Oral Bone Research Articles

A dual osteoconductive-osteoprotective implantable device for vertical alveolar ridge augmentation

Repair of large oral bone defects such as vertical alveolar ridge augmentation could benefit from the rapidly developing additive manufacturing technology used to create personalized osteoconductive devices made from porous tricalcium phosphate/hydroxyapatite (TCP/HA)-based bioceramics. These devices can be also used as hydrogel carriers to improve their osteogenic potential. However, the TCP/HA constructs are prone to brittle fracture, therefore their use in clinical situations is difficult. As a solution, we propose the protection of this osteoconductive multi-material (herein called “core”) with a shape-matched “cover” made from biocompatible poly-ɛ-caprolactone (PCL), which is a ductile, and thus more resistant polymeric material. In this report, we present a workflow starting from patient-specific medical scan in Digital Imaging and Communications in Medicine (DICOM) format files, up to the design and 3D printing of a hydrogel-loaded porous TCP/HA core and of its corresponding PCL cover. This cover could also facilitate the anchoring of the device to the patient's defect site via fixing screws. The large, linearly aligned pores in the TCP/HA bioceramic core, their sizes, and their filling with an alginate hydrogel were analyzed by micro-CT. Moreover, we created a finite element analysis (FEA) model of this dual-function device, which permits the simulation of its mechanical behavior in various anticipated clinical situations, as well as optimization before surgery. In conclusion, we designed and 3D-printed a novel, structurally complex multi-material osteoconductive-osteoprotective device with anticipated mechanical properties suitable for large-defect oral bone regeneration.

Exploring the role of Vitamin D in oral health and bone remodeling: Implications for apical periodontitis and tooth loss

Exploring the role of Vitamin D in oral health and bone remodeling: Implications for apical periodontitis and tooth loss

Clinical Evaluation of Zirconia and Stainless-Steel crowns in Primary Molars - A Randomized Control Trial

Background and Aim: Aesthetic alternatives to stainless steel crown for restoring primary molars attain a growing interest. The aim of the study was clinical evaluation and comparison of zirconia and stainless steel crown in primary molars (clinical and radiograph) Methods: A randomized controlled study was conducted on children of age group of 5 to 8 years of age visiting, KVG Dental College and Hospital, Sullia and who were meet the inclusion criteria of the study. The study population was randomly divided into two groups of 24 each. Group I: stainless steel crown, Group II: zirconia crown. Post endodontic tooth preparation was done and selected stainless steel and zirconia crowns followed by cemented using type 1 glass ionomer cement. The subjects was be recalled after 3, 6 and 9 months to check gingival index, oral hygiene index and bone health of the tooth using intraoral periapical radiograph. Results: There was significant increase in score of gingival index and OHI score for both SSC and zirconia crowns after 3 month followed by reduction in score at 6 and 9 months. There was no statistically significant difference in alveolar bone height in both groups (zirconia and SSCs) for 6 months. Conclusion: Zirconia crowns presented to be an excellent choice for primary posterior teeth full coverage restorations. Zirconia crowns performed better than SSCs in the aspect of gingival response and prevention of plaque adhesion. Keywords: zirconia crowns, stainless steel crown, primary molars, esthetics, dental caries.

Degradable Pure Magnesium Used as a Barrier Film for Oral Bone Regeneration.

The barrier membrane plays an extremely critical role in guided bone regeneration (GBR), which determines the success or failure of GBR technology. In order to obtain barrier membranes with high mechanical strength and degradability, some researchers have focused on degradable magnesium alloys. However, the degradation rate of pure Mg-based materials in body fluids is rather fast, thus posing an urgent problem to be solved in oral clinics. In this study, a novel micro-arc oxidation (MAO) surface-treated pure Mg membrane was prepared. Electrochemical tests, immersion experiments and in vivo experiments were carried out to investigate its potential use as a barrier membrane. The experimental results showed that the corrosion resistance of a pure Mg membrane treated by MAO is better than that of the uncoated pure Mg. The results of cell experiments showed no obvious cytotoxicity, which suggests the enhanced differentiation of osteoblasts. At the same time, the MAO-Mg membrane showed better biological activity than the pure Ti membrane in the early stage of implantation, exhibiting relatively good bone regeneration ability. Consequently, the MAO membrane has been proven to possess good application prospects for guided bone regeneration.

