bone regeneration

 Recently, the positive effects of photobiomodulation (PBM) and nano-bone on bone regeneration have garnered significant attention. The purpose of the research was to assess the impact of PBM and nano-bone on the process of mandibular bone repair in mice.

 A 4-mm diameter bone defect was created in the left mandibular angle of 24 mice separated into 4 equal groups: group I: control; group II: PBM by irradiation at 100 mW of a 980 nm diode laser for one minute (three sessions per week; day on and day off); group III: nano-bone; group IV: PBM with nano-bone. Every group was sectioned into 3 equal subgroups corresponding to the evaluation method period: (A) one week, (B) two weeks, and (C) four weeks. Histological examination was done with hematoxylin, eosin, and Masson’s Trichrome after one, two and four weeks for inflammation, bone defect coverage, vascularization within the newly formed bone, and new bone formation. A statistical analysis of the data was done, and the percentage values were presented using chi-square. The significance level was set at a P-value≤0.05 within all tests.

 In general, by histological examination of the mandibular bone defect of the rats, the intensity of inflammation was the least in group IV when compared with groups II and III and the control group at all evaluation periods (P<0.001). Also, group IV showed a high significant rise in the percentage of new bone formation following four weeks when compared with the control (P≤ 0.001) and groups II and III (P<0.001).

 The present research results confirmed that the combination of PBM and nano-bone can aid in the repair of mandibular bone abnormalities. This animal study suggests that the use of PBM and nano-bone should be investigated further in clinical studies.

Dental implant placement in the esthetic zone is associated with challenges for clinicians. The best esthetic outcome of this procedure can be obtained through precise management of hard and soft tissue. Orthodontic forced eruption (OFE) has presented an alternative approach to augment hard and soft tissues, which can be applied rapidly or slowly. OFE of hopeless teeth with its periodontal attachment results in a favorable implant preparation site. Therefore, the present systematic review evaluated the effect of implant site preparation using OFE in hopeless teeth. A complete electronic search was performed in PubMed/MEDLINE, Scopus, and Google Scholar from June 2020 to November 2023. The search was limited to clinical English language studies. Studies were excluded if OFE was performed without implant placement. Finally, 15 studies with a total of 21 teeth, all located in the maxillary anterior region, were included in this study. In eight studies, bone grafting procedures were performed before implant placement. Using OFE could rapidly prepare the implant site by enhancing hard and soft tissues. However, additional interventions like guided bone regeneration should be considered case-dependent.

The purpose of this study was to review the literature on the efficacy of different surgical regenerative methods for peri-implantitis treatment.

A preliminary search was conducted in seven electronic databases. The studies included in the analysis implemented surgical regenerative treatment in at least one study group. Baseline and follow-up values for bleeding on probing (BoP), pocket depth (PD), plaque index (PI), bone level (BL), and bone gain (BG) were extracted. The standardized mean difference (SMD) was calculated using Cohen’s d or Hedges’ g, and a random-effects-restricted maximum likelihood (REML) method was applied for the meta-analysis.

Fifteen studies were included in the qualitative synthesis. The meta-analysis was performed on six studies comparing regenerative techniques that involved bone grafts with those that did not. The overall effect size for using bone grafts at the one-year follow-up was 0.04 (95% CI: -0.26‒0.35; P = 0.78) for BoP, -0.08 (95% CI: -0.42‒0.27; P = 0.66) for PD, 0.37 (95% CI: 0.08‒0.65; P = 0.01) for PI, -0.44 (95% CI: -0.84 to -0.03; P = 0.03) for BL, and 0.16 (95% CI:-0.68‒1.01; P = 0.70) for BG.

Various materials have been employed for peri-implant defect filling and coverage. A bone substitute did not significantly improve BoP, PD, and BG values, while PI and BL were significantly ameliorated at one-year follow-up. However, recommending a single unified protocol as the most effective for surgical regenerative treatment of peri-implantitis was not feasible.

 Xenograft bone substitutes can be obtained from different animals and processed using various methods. The present in vivo study evaluated bone regeneration after using three types of xenografts with different sources in critical-sized bone defects in rabbit calvaria.

 Four 8-mm defects were created in calvaria of 14 New Zealand and white male rabbits. Three out of four defects were filled with xenografts of bovine, camel, and ostrich sources. The fourth defect was left unfilled as the control group. Seven rabbits were sacrificed after eight weeks and seven others after 12 weeks. Micro-CT imaging and histologic evaluation were further performed on dissected calvarias.

