a la localización, dimensiones del implante, y mediciones radiográ-ficas. El paciente fue la unidad de medida para el análisis de la edad, sexo y la historia clínica. La prin-cipal variable estudiada fue la supervivencia de los implantes extra-cortos con carga inmediata en tres períodos de tiempo determinados: 24 hs, 48 hs y 7 días y como variables secundarias se han estudiado, la estabilidad del hueso crestal en general y en los tres períodos de carga anteriormente mencionados, las complicaciones protésicas y la supervivencia de las prótesis. Fueron reclutados 74 pacientes en los que se insertaron 146 implantes que cumplieron con los criterios de inclusión. Todos los implantes fueron cargados mediante carga inmediata en tres perío-dos determinados de tiempo: 24 hs (40 implantes), 48 hs (42 implantes) y 7 días (42 implantes). Todos los implantes fueron ferulizados a otros implantes ge-nerándose puentes de dos o más unidades, con di-ferente longitud. En el grupo de implantes con carga inmediata en 24 hs la media de la pérdida ósea distal de todos los implantes fue de 0,21 mm (+/-0,84) y la media de la pérdida ósea mesial en este grupo fue de 0,33 mm (+/- 0,53). En el grupo de carga inmediata en 48 hs, la media de la pérdida ósea distal de todos los implantes fue de 0,20 mm (+/- 0,82) y la media de la pérdida ósea mesial fue de 0,22 mm (+/- 0,81). En el grupo de carga de 7 días, la pérdida ósea me-sial del grupo fue de 0,28 mm (+/- 0,51) y la media de la pérdida ósea distal fue de 0,17 mm (+/- 0,81). Cuando comparamos las medias de pérdida ósea me-sial y distal entre los tres grupos, no se observaron diferencias estadísticamente significativas (mesial p=0,062, distal p=0,067). En conclusión, no se obser-varon diferencias significativas en la pérdida ósea crestal ni en la supervivencia de los implantes cortos entre los 3 tiempos estudiados de aplicación de car-ga inmediata. Por ello, utilizar cualquiera de los tres protocolos puede ser adecuado, mientras se realice un correcto análisis de la situación clínica de cada paciente (AU)

Extra-short implants are increasingly used in daily clinical practice. The use of these implants with immediate loading poses an added challenge. Classically it has been postulated that immediate loading should be performed 24 hrs after surgery. In the following case series, we analyze different times of immediate loading and their possible repercussions. We retrospectively collected data on cases of extra-short implants (5.5 and 6.5 mm) in which immediate loading was performed in posterior sectors. The implant was the unit of analysis for descriptive statistics in terms of location, implant dimensions, and radiographic measurements. The patient was the unit of measurement for the analysis of age, sex and medical history. The main variable studied was the survival of immediately loaded extra-short implants in three specific time periods: 24 hrs, 48 hrs and 7 days. Secondary variables studied were crestal bone stability in general and in the three loading periods mentioned above, prosthetic complications and prosthesis survival. Seventy-four patients were recruited and 146 implants that met the inclusion criteria were inserted. All implants were loaded by immediate loading in three specific time periods: 24 hrs (40 implants), 48 hrs (42 implants) and 7 days (42 implants). All implants were splinted to other implants generating bridges of two or more units, with different lengths. In the 24-hr immediate loading group the mean distal bone loss of all implants was 0.21 mm (+/- 0.84) and the mean mesial bone loss in this group was 0.33 mm (+/- 0.53). In the 48-hr immediate loading group, the mean distal bone loss for all implants was 0.20 mm (+/- 0.82) and the mean mesial bone loss was 0,22 mm (+/- 0,81). In the 7-day loading group, the mesial bone loss of the group was 0.28 mm (+/- 0.51) and the mean distal bone loss was 0.17 mm (+/- 0.81). When we compared the mean mesial and distal bone loss between the three groups there were no statistically significant differences (mesial p=0.062, distal p=0.067). In conclusion, no significant differences were observed in crestal bone loss or in the survival of short implants between the 3 immediate load application times studied. Therefore, using any of the three protocols can be appropriate, as long as a correct analysis of the clinical situation of each patient is performed (AU)