Tobacco Use and Incidence of Adverse Oral Health Outcomes Among US Adults in the Population Assessment of Tobacco and Health Study

Evolving tobacco use patterns, including increasing electronic nicotine delivery systems (ENDS) use, warrant re-examination of the associations between tobacco use and oral health. To examine associations between tobacco product use and incidence of adverse oral health outcomes. This cohort study used nationally representative data from wave (W) 1 to W5 (2013-2019) of the Population Assessment of Tobacco and Health Study. Recruitment used a stratified address-based, area-probability household sample of the noninstitutionalized US civilian population. The W1 cohort included respondents aged 18 years and older without lifetime history of oral health outcomes at W1 or W3, depending on when the outcome was first assessed. Data analysis was performed from October 2021 to September 2022. Current (every day or someday use) established (lifetime use of at least 100 cigarettes or "fairly regular" use of other products) use of cigarettes, ENDS, cigars, pipes, hookah, snus, and smokeless tobacco, excluding snus at W1 to W4. The primary outcomes were past 12-month self-reported diagnosis of gum disease and precancerous oral lesions (W2-W5) and bone loss around teeth, bleeding after brushing or flossing, loose teeth, and 1 or more teeth removed (W4-W5). Sample sizes varied across the 6 oral health outcomes (13 149 respondents for the gum disease sample, 14 993 respondents for the precancerous oral lesions sample, 16 312 respondents for the bone loss around teeth sample, 10 286 respondents for the bleeding after brushing or flossing sample, 15 686 respondents for the loose teeth sample, and 12 061 respondents for the 1 or more teeth removed sample). Slightly more than half of adults (52%-54% across the 6 samples) were women, and the majority were of non-Hispanic White race and ethnicity. Cox proportional hazards models were developed with covariates that included time-dependent tobacco use variables mutually adjusted for each other. Cigarette smoking was positively associated with incidence of gum disease diagnosis (adjusted hazard ratio [AHR], 1.33; 95% CI, 1.11-1.60), loose teeth (AHR, 1.35; 95% CI, 1.05-1.75), and 1 or more teeth removed (AHR, 1.43; 95% CI, 1.18-1.74). Cigar smoking was positively associated with incidence of precancerous oral lesions (AHR, 2.18; 95% CI, 1.38-3.43). In addition, hookah smoking was positively associated with incidence of gum disease diagnosis (AHR, 1.78; 95% CI, 1.20-2.63), and ENDS use was positively associated with incidence of bleeding after brushing or flossing (AHR, 1.27; 95% CI, 1.04-1.54). No associations were observed between snus and smokeless tobacco excluding snus and incidence of oral health outcomes. The observed associations of combustible tobacco use with incidence of several adverse oral health outcomes and ENDS use with incidence of bleeding after brushing or flossing highlight the importance of longitudinal studies and emphasize the continued importance of tobacco cessation counseling and resources in clinical practice.

Mediterranean diet component oleic acid increases protective lipid mediators and improves trabecular bone in a Porphyromonas gingivalis inoculation model.

Therapeutic modulation of bacterial-induced inflammatory host response is being investigated in gingival inflammation and periodontal disease pathology. Therefore, dietary intake of the monounsaturated fatty acid (FA) oleic acid (OA (C18:1)), which is the main component of Mediterranean-style diets, and saturated FA palmitic acid (PA (C16:0)), which is a component of Western-style diets, was investigated for their modifying potential in an oral inoculation model of Porphyromonas gingivalis. Normal-weight C57BL/6-mice received OA- or PA-enriched diets (PA-ED, OA-ED, PA/OA-ED) or normal standard diet for 16 weeks and were inoculated with P. gingivalis/placebo (n=12/group). Gingival inflammation, alveolar bone structure, circulating lipid mediators, and in vitro cellular response were determined. FA treatment of P. gingivalis-lipopolysaccharide-incubated gingival fibroblasts (GFbs) modified inflammatory activation, which only PA exacerbated with concomitant TNF-α stimulation. Mice exhibited no signs of acute inflammation in gingiva or serum and no inoculation- or nutrition-associated changes of the crestal alveolar bone. However, following P. gingivalis inoculation, OA-ED improved oral trabecular bone micro-architecture and enhanced circulating pro-resolving mediators resolvin D4 (RvD4) and 4-hydroxydocosahexaenoic acid (4-HDHA), whereas PA-ED did not. In vitro experiments demonstrated significantly improved differentiation in RvD4- and 4-HDHA-treated primary osteoblast cultures and reduced the expression of osteoclastogenic factors in GF. Further, P. gingivalis infection of OA-ED animals led to a serum composition that suppressed osteoclastic differentiation in vitro. Our results underline the preventive impact of Mediterranean-style OA-EDs by indicating their pro-resolving nature beyond anti-inflammatory properties.