 After 8 and 12 weeks, the highest and lowest percentages of new bone formation were observed in the camel (27.71% and 41.92%) and control (11.33% and 15.96%) groups, respectively. In the case of residual material, the ostrich group had the most value after eight weeks (53%), while after 12 weeks, it was highest in the camel group (37%). Micro-CT findings were consistent with histologic results.

 Although all three xenografts can be good choices for treating bone defects, camel-sourced xenograft seemed to be better than the other two groups. The origin and processing procedures of xenografts affected their final characteristics, which should be considered for clinical use.

Dabigatran belongs to the new generation of direct oral anticoagulants (DOACs). Its advantages are oral administration and no need for international normalized ratio (INR) monitoring. Although its use has increased, its potential side effects on bone healing and remodeling have not been fully investigated. The present study aimed to evaluate the possible effects of dabigatran on early bone healing.

Sixteen male Wistar rats were divided into two groups; in group A, 20-mg/kg dabigatran dose was administered orally daily for 15 days, while group B served as a control. Two circular bone defects (d=6 mm) were created on either side of the parietal bones. Two weeks after surgery and euthanasia of the animals, tissue samples (parietal bones that contained the defects) were harvested for histological and histomorphometric analysis. Statistical analysis was performed with a significance level of α=0.5.

No statistically significant differences were found between the two groups regarding the regenerated bone (21.9% vs. 16.3%, P=0.172) or the percentage of bone bridging (63.3% vs. 53.5%, P=0.401).

Dabigatran did not affect bone regeneration, suggesting that it might be a safer drug compared to older anticoagulants known to lead to bone healing delay.

Developing cell-based therapeutic methods for differentiating various stem cells into dental tissues could be a revolutionary step toward using cell therapy for dental diseases. In the present study, we systematically reviewed the literature to determine the efficiency of stem cells in treating various dental diseases.

Using the search words “stem cell” and “dental disease” as well as all their equivalents and similar terms, we performed a literature search in September 2020 in the electronic databases: PubMed, Scopus, Science Direct, Web of Science, Embase, Ovid, and Google Scholar. The investigation was limited to clinical trials written in the English language.

Overall, 22 articles with 400 study patients were found and used for qualitative data synthesis. Findings showed that various stem cells with different origins can be used for cell therapy of various dental diseases such as pulp necrosis, traumatic dental injuries, maxillofacial bony defects, impacted third molars, etc.

Stem cell therapy is an efficient method for treating dental diseases. It can regenerate whole dental pulp and may be useful for treating tooth injuries due to trauma.

With the advances in technology, the use of natural materials has broadened. Acemannan is the main polysaccharide in aloe vera plant. It is a natural and biocompatible polymer with low toxicity. The acemannan monomers include mannose, glucose and galactose. Due to its biological properties, acemannan could be useful in bone regeneration.  The aim of this study was to investigate the effect of acemannan/aloe vera on bone regeneration and extraction socket healing.  

In this review article, an electronic search was conducted in PubMed and Scopus from 1996 to June 2022. Relevant data based on clinical indications were extracted. Twenty original articles, including 4 in vitro studies, 8 animal, and 8 human studies were reviewed. The inclusion criterion was articles that directly and originally evaluated the correlation of bone regeneration and acemannan/aloe vera.

Over 30 studies were found in this field by database searching. According to the results, the proposed items could be categorized into 3 major groups of animals, human, and in vitro studies. Animal studies were divided into two groups of bone defect regeneration and extraction socket healing. Also, human studies were divided into two groups of bone defect regeneration and sinus floor elevation/guided bone regeneration surgeries. All studies reported positive effect of Acemannan/aloe vera on bone healing and regeneration.

Acemannan/aloe vera may be considered as a bioactive molecule due to induction and acceleration of bone formation.

Statement of the Problem:

 Currently, the reconstruction of bone defects with new platelet concentrates is considered a significant challenge in periodontics.

This study aimed to evaluate advanced- platelet rich fibrin (A-PRF) and leukocyte- and platelet rich fibrin’s (L-PRF) effects on the proliferation and differentiation of MG-63 cells.

In this in vitro study, blood samples of five healthy non-smoking volunteers were collected and immediately centrifuged according to the two protocols of Choukroun and Ghanaati, without adding any anticoagulants, to prepare L-PRF and A-PRF. After freezing the clots for one hour, they were crushed and centrifuged once more. After culturing MG-63 cells, the effects of 20%, 10%, 1%, and 0.5% concentrations of A-PRF and L-PRF extracts on cell proliferation and mineralization were evaluated by methyl thiazolyl tetrazolium (MTT) assay and Alizarin Red staining, respectively.

