Search Results (1,174)

Background: Patients with a thin gingival phenotype and a narrow buccal alveolar plate are highly susceptible to periodontal complications during orthodontic expansion. Traditional biomechanics often fail to maintain root control in thin alveolar housing. This report presents two clinical cases illustrating soft- and hard-tissue responses to a novel biomechanical approach, the Bone Protection System (BPS), designed to reduce buccal cortical overload during expansion. Case Presentation: Two adult patients with a thin gingival phenotype assessed by a standardized periodontal probe transparency test and narrow alveolar ridges underwent orthodontic expansion. Patient 1 was treated with the full BPS protocol in both arches. Patient 2 received BPS only in the maxilla, while the mandible was treated conventionally, creating an intra-individual control model under identical systemic conditions. Soft-tissue phenotype and cortical plate response were evaluated clinically and radiographically when applicable. Results: In Patient 1 clinically, the vestibular phenotype showed clear thickening and stabilization. In Patient 2, the maxillary arch treated with BPS exhibited progressive thickening of the vestibular phenotype, whereas the mandible treated conventionally presented thinning and increased translucency—features consistent with buccal compression in thin alveolar bone. No soft- or hard-tissue augmentation procedures were performed in either case. Conclusions: The Bone Protection System may contribute to improved periodontal safety during orthodontic expansion in thin-biotype patients by reducing buccal cortical loading and supporting adaptive soft-tissue and bone responses. Preliminary observations suggests that BPS has potential value for possibly expanding the biological limits of safe tooth movement. Further studies on larger cohorts are warranted. Full article

Background and Objectives: This study aims to analyze the effects of levetiracetam (LEV) and valproic acid (VPA) administration on oxidative stress, inflammation, apoptosis, extracellular matrix dynamics, and bone remodeling parameters in rat alveolar bone exposed to orthodontic force. Materials and Methods: Four experimental groups were designed for this study: Control, Force, Force + LEV, and Force + VPA. LEV (150 mg/kg/day) or VPA (300 mg/kg/day) was administered intraperitoneally to the experimental groups daily for 6 weeks. At the end of the experimental period, the alveolar bone tissues were used for molecular analyses. RT-PCR analysis was performed to assess the expression levels of antioxidant markers [superoxide dismutase, (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH)], inflammatory cytokines [tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)], apoptosis-related genes (Bax, Bcl-2, and Caspase-3), matrix remodeling genes [matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and metallopeptidase inhibitor 1 (TIMP-1)], and bone metabolism regulators [receptor activator of nuclear factor kappa-Β ligand (RANKL) and osteoprotegerin (OPG)]. Oxidative stress and inflammatory measurements were also confirmed via ELISA assays. Results: The results demonstrated that orthodontic force application increased oxidative stress, inflammation, and apoptosis compared to the Control group, disrupted extracellular matrix homeostasis, and increased bone resorption, while LEV administration (LEV + Force) markedly mitigated these abnormalities. In other words, LEV administration increased levels of antioxidant markers, decreased levels of inflammatory cytokines and pro-apoptotic genes, restored extracellular matrix balance (decrease in MMP-2 and MMP-9 with concurrent upregulation of TIMP-1), and limited tissue destruction (decrease in RANKL along with elevation in OPG). In contrast to LEV, VPA did not correct these molecular alterations induced by orthodontic force and, in several parameters, further exacerbated them. Conclusions: In conclusion, molecular data from the animal model indicate that LEV plays a protective role against orthodontic force by reducing excess levels of oxidative stress, apoptosis, and inflammation and homeostatic pathways. Full article