Do silver/hydroxyapatite and zinc oxide nano-coatings improve inflammation around titanium orthodontic mini-screws? In vitro study

Overcoming the failure percentage of orthodontic mini-screws (OMSs), which is about 30% of overall orthodontic cases, especially in malocclusion treatment that requires orthopaedic heavy forces, is a great challenge. Bacterial infections, soft tissue and bone inflammation, and weak connections between bones and the OMS surface are among the main causalities of this failure. The aim of the study is to evaluate in vitro the microbiological activities of the deposited nanomaterials (Silver/hydroxyapatite nanoparticles (Ag/HA NPs) and zinc oxide nanoparticles (ZnO NPs)) in terms of microbial inhibition. In addition, the in-vitro cytotoxicity and cytocompatibility of the synthesized nano-coatings prior to their in-vivo application in animal models were tested on four types of cells, namely, fibroblasts, osteocytes, osteoblasts, and oral epithelial cells. Ag/HA NPs and ZnO NPs were built up onto the surface of titanium OMSs by electrochemical deposition. This electrochemical deposition was performed on 50 orthodontic mini screws and the deposited materials were characterized with the aid of scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX) analysis, X-ray Diffraction (XRD) and nano-scratch test. In addition, the microbiological activities of the deposited nanomaterials were explored in vitro in terms of microbial inhibition. Furthermore, the cytotoxicity and cytocompatibility were tested on four types of cells, namely, fibroblasts, osteocytes, osteoblasts and oral epithelial cells. SEM images revealed spherical Ag NPs in the range of 40-70nm in diameter, rod-shaped HA NPs and porous scaly ZnO NPs on the surface of the OMSs. XRD analysis confirmed the crystal structures of AgNPs, HA NPs, and ZnO NPs. ZnO NPs coated OMS had the highest antimicrobial activity than Ag/HA coated OMS against Gram-positive, Gram-negative and fungal strains. Moreover, after incubation, the decrease in the number of bacterial colonies was significant with ZnO and Ag/HA nanoparticles (with the greatest decrease for the former), due to the potent antibacterial effect of nanoparticles against Escherichia coli and Enterococcus faecalis. Moreover, ZnO NPs-coated OMSs showed a better cytocompatibility with oral epithelium, bone cells, and fibroblasts compared to Ag/HA NPs. The suggested nanocoating is a promising strategy to overcome the development of an inflammatory zone around the fixed OMSs.

In vitro application of drug-loaded hydrogel combined with 3D-printed porous scaffolds