Generally, survival and proliferation in the L-PRF group at both time intervals were higher than the A-PRF group and increased with increasing the extract concentration. However, in the A-PRF group, there were no significant differences between the different concentrations, and only the number of cells increased over time. After three days, in the study on mineralization, nodule formation was observed only in the positive control group (osteogenic). In seven days, mineralized nodules were formed in all groups with different concentrations of A-PRF, but not in any of the L-PRF groups.

According to the results, L-PRF increased proliferation, and A-PRF exerted a positive effect on the differentiation of MG-63 cells.

The study aimed to assess the histologic and histomorphometric effects of leukocyte platelet-rich fibrin (L-PRF) and nano-hydroxyapatite (nHA) on the regeneration of calvarial bone defects in rabbits.

Four defects were created in the calvaria bone of 14 New Zealand rabbits and filled with L-PRF clot, nHA, or a combination of L-PRF and nHA. The fourth defect remained unfilled to serve as the control group. The rabbits were sacrificed either at 4 or at 8 weeks, and the specimens were evaluated for the type and degree of inflammation, foreign body reaction, new bone formation, and residual biomaterial particles.

The histomorphometric analysis revealed that L-PRF significantly enhanced osteogenesis (P<0.05), and the number of subsequent remnant bodies in the L-PRF group was not significantly different from the control group (P>0.05). The results of the histologic analysis showed that the frequency of central bone regeneration significantly increased in prolonged periods (P<0.05). There was no significant difference in the utilized biomaterials concerning subsequent bleeding, inflammation, foreign body reaction, and lateral bone regeneration between 4 and 8 weeks of treatment (P>0.05).

The results showed that L-PRF was a suitable option for the induction of bone regeneration with fewer remnant bodies. However, future clinical studies are required to assess the efficacy of these biomaterials in the clinical setting.

Background:

 Bone reconstruction with appropriate quality and quantity for dental implant replacement in the alveolar ridge is a challenge in dentistry. As dental pulp stem cells (DPSCs) could be a new perspective in bone regeneration in the future, this study investigated the bone regeneration process by DPSCs.

Methods: 

Electronic searches for articles in the PubMed, EMBASE, and Scopus databases were completed until 21 April 2022. The most important inclusion criteria for selecting in vivo studies reporting quantitative data based on new bone volume and new bone area. The quality assessment was performed based on Cochrane’s checklist.

Results: 

After the title, abstract, and full-text screening of 762 studies, 23 studies were included. A meta-analysis of 70 studies that reported bone regeneration based on new bone area showed a statistically significant favorable influence on bone tissue regeneration compared to the control groups (P<0.00001, standardized mean difference [SMD]=2.40, 95% CI: 1.55‒3.26; I 2=83%). Also, the meta-analysis of 14 studies that reported new bone regeneration based on bone volume showed a statistically significant favorable influence on bone tissue regeneration compared to the control groups (P=0.0003, SMD=1.85, 95% CI: 0.85‒2.85; I2=84%).

Conclusion: 

This systematic review indicated that DPSCs in tissue regeneration therapy significantly affected bone tissue complex regeneration. However, more and less diverse preclinical studies will enable more powerful meta-analyses in the future.

We aimed to systematically review the animal studies that have investigated the efficacy of periodontal ligament stem cells (PDLSCs) in bone regeneration.

Web of science, Scopus, PubMed, Embase, Cochrane Library, and ProQuest were searched to September 2022 for animal studies investigating bone regeneration using PDLSCs.

Twenty studies were included. Calvaria and alveolar defects were treated with stem cells. The cells were mainly carried with hydrogel, hydroxyapatite, and collagen scaffolds. PDLSCs promoted osteogenesis compared with cell-free scaffolds, except in one study where biphasic calcium phosphate block scaffolds alone or with Bone morphogenic protein 2 had superior outcomes in calvaria defects. Controversial results were reported when comparing the osteogenic potential of PDLSCs and bone marrow stem cells. Two studies reported higher potential in BMSCs, and two others reported higher bone formation and more bone quality in PDLSCs.

With the limitations of this study, PDLSCs might have promising potential to accelerate bone regeneration in artificial defects; however, due to high heterogeneity in the outcomes of the present studies, before moving forward to human experiments, further preclinical in vivo studies are needed.