Background: Mechanical loading is a fundamental regulator of bone remodelling; however, the mechanotransduction mechanisms governing alveolar bone adaptation under tensile-dominant orthodontic loading remain insufficiently defined. In particular, the molecular pathways associated with tension-driven cortical modelling in the periodontal ligament (PDL)–bone complex have not been systematically interpreted in the context of advanced biomechanical simulations. Methods: A nonlinear finite element model of the alveolar bone–PDL–tooth complex was developed using patient-specific CBCT data. Three loading configurations were analysed: (i) conventional orthodontic loading, (ii) loading combined with corticotomy alone, and (iii) a translation-dominant configuration generated by the Bone Protection System (BPS). Pressure distribution, displacement vectors, and stress polarity within the PDL and cortical plate were quantified across different bone density conditions. The mechanical outputs were subsequently interpreted in relation to established mechanotransductive molecular pathways involved in osteogenesis and angiogenesis. Results: Conventional loading generated compression-dominant stress fields within the marginal PDL, frequently exceeding physiological thresholds and producing moment-driven root displacement. Corticotomy alone reduced local stiffness but did not substantially alter stress polarity. The BPS configuration redirected loads toward a tensile-favourable mechanical environment characterised by reduced peak compressive pressures and parallel (translation-dominant) displacement vectors. The predicted tensile stress distribution is compatible with activation profiles of key mechanosensitive pathways, including integrin–FAK signalling, Wnt/β-catenin–mediated osteogenic differentiation and HIF-1α/VEGF-driven angiogenic coupling, suggesting a microenvironment that may be more conducive to cortical apposition than to resorption. Conclusions: This study presents a computational–molecular framework linking finite element–derived tensile stress patterns with osteogenic and angiogenic signalling pathways relevant to alveolar bone remodelling. The findings suggestthat controlled redirection of orthodontic loading toward tensile domains may shift the mechanical environment of the PDL–bone complex toward conditions associated with osteogenic than resorptive responses providing a mechanistic basis for tension-induced cortical modelling. This mechanobiological paradigm advances the understanding of load-guided alveolar bone adaptation at both the tissue and molecular levels. Full article

Understanding how primary structural features and secondary material properties adapt to functional loads is essential to determining their effect on changes in joint biomechanics over time. The objective of this study was to map and correlate spatiotemporal changes in primary structural features, secondary material properties, and dentoalveolar joint (DAJ) stiffness with age in rats subjected to prolonged chewing of soft foods versus hard foods. To probe how loading history shapes the balance between the primary and secondary features, four-week-old rats were fed either a hard-food (HF, N = 25) or soft-food (SF, N = 25) diet for 4, 12, 16, and 20 weeks, and functional imaging of intact mandibular DAJs was performed at 8, 12, 16, 20, and 24 weeks. Across this time course, the primary structural determinants of joint function (periodontal ligament (PDL) space, contact area, and alveolar bone socket morphology) and secondary material and microstructural determinants (tissue-level stiffness encoded by bone and cementum volume fractions, pore architecture, and bone microarchitecture) were quantified. As the joints matured, bone and cementum volume fractions increased in both the HF and SF groups but along significantly different trajectories, and these changes correlated with a pronounced decrease in PDL-space from 12 to 16 weeks in both diets. With further aging, older HF rats maintained significantly wider PDL-spaces than SF rats. These evolving physical features were accompanied by an age-dependent significant increase in the contact ratio in the SF group. The DAJ stiffness was significantly greater in SF than HF animals at younger ages, indicating that food hardness-dependent remodeling alters the relative contribution of structural versus material factors to joint function across the life course. At the tissue level, volumetric strains, representing overall volume changes, and von Mises bone strains, representing shape changes, increased with age in HF and SF joints, with volumetric strain rising rapidly from 16 to 20 weeks and von Mises strain increasing sharply from 12 to 16 weeks. Bone in SF animals exhibited higher and more variable strain values than age-matched HF bone, and changes in joint space, degrees of freedom, contact area, and bone strain correlated with joint biomechanics, demonstrating that multiscale functional biomechanics, including bone strain in intact DAJs, are colocalized with anatomy-specific physical effectors. Together, these spatiotemporal shifts in primary (structure/form), and secondary features (material properties and microarchitecture) define divergent mechanobiological pathways for the DAJ and suggest that altered loading histories can bias joints toward early maladaptation and potential degeneration. Full article

Extracellular vesicle (EV)-based therapies have emerged as promising, cell-free approaches for dental tissue regeneration. This narrative review integrates mechanistic insights, therapeutic efficacy data, and safety and delivery considerations from in vitro and in vivo studies to elucidate the molecular mechanisms by which EVs, particularly those from dental pulp stem cells (DPSCs) and mesenchymal stem cells (MSCs), drive regenerative processes via key signalling axes (PI3K/Akt, MAPK, BMP/Smad, and Hedgehog). Preclinical studies demonstrate that unmodified and engineered EVs enhance odontogenic differentiation, angiogenesis, bone repair, and immunomodulation in models of pulp regeneration, alveolar bone defects, osteonecrosis, and periodontitis. Isolation and purification methodologies were also evaluated, comparing ultracentrifugation, size-exclusion chromatography, and density-cushion approaches, and discussing how protocol variations affect EV purity, dosing metrics, and functional reproducibility. Early-phase clinical evaluations report only low-grade transient adverse events, underscoring a generally favourable safety profile. Despite these encouraging results, significant challenges remain: heterogeneity in EV cargo composition, lack of standardised potency assays, and incomplete long-term safety data. The review highlights the urgent need for rigorous, harmonised regulatory frameworks and robust quality control measures to ensure that EV-based modalities can be translated into safe, effective, and reproducible therapies in regenerative dentistry. Full article