Titanium mesh and three-dimensional titanium alloy scaffolds play a key role in addressing oral and maxillofacial bone defects, which can provide a specific environment and structure for bone growth and development. The two main causes of implant surgery failure are aseptic loosening and bacterial-induced implant-associated infections. To make bone defect implants effective for a long time, the ideal scaffold should take into account the two functions of osseointegration and anti-infection. Therefore, on the basis of the low-elastic-modulus Ti-10Ta-2Nb-2Zr (TTNZ) alloys developed by the research group in the early stage, this study intends to combine the vancomycin-loaded hydrogel with the 3D-printed through-hole porous titanium alloy scaffold to endow 3D-printed TTNZ scaffolds with antibacterial properties. The antibacterial properties of the complex were investigated by the zone of inhibition test and the adhesion/free antibacterial test. The effects of the composite system on osseointegration were investigated from the aspects of cell adhesion, cell proliferation and osteogenesis-related gene expression. The results showed that loading 2.5 wt.% and 5 wt.% vancomycin did not affect the structure of chitosan–hyaluronic acid hydrogel. The properties of the hydrogels were examined by scanning electron microscopy, Fourier-transform infrared, degradation experiment in vitro and vancomycin release experiment in vitro. When combined with porous scaffolds, the drug-loaded hydrogels exhibited slower drug release rates and longer release times. In addition, in vitro studies found that the TTNZ scaffolds loaded with 5 wt.% vancomycin had a certain effect on the expression of osteogenesis-related genes in cells, but the antibacterial effect was the best. The porous scaffolds loaded with 2.5 wt.% vancomycin hydrogel TTNZ scaffolds did not inhibit cell proliferation, adhesion, alkaline phosphatase activity, and osteogenesis-related gene ex-pression, but the antibacterial effect on free bacteria was not as good as that of TTNZ scaffolds loaded with 5 wt.% vancomycin. This study, complementing the advantages of the two and controlling the local release rate of vancomycin, provides a new idea for future 3D printing of titanium alloy stents for anti-infection.

Correction: Macrophage-Specific TLR2 Signaling Mediates Pathogen-Induced TNF-Dependent Inflammatory Oral Bone Loss.

<h3>Abstract</h3> Let-7 is an evolutionary conserved microRNA that mediates post-transcriptional gene silencing to regulate a wide range of biological processes, including development, differentiation, and tumor suppression. Let-7 biogenesis is tightly regulated by several RNA-binding proteins, including Lin28A/B, which represses let-7 maturation. To identify new regulators of let-7, we devised a cell-based functional screen of RNA-binding proteins using a let-7 sensor luciferase reporter, and identified the tRNA pseudouridine synthase, TruB1. TruB1 enhanced maturation specifically of let-7 family members. Rather than inducing pseudouridylation of the miRNAs, HITS-CLIP (High throughput sequencing crosslinking immunoprecipitation) and biochemical analyses revealed direct binding between endogenous TruB1 and the stem-loop structure of pri-let-7, which also binds Lin28A/B. TruB1 selectively enhanced the interaction between pri-let-7 and the microprocessor DGCR-8, which mediates miRNA maturation. Finally, TruB1 suppressed cell proliferation, which was mediated in part by let-7. Altogether, we reveal an unexpected function for TruB1 in promoting let-7 maturation and function.

Regulation of LL-37 in Bone and Periodontium Regeneration.

The goal of regenerative therapy is to restore the structure and function of the lost tissues in the fields of medicine and dentistry. However, there are some challenges in regeneration therapy such as the delivery of oxygen and nutrition, and the risk of infection in conditions such as periodontitis, osteomyelitis, etc. Leucine leucine-37 (LL-37) is a 37-residue, amphipathic, and helical peptide found only in humans and is expressed throughout the body. It has been shown to induce neovascularization and vascular endothelial growth factor (VEGF) expression. LL-37 also stimulates the migration and differentiation of mesenchymal stem cells (MSCs). Recent studies have shown that LL-37 plays an important role in the innate defense system through the elimination of pathogenic microbes and the modulation of the host immune response. LL-37 also manifests other functions such as promoting wound healing, angiogenesis, cell differentiation, and modulating apoptosis. This review summarizes the current studies on the structure, expression, and function of LL-37 and highlights the contributions of LL-37 to oral cavity, periodontium, and bone regeneration.

A matter of origin - identification of SEMA3A, BGLAP, SPP1 and PHEX as distinctive molecular features between bone site-specific human osteoblasts on transcription level.