A 29-year-old female patient was referred to the Department of Oral And Maxillofacial Surgery in Taleghani Hospital of Shahid Beheshti University of Medical Science, Tehran, Iran, in 2019, complaining of increased volume and pain in the posterior mandibular region. Cone-beam computed tomography and multislice computed tomography were performed, and an incisional biopsy was done. The histopathologic examination confirmed the diagnosis of Odontogenic Keratocyst (OKC). Surgical treatment was performed with marsupialization. After a year of follow-up, the resultant small-sized cyst was curetted, and Leukocyte-Platelet‑Rich Fibrin (LPRF) was placed in the bony depression. The significant healing of the lesion was noted on regular follow-up visits with complete resolution at 15 months. This report showed that the application of LPRF might accelerate the healing of soft tissues and bone regeneration with no inhibitory effect on the natural healing process.

This narrative review of the literature aims to analyze the utilization of stromal vascular fraction (SVF)and decellularized extracellular matrices (dECMs) in various pathologies related to orthopedic surgery.

A literature search was carried out in PubMed on February 15, 2022, using “Stroma Vascular Fraction andOrthopedic Surgery” and “Decellularized Extracellular Matrices and Orthopedic Surgery” as keywords. A total of 278articles were found, of which 28 papers were selected because they seemed to be the most appropriate concerningthe title of the article.

The reported results have shown that intra-articular injection of SVF seems to be a safe and efficaciousmethod for managing knee osteoarthritis (OA). Platelet-rich plasma (PRP) and SVF are safe and effective managementfor intractable Achilles tendinopathy in humans, although subjects treated with SVF recover earlier. There are promisingresults in utilizing adipose-derived mesenchymal stromal cells in chronic lateral epicondylitis of the elbow in athletes.Ready-to-use ECM/SVF gel seems to be a good therapeutic option promoting the regeneration of the articular cartilagein subjects with injuries of the cartilage. The SVF can safely be used to treat diabetic subjects suffering from chronicfoot ulcers.

There are scarce high-quality data for utilizing cell-based approach in soft tissue injuries of the knee inathletes. Experimental studies indicate that SVF could be a new option to osseous regeneration. Other experimentalstudies support the utilization of dECMs as a scaffold for the regeneration of large osseous defects, cell-derived dECMsscaffolds to repair articular cartilage injuries, and utilization of xenogeneic acellular muscles to manage volumetricmuscle loss where there is a lack of donor site.Intra-articular injections of SVF seems to be a safe and efficacious method for managing OA of the knee joint. Plateletrichplasma (PRP) and SVF are safe and efficacious methods for the management of intractable Achilles tendinopathyin humans, although subjects treated with SVF recover earlier. 

Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is an essential stage in bone formation. Autophagy plays a pivotal role in the self-renewal potential and pluripotency of stem cells. This study aimed to explore the function of autophagy-related genes during osteogenic differentiation of BMSCs.

The differentially expressed autophagy-related genes (ARGs) were obtained from the GEO and HADb databases. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using R software. The PPI and hub gene mining networks were constructed using the STRING database and Cytoscape. Finally, the RT-qPCR was conducted to validate the expression level of ARGs in BMSCs.

Thirty-seven differentially expressed ARGs were finally obtained, including 12 upregulated and 25 downregulated genes. GO and KEGG enrichment analysis showed that most of these genes were enriched in apoptosis and autophagy. The PPI network revealed strong interactions between differentially expressed ARGs. The expression level of differentially expressed ARGs tested by RT-qPCR showed 6 upregulated ARGs, including FOXO1, MAP1LC3C, CTSB, FOXO3, CALCOCO2, FKBP1A, and 4 downregulated  ARGs, including MAPK8IP1, NRG1, VEGFA, and ITGA6 were consistent with the expression of high-throughput sequencing data.

We identified 37 ARGs during osteogenic differentiation using bioinformatics analysis. FOXO1, MAP1LC3C, CTSB, FOXO3, CALCOCO2, FKBP1A, MAPK8IP1, NRG1, VEGFA, and ITGA6 may regulate osteogenic differentiation of hBMSCs by involving autophagy pathway. This study provides new insight into the osteogenic differentiation of hBMSCs and may be available in developing therapeutic strategies for maxillofacial bone defects.

Considering the efficacy of platelet-rich fibrin (PRF) in enhancement of healing by releasing growth factors, this study aimed to assess the efficacy of PRF application as a protective barrier right beneath the sinus membrane on the Schneiderian membrane thickness following sinus floor augmentation.  