Bone tissue engineering, as an important branch of regenerative medicine, integrates multidisciplinary knowledge from cell biology, materials science, and biomechanics, aiming to develop novel biomaterials and technologies for functional repair and regeneration of bone tissue. Hydrogels are among the most commonly used scaffold materials; however, conventional hydrogels exhibit significant limitations in physical properties such as strength, tensile strength, toughness, and fatigue resistance, which severely restrict their application in load-bearing bone defect repair. As a result, the development of high-strength hydrogels has become a research hotspot in the field of bone tissue engineering. This paper systematically reviews the latest research progress in this area: First, it delves into the physicochemical characteristics of high-strength hydrogels at the molecular level, focusing on core features such as their crosslinking network structure, dynamic bonding mechanisms, and energy dissipation principles. Next, it categorically summarizes novel high-strength hydrogel systems and different types of biomimetic hydrogels developed based on various reinforcement strategies. Furthermore, it provides a detailed evaluation of the application effects of these advanced materials in specific anatomical sites, including cranial reconstruction, femoral repair, alveolar bone regeneration, and articular cartilage repair. This review aims to provide systematic theoretical guidance and technical references for the basic research and clinical translation of high-strength hydrogels in bone tissue engineering, promoting the effective translation of this field from laboratory research to clinical application. Full article

Background: Extended platelet-rich fibrin (e-PRF) membranes are a novel 100% autologous biomaterial with a longer resorption time (4–6 months) than traditional solid-PRF membranes (two weeks). In part 1 of this 2-part publication series, four clinical variations for using these novel e-PRF membranes for socket preservation were introduced. In this randomized clinical trial (RCT), all four iterations of e-PRF membranes were compared to traditional collagen membranes in alveolar ridge preservation for hard and soft tissue dimensional changes and early wound healing outcomes. Methods: A single-center RCT was conducted, including 55 patients requiring the extraction of a single tooth with planned implant placement. All sockets were grafted with a “sticky bone” (bone allograft mixed with PRF) and secured with either a collagen membrane (control) or e-PRF membranes utilizing the four variations present in Part 1 (both formed extra-orally or intra-orally, each with or without an overlying solid PRF membrane). The time of fabrication and application of each e-PRF iteration was recorded. Cone beam computed tomography was utilized to evaluate horizontal and vertical ridge dimensions at baseline and 3 months post-operatively, and soft tissue thickness was also measured at both time intervals utilizing an endodontic reamer. Early wound healing was recorded at 2 weeks, utilizing the Landry, Turnbull, and Howley Index by three blinded clinicians. Results: The results demonstrated that, at 3 months, the e-PRF membranes fabricated utilizing all 4 treatment variations demonstrated equal improvements in horizontal and vertical ridge dimensions and soft tissue thickness when compared to collagen membranes. Additionally, the membrane (p = 0.029) and membrane w/solid (p = 0.021) groups demonstrated statistically significant superior early wound healing compared to the collagen membrane group. Notably, the Bio-Filler groups demonstrated statistically significant reduction in fabrication/application time compared to the membrane groups. Conclusions: Within the limitations of this RCT, all e-PRF iterations performed comparably to collagen membranes in maintaining both hard and soft tissue ridge dimensions when combined with sticky bone, while also significantly improving soft tissue wound healing. Future RCTs with alternative grafting materials, direct wound-margin assessment, and evaluation of patient-reported outcomes are necessary to clarify the advantages of each membrane type. Full article