In oral and maxillofacial bone reconstruction, autografts from the iliac crest represent the gold standard due to their superior clinical performance, compared to autografts derived from other extraoral regions. Thus, the aim of our study was to identify putative differences between osteoblasts derived from alveolar (hOB-A) and iliac crest (hOB-IC) bone of the same donor (nine donors) by means of their molecular properties in 2D and 3D culture. We thereby focused on the gene expression of biomarkers involved in osteogenic differentiation, matrix formation and osteoclast modulation. Furthermore, we examined the transcriptional response to Vit.D3 in hOB-A and hOB-IC. Our results revealed different modulation modes of the biomarker expression in osteoblasts, namely cell origin/bone entity-dependent, and culture configuration- and/or time-dependent modulations. SEMA3A, SPP1, BGLAP and PHEX demonstrated the strongest dependence on cell origin. With respect to Vit.D3-effects, BGLAP, SPP1 and ALPL displayed the highest Vit.D3-responsiveness. In this context we demonstrated that the transcriptional Vit.D3-response concerning SPP1 and ALPL in human osteoblasts depended on the cell origin. The results indicate a higher bone remodeling activity of iliac crest than alveolar osteoblasts and support the growing evidence that a high osteoclast activity at the host-/donor bone interface may support graft integration.

N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging

BackgroundDental follicle stem cells (DFSCs) show mesenchymal stem cell properties with the potential for alveolar bone regeneration. Stem cell properties can be impaired by reactive oxygen species (ROS), prompting us to examine the importance of scavenging ROS for stem cell-based tissue regeneration. This study aimed to investigate the effect and mechanism of N-acetylcysteine (NAC), a promising antioxidant, on the properties of DFSCs and DFSC-based alveolar bone regeneration.MethodsDFSCs were cultured in media supplemented with different concentrations of NAC (0–10 mM). Cytologic experiments, RNA-sequencing and antioxidant assays were performed in vitro in human DFSCs (hDFSCs). Rat maxillary first molar extraction models were constructed, histological and radiological examinations were performed at day 7 post-surgery to investigate alveolar bone regeneration in tooth extraction sockets after local transplantation of NAC, rat DFSCs (rDFSCs) or NAC-treated rDFSCs.Results5 mM NAC-treated hDFSCs exhibited better proliferation, less senescent rate, higher stem cell-specific marker and immune-related factor expression with the strongest osteogenic differentiation; other concentrations were also beneficial for maintaining stem cell properties. RNA-sequencing identified 803 differentially expressed genes between hDFSCs with and without 5 mM NAC. “Developmental process (GO:0032502)” was prominent, bioinformatic analysis of 394 involved genes revealed functional and pathway enrichment of ossification and PI3K/AKT pathway, respectively. Furthermore, after NAC treatment, the reduction of ROS levels (ROS, superoxide, hydrogen peroxide), the induction of antioxidant levels (glutathione, catalase, superoxide dismutase), the upregulation of PI3K/AKT signaling (PI3K-p110, PI3K-p85, AKT, phosphorylated-PI3K-p85, phosphorylated-AKT) and the rebound of ROS level upon PI3K/AKT inhibition were showed. Local transplantation of NAC, rDFSCs or NAC-treated rDFSCs was safe and promoted oral socket bone formation after tooth extraction, with application of NAC-treated rDFSCs possessing the best effect.ConclusionsThe proper concentration of NAC enhances DFSC properties, especially osteogenesis, via PI3K/AKT/ROS signaling, and offers clinical potential for stem cell-based alveolar bone regeneration.

Polysaccharide Based Implantable Drug Delivery: Development Strategies, Regulatory Requirements, and Future Perspectives

Implantable drug delivery systems advocate a wide array of potential benefits, including effective administration of drugs at lower concentrations and fewer side-effects whilst increasing patient compliance. Amongst several polymers used for fabricating implants, biopolymers such as polysaccharides are known for modulating drug delivery attributes as desired. The review describes the strategies employed for the development of polysaccharide-based implants. A comprehensive understanding of several polysaccharide polymers such as starch, cellulose, alginate, chitosan, pullulan, carrageenan, dextran, hyaluronic acid, agar, pectin, gellan gum is presented. Moreover, biomedical applications of these polysaccharide-based implantable devices along with the recent advancements carried out in the development of these systems have been mentioned. Implants for the oral cavity, nasal cavity, bone, ocular use, and antiviral therapy have been discussed in detail. The regulatory considerations with respect to implantable drug delivery has also been emphasized in the present work. This article aims to provide insights into the developmental strategies for polysaccharide-based implants.