This randomized controlled split-mouth clinical trial was conducted on 18 patients (36 sinuses) who required bilateral sinus floor augmentation. Two patients (n=4 sinuses) were excluded due to chronic sinusitis, and one patient due to perioperative sinus membrane perforation. Fifteen patients (n=30 sinuses) were finally assessed. In the test side, PRF membrane was placed beneath the Schneiderian membrane while augmentation was performed without a PRF membrane in the control side. Cone-beam computed tomography (CBCT) scans were taken preoperatively, and at 1 week and 2 months postoperatively, and the Schneiderian membrane thickness was compared at the two sides using ANOVA and a post-hoc test.

The mean membrane thickness was 1.85±0.85 mm in the control and 2.17±0.87 mm in the test group before the intervention (P=0.6). At 1 week, the mean thickness was 2.45±1.22 in the control and 3.77±1.42 mm in the case group (P=0.2). At 2 months, the mean thickness was 2.54±1.66 mm in the control and 1.71±1.31 mm in the test group (P=0.2). ANOVA showed no significant difference between the two groups at any time point (P>0.05).

Application of PRF under the Schneiderian membrane in sinus floor augmentation had no significant effect on the Schneiderian membrane thickness.

Statement of the Problem: 

Osteoblastic differentiation of periodontal ligament stem cells (PLSCs) is essential for alveolar bone regeneration.

The purpose of this study was to compare the potential of two β-tricalcium phosphate (βTCP) products to induce osteoblastic differentiation of human PLSCs.

In this in vitro study, human PLSCs were cultured in mediums supplemented with Guidor Easy-Graft [βTCP+polylactide-co-glycolide(PLCG)+n-methyl-2-pyrrolidone(NMP)] [Sunstar Company, Swiss] or Sorbone [βTCP] [Meta Company, South Korea] as two alloplasts experimental groups, mesenchymal cells differentiated into osteoblasts without alloplast as positive control group, and mesenchymal cells without osteoblastic induction as negative control group. Osteoblastic differentiation was evaluated using Alizarine Red staining and spectrophotometry to assay calcium deposits and real-time polymerase chain reaction to examine expression of alkaline phosphatase (ALP) and osteopontin (OPN) antigens on day 21. Data were analyzed by using SPSS 22 software and one-way ANOVA and Bonferoni tests (p< 0.05).

Spectrophotometry confirmed that calcium deposits were higher in Guidor Easy-Graft group compared to Sorbone group (p< 0.001) and higher in two experimental groups than controls (p< 0.05). According to real-time polymerase chain reaction, level of ALP expression was higher in Sorbone than Guidor and the levels of Guidor, positive control and negative control were equal; OPN levels of the positive control were more than the other groups. OPN levels of Sobone, Guidor and negative control were the same.

These findings indicated that Guidor Easy-Graft and Sorbone enhanced differentiation of human PLSCs to osteoblasts, and could be employed as appropriate bone-graft materials.

Bone regeneration is a desired treatment outcome in implant dentistry. The primary goal of the current investigation was to assess the joint effect of low-level laser therapy (LLLT) and leukocyte- and platelet-rich fibrin (PRF) on new bone formation.

During this experiment study, forty bone defects (8 mm in diameter) were generated in the calvaria of ten New-Zealand white rabbits. defects were filled with autogenous bone defined as the control group, autogenous bone with leukocyte- and PRF (PRF group), autogenous bone and low-level diode laser radiation (LLLT group), and autogenous bone with leukocyte- and PRF and low-level laser radiation (LP group). Laser irradiation was done every second day for 2 weeks after surgery. Five rabbits were randomly selected to be sacrificed on postoperative weeks 4 and 8. On one and two-month post-surgery, histological and histomorphometric parameters including bone formation, fibroblast, and osteoblast were assessed.

The histological panel depicted that the ratio of fresh bone formation increased at one-and two-month postsurgery in all treatment groups compared to the control group. The most favorable results were seen in the LP group, followed by the PRF group. Based on the ANOVA test, bone neoformation was statistically significant in the LP group in comparison with the control group (P<0.001). One-month post-surgery, a higher degree of fibroblast was seen in the control group, while the last place was for LP group (118.6 ± 6.9 vs. 24.0 ± 3.2). In the PRF group, the percentage ofbone formation was higher than that in the control group (13.2 ± 2.8 vs. 2.0 ± 1.2), but no significant difference when compared to the LP group (13.2 ± 2.8 vs. 19.0 ±.3.8).

The combined L-PRF and LLLT was more likely to have a positive effect on accelerating bone regeneration and reducing fibrosis.