Background/Objectives: Autologous dentin matrix (ADM) has been suggested as a biologically plausible biomaterial for alveolar bone regeneration after tooth extraction. However, clinical evidence regarding its biological activity and early healing outcomes is limited. This exploratory, randomized controlled pilot study aimed to descriptively assess early alveolar healing patterns and bone morphogenetic protein 4 (BMP4) expression following tooth extraction using ADM compared with other grafting approaches. Methods: Patients requiring tooth extraction were allocated to one of four groups: ADM, xenograft, ADM combined with platelet-rich fibrin, and a graft-free control group. Histological and immunohistochemical analyses were performed four months after extraction to descriptively assess cellular features of healing and BMP4 expression. The trial was registered at the Brazilian Registry of Clinical Trials (ReBEC; RBR-24mdgrf) and conducted under prior ethics committee approval. Results: BMP4 expression was detected in 67.9% of the analyzed histological fields, predominantly localized in osteocytic, osteoblastic, and medullary areas. Although descriptive differences in BMP4-positive fields were observed among the groups, no statistically significant differences were identified between the groups. Histological evaluation revealed an active cellular environment across all treatment modalities, consistent with early post-extraction healing. No adverse events related to surgical procedures or grafting materials were reported during the study period. Conclusions: Within the limitations of this pilot randomized clinical trial, ADM exhibited consistent biological behavior during early post-extraction alveolar healing. The observed BMP4 expression likely reflects a general physiological healing response rather than a material-specific effect. This finding supports the biological plausibility of dentin-derived grafts as osteoconductive biomaterials. These findings are hypothesis-generating, and larger, adequately powered randomized clinical trials with standardized molecular and histological assessments are required to determine their clinical relevance. Full article

Periodontitis is a chronic non-communicable inflammatory disease in which oxidative stress plays an important role in tissue destruction and alveolar bone loss. Excessive production of reactive oxygen species disrupts redox homeostasis, activates inflammatory signaling pathways, and promotes regulated cell death processes such as pyroptosis and ferroptosis. The Nrf2/Keap1 pathway is a key regulator of antioxidant defense and cellular adaptation to redox imbalance. Impaired Nrf2 signaling has been associated with enhanced oxidative injury, NF-κB and NLRP3 inflammasome activation, osteoclast-driven bone resorption, and reduced regenerative capacity in periodontal tissues. Experimental studies suggest that Nrf2 activation can restore the redox balance and attenuate inflammation and bone destructive responses in a periodontal model. Moreover, therapeutic approaches involving phytochemicals, microbial-derived metabolites, and redox-responsive biomaterials have been reported to influence Nrf2-related signaling in experimental settings. However, the majority of the available evidence is derived from in vitro or animal studies, and the relevance of these findings to clinical periodontitis remains to be established. This review summarizes the current advances linking oxidative stress, redox signaling, cell death pathways, and bone remodeling with Nrf2 dysfunction in periodontitis and outlines the key mechanistic insights while highlighting the existing knowledge gaps. Full article

Background and Objectives: Periodontal disease, characterized by progressive destruction of tooth-supporting tissues, often results in substantial alveolar bone loss, necessitating regenerative interventions such as guided bone regeneration (GBR). Insulin-like growth factor 2 (IGF-2) has emerged as a promising biomolecule for periodontal regeneration because of its osteogenic and immunomodulatory properties. Materials and Methods: A comprehensive literature search was conducted across five electronic databases (Scopus, ScienceDirect, PubMed, Wiley, and EBSCO). Studies examining the use of IGF-2 in periodontal or alveolar bone regeneration, including randomized controlled trials, animal studies, and in vitro experiments, were included. Results: Three studies met the inclusion criteria. In vitro, IGF-2 was associated with enhanced osteogenic differentiation and mineralization of mesenchymal stem cells, along with upregulation of key osteogenic markers. In animal models, IGF-2 treatment was associated with increased osteogenesis, greater bone volume, and a shift in macrophage polarization toward a less inflammatory phenotype. However, heterogeneity in study designs, protocols, and outcome measures limited direct comparisons. Conclusions: In vitro, IGF-2 was associated with enhanced osteogenic differentiation and mineralization of mesenchymal stem cells, accompanied by upregulation of key osteogenic markers. In animal models, IGF-2 treatment was associated with increased osteogenesis, greater bone volume, and a shift in macrophage polarization toward a less inflammatory phenotype. Full article

Background: Several minimally invasive techniques have been introduced to augment horizontal ridge volume for prosthetically driven implant placement, utilizing different biomaterials to enhance regenerative outcomes. This article presents two clinical cases illustrating a tunneling approach for horizontal alveolar ridge augmentation using a combination of xenogeneic bone graft, hyaluronic acid, and an acellular dermal matrix. Methods: A single vertical incision was made mesial to the bone defect and a dermal matrix was suitably shaped and positioned into the subperiosteal tunnel. Subsequently, the bone graft was inserted between the dermal matrix and the buccal bone plate. Primary wound closure was achieved. After six months, implants were placed. For each patient, an optical scan was performed at baseline (T₀), at six months post-operative ridge augmentation surgery (T₁) and at two months post-implant insertion (T₂). A digital measurement of the horizontal ridge thickness was performed at each inserted implant site. Clinical parameters and patient postoperative morbidity were recorded. Results: The procedure was well tolerated by the patients. No postoperative clinical complications were observed. The mean tissue thickness achieved at T1 was recorded to be 13.3 mm. The same value was recorded at T2. Conclusions: This technique allowed the placement of prosthetically guided implants, with minimal morbidity and no observed complications. Further studies analyzing the histology of newly formed bone and performing three-dimensional radiological examinations to confirm the effectiveness of the surgical technique are warranted to validate these preliminary findings. Clinical Trial Number (NIH): NCT06424223 Full article