Botanicals and Oral Stem Cell Mediated Regeneration: A Paradigm Shift from Artificial to Biological Replacement.

Stem cells are a well-known autologous pluripotent cell source, having excellent potential to develop into specialized cells, such as brain, skin, and bone marrow cells. The oral cavity is reported to be a rich source of multiple types of oral stem cells, including the dental pulp, mucosal soft tissues, periodontal ligament, and apical papilla. Oral stem cells were useful for both the regeneration of soft tissue components in the dental pulp and mineralized structure regeneration, such as bone or dentin, and can be a viable substitute for traditionally used bone marrow stem cells. In recent years, several studies have reported that plant extracts or compounds promoted the proliferation, differentiation, and survival of different oral stem cells. This review is carried out by following the PRISMA guidelines and focusing mainly on the effects of bioactive compounds on oral stem cell-mediated dental, bone, and neural regeneration. It is observed that in recent years studies were mainly focused on the utilization of oral stem cell-mediated regeneration of bone or dental mesenchymal cells, however, the utility of bioactive compounds on oral stem cell-mediated regeneration requires additional assessment beyond in vitro and in vivo studies, and requires more randomized clinical trials and case studies.

Spheroid co-culture of BMSCs with osteocytes yields ring-shaped bone-like tissue that enhances alveolar bone regeneration

Oral and maxillofacial bone defects severely impair appearance and function, and bioactive materials are urgently needed for bone regeneration. Here, we spheroid co-cultured green fluorescent protein (GFP)-labeled bone marrow stromal cells (BMSCs) and osteocyte-like MLO-Y4 cells in different ratios (3:1, 2:1, 1:1, 1:2, 1:3) or as monoculture. Bone-like tissue was formed in the 3:1, 2:1, and 1:1 co-cultures and MLO-Y4 monoculture. We found a continuous dense calcium phosphate structure and spherical calcium phosphate similar to mouse femur with the 3:1, 2:1, and 1:1 co-cultures, along with GFP-positive osteocyte-like cells encircled by an osteoid-like matrix similar to cortical bone. Flake-like calcium phosphate, which is more mature than spherical calcium phosphate, was found with the 3:1 and 2:1 co-cultures. Phosphorus and calcium signals were highest with 3:1 co-culture, and this bone-like tissue was ring-shaped. In a murine tooth extraction model, implantation of the ring-shaped bone-like tissue yielded more bone mass, osteoid and mineralized bone, and collagen versus no implantation. This tissue fabricated by spheroid co-culturing BMSCs with osteocytes yields an internal structure and mineral composition similar to mouse femur and could promote bone formation and maturation, accelerating regeneration. These findings open the way to new strategies in bone tissue engineering.

Alendronate modified mPEG-PLGA nano-micelle drug delivery system loaded with astragaloside has anti-osteoporotic effect in rats

Astragaloside (AS) has an anti-osteoporotic effect, but its poor water solubility and low bioavailability limit its application. In this study, a novel nano-carrier with bone targeting was prepared by modifying mPEG-PLGA with alendronate (AL) before incorporation into astragaloside nano-micelles (AS-AL-mPEG-PLGA) to enhance the oral bioavailability, bone targeting and anti-osteoporosis effect of AS. The release behavior of AS-AL-mPEG-PLGA in vitro was investigated via dialysis. The pharmacokinetics of AS-AL-mPEG-PLGA was studied in Sprague-Dawley (SD) rats. The cytotoxicity of AS-AL-mPEG-PLGA in vitro (via MTT method), coupled with bone targeting ability in vitro and in vivo were evaluated. The therapeutic effects of free AS and AS-AL-mPEG-PLGA (ELISA, micro-CT, H&E staining) were compared in osteoporotic rats. AS-AL-mPEG-PLGA with smaller particle size (45.3 ± 3.8 nm) and high absolute zeta potential (−23.02 ± 0.51 mV) were successfully prepared, wherein it demonstrated higher entrapment efficiency (96.16 ± 0.18%), a significant sustained-release effect for 96 h and acceptable safety within 10–200 μg/mL. AS-AL-mPEG-PLGA could enhance the hydroxyapatite affinity and bone tissue concentration of AS. The relative bioavailability of AS-AL-mPEG-PLGA was 233.90% compared with free AS. In addition, the effect of AS in reducing serum levels of bone metabolism-related indicators, restoring the bone microarchitecture and improving bone injury could be enhanced by AS-AL-mPEG-PLGA. AS-AL-mPEG-PLGA with small particle size, good stability, remarkable sustained-release effect, safety and bone targeting was successfully constructed in this experiment to potentially improve the oral bioavailability and anti-osteoporosis effect of AS. Thus, AS-AL-mPEG-PLGA may be a promising strategy to prevent and treat osteoporosis.

Locally Applied Repositioned Hormones for Oral Bone and Periodontal Tissue Engineering: A Narrative Review.

Bone and periodontium are tissues that have a unique capacity to repair from harm. However, replacing or regrowing missing tissues is not always effective, and it becomes more difficult as the defect grows larger. Because of aging and the increased prevalence of debilitating disorders such as diabetes, there is a considerable increase in demand for orthopedic and periodontal surgical operations, and successful techniques for tissue regeneration are still required. Even with significant limitations, such as quantity and the need for a donor area, autogenous bone grafts remain the best solution. Topical administration methods integrate osteoconductive biomaterial and osteoinductive chemicals as hormones as alternative options. This is a promising method for removing the need for autogenous bone transplantation. Furthermore, despite enormous investigation, there is currently no single approach that can reproduce all the physiologic activities of autogenous bone transplants. The localized bioengineering technique uses biomaterials to administer different hormones to capitalize on the host’s regeneration capacity and capability, as well as resemble intrinsic therapy. The current study adds to the comprehension of the principle of hormone redirection and its local administration in both bone and periodontal tissue engineering.

Extracellular vesicles derived from human dental mesenchymal stem cells stimulated with low-intensity pulsed ultrasound alleviate inflammation-induced bone loss in a mouse model of periodontitis

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have emerged as a new mode of intercellular crosstalk and are responsible for many of the therapeutic effects of MSCs. To promote the application of MSC-EVs, recent studies have focused on the manipulation of MSCs to improve the production of EVs and EV-mediated activities. The current paper details an optimization method using non-invasive low-intensity pulsed ultrasound (LIPUS) as the stimulation for improving oral MSC-EV production and effectiveness. Stem cells from apical papilla (SCAP), a type of oral mesenchymal stem cell, displayed intensity-dependent pro-osteogenic and anti-inflammatory responses to LIPUS without significant cytotoxicity or apoptosis. The stimuli increased the secretion of EVs by promoting the expression of neutral sphingomyelinases in SCAP. In addition, EVs from LIPUS-induced SCAP exhibited stronger efficacy in promoting the osteogenic differentiation and anti-inflammation of periodontal ligament cells in vitro and alleviating oral inflammatory bone loss in vivo. In addition, LIPUS stimulation affected the physical characteristics and miRNA cargo of SCAP-EVs. Further investigations indicated that miR-935 is an important mediator of the pro-osteogenic and anti-inflammatory capabilities of LIPUS-induced SCAP-EVs. Taken together, these findings demonstrate that LIPUS is a simple and effective physical method to optimize SCAP-EV production and efficacy.

Spatiotemporal self-strengthening hydrogels for oral tissue regeneration

As the forefront of the digestive system, a mouth in a high moist microenvironment is easy to breed bacteria and the inevitable injury from oral surgeries will cause a series of physiological disorders. The injectable hydrogels are promising biomaterials to solve this challenge, but the limited mechanical performance and weak mechanical adjustment are insufficient to fit in the whole healing process. Herein, we propose and design a new spatiotemporal self-strengthening injectable hydrogel via manipulating the time-dependent cross-linking effects after the Schiff base reaction. The resultant hydrogels possess various promising properties and functions, including rapid initial gelation efficiency (∼30 s), spatiotemporal adjustable mechanical strength, great antifouling property and biocompatibility, leading to effective promote oral tissue regeneration and bone repair. We believe both our concept and spatiotemporal self-strengthening injectable hydrogels will provide new insight into the hydrogel-based wound dressing and broaden the application of the bioinspired hydrogels in biomedical fields.

Autogenous Bone is Still the Gold Standard of Graft Materials in 2022.

I read with interest the recent editorial entitled “Is Autogenous Bone Grafting Still the “Gold Standard” in Oral Bone Grafting?”.1 As the authors pointed out, I wrote a similar editorial in 2010 and concluded that indeed autogenous bone was the gold standard of graft materials.2 However, the authors have challenged my conclusion. To support their opinion, they referenced two publications on sinus bone grafting evaluating histomorphometric results and implant survival.3,4 They claimed these studies found that “bone substitutes either performed in a like manner or superior to autogenous bone alone”. However, the histomorphometric analysis showed autogenous bone resulted in the highest amount of new bone formation compared to bone substitutes, but bone substitutes seem to be a good alternative.3 The systematic review on sinus bone grafting concluded implant survival rates using bone substitutes were as effective as autogenous bone when used alone or in combination with autogenous bone.4 Although the implant survival was lower with 100% autogenous bone (87.7%) compared to autograft with bone substitutes (94.9%) or bone substitutes alone (96%), the data clearly shows that the majority of machined implants were placed in sinuses grafted with autogenous bone. The review found rough surface implants had superior survival rates compared to machined implants (96% vs. 85.6%), so this explains the lower implant survival rate in autogenous grafts. Pjetursson et al5 performed a systematic review evaluated the grafting of pneumatized sinuses that had 6.0 mm or less residual bone height. Focusing on outcomes using only rough surface implants they found high implant survival rates for all types of grafts (> 96%). However, rough implants placed in particulate autogenous bone had a significantly higher estimated three-year survival (99.8%). There are limitations in using a secondary outcome measure, such as implant survival, to evaluate graft success. The assumption is that if the implant survived the graft was successful. The influence of the amount of native bone supporting the implant is unknown in some studies unless the residual bone limit was defined, such as in the Pjetursson et al study.Another important distinction is the relationship of the augmentation to the osseous defect. Bone defects inside the bony contour, such as sockets and the maxillary sinus floor, are much easier and predictable to reconstruct than horizontal and vertical augmentation outside the bone contour. Intrabony defects have a greater number of bone walls with a higher regenerative capacity. There is also greater ease in achieving soft tissue coverage, space maintenance, graft stability and protection. As such bone substitutes perform well in treating these types of contained defects. However, horizontal and vertical bone augmentation outside the bone contour is more biologically challenging. The greater the distance from the native bone, the more difficult it may become for vascular ingrowth, cell migration and bone formation at the outer limits of the graft. As such a graft material with greater regenerative capacity may be needed to obtain the required bone gains. Autogenous bone has superior biologic qualities compared to osteoconductive bone substitutes. It is the only bone graft material that fulfills all three aspects of the tissue engineering triad - osteogenesis, osteoinduction and osteoconduction. Autogenous bone contains osteocompetent cells and osteoconductive growth factors that can positively influence bone formation. Although cancellous bone contains a higher amount of osteoblasts and mesenchymal stem cells, cortical bone grafts contain cells that have the ability to proliferate and differentiate into the osteogenic lineage, suggesting that these cells can also contribute to bone regeneration following transplantation.6 Research has found cortical bone chips contain over 40 different growth factors that can modulate the cellular aspects of bone regeneration.7 The healing time of autogenous bone grafts also is shorter than bone substitutes.8Rather than focus on implant survival, it would be more clinically relevant to evaluate horizontal and vertical bone gains produced by different graft materials. When reviewing studies measuring bone gains it becomes evident that autogenous bone is needed for larger bone augmentations and vertical gains.9,10,11,12 While I agree with my colleagues that bone substitutes may be used effectively in many clinical situations, I still maintain that autogenous bone is the gold standard of graft materials. This does not mean it is the first choice option, but it does offer biologic advantages unmatched by bone substitutes. The use of a local donor site and bone scrapers can decrease the morbidity of bone harvest. In addition, some donor sites for block grafting, such as the mandibular ramus, have a lower incidence of postoperative complications.13 Surgeons should weigh the advantages and disadvantages of each material and select an approach that has the highest likelihood of clinical success.14