Background: Alveolar ridge preservation (ARP) techniques have evolved with implantology development. In clinical practice, biomaterials for ARP are tested in laboratory animals, and rat calvaria is a standard option. The study aimed to evaluate biomaterial osteointegration in defects created in the rat calvaria, comparing an experimental synthetic biomaterial with a bovine xenograft and natural healing. Methods: The study included six groups of animals: two negative control groups with natural healing (2 months (M) and 4 M), two positive control groups with bovine xenograft (2 M and 4 M), and two study groups with nanohydroxyapatite titanium reinforced (2M and 4M). After creating and grafting the defects, healing was expected to take 2 or 4 months, after which bone fragments were harvested, prepared, and then analyzed. OCT, stereomicroscopy, and histology techniques were used for bone fragments analysis, and the obtained images were evaluated using Image J 1.54p software. Results: The results obtained from the three analyses provided information about the healing pattern of bone defects and the degree of new bone formation. Histological analysis of the samples confirmed what the stereomicroscopy and OCT images showed: that the bovine xenograft elicited a better tissue response than the synthetic biomaterial, being incorporated into the bone tissue more than the synthetic biomaterial. Conclusions: Both the bovine xenograft and the synthetic nanocomposite based on hydroxyapatite reinforced with titanium particles favored bone healing, but their integration into the bone was limited for the analyzed period. Full article

Background and Objectives: The insertion of endosseous implants requires the alveolar bone to be drilled, which produces alterations of the osseous neoalveolus approximately 1 mm deep, an area that will later be subjected to osseous renewal. The healing of the bone around the inserted implant is complex and depends on numerous factors, amongst which the size of the insertion orifice relative to the diameter of the implant, the design, and the pace and depth of the threads play an essential part. Therefore, the aim of this paper is to investigate from a histologic point of view the osseointegration of the implants inserted in a rabbit cortical bone by creating a 150 µm high healing chamber. Materials and Methods: 5 mm-long and 2 mm-wide titan implants were inserted into the femur of 15 12-month-old rabbits by using a drill with a 1.8 mm diameter, obtaining a spiralled healing chamber 150 µm high. The animals were euthanized after 7, 14, and 28 days according to effective legal and ethical protocols. The bone around the implants was severed 5 µm thick. After coloring with the Tricrom Goldner method, the sections that intercepted most centrally the intervention area were examined and photographed with an Olympus microscope. Results: The histologic result showed osseous healing within the healing chamber in the third to the endosteum of the implant after 7 days from the insertion. After 14 days, the osseous healing spread to 2/3 of the healing chamber. After 28 days, the whole healing chamber was occupied by bone. Conclusions: The healing chamber favored proper conditions for osseous healing, which began at the level of the endosteum. This statement is based on the histologic findings of bone formation after 7 days only in the third of the endosteum of the healing chamber. A 150 µm height of the healing chamber obtained in the rabbit cortical bone does not pose a risk of connective tissue proliferation. Full article

Background: Osseointegration is the main factor that ensures the long-term success of implant-prosthetic therapy, but besides this, there are other important factors, such as the quality of the alveolar bone and the time of placement of dental implants. The study aimed to analyze changes in the alveolar bone following tooth extraction, comparing natural healing with immediate implant placement, using fractal analysis on OPG images. Methods: This retrospective study included OPG images obtained before tooth extraction and 3 months after surgery in 91 patients who underwent maxillary and mandibular molar extractions and opted for either natural healing or immediate dental implant placement. Fractal analysis of OPG images was performed using Image J software, and the resulting measurements were subsequently statistically analyzed. Results: Most extractions were performed in the maxilla, and most were at the level of the first molar. The study group showed a faster healing process following immediate placement of dental implants, regardless of location, and a similar distribution of bone resorption and healing, with clear differences in location: the mandible had a faster healing process than the maxilla. Conclusions: Fractal analysis showed a better and quicker bone healing of the alveolar bone in immediate implant placement in molar areas compared with post-extraction natural healing, especially in the lower jaw. Full article

Tooth extraction induces changes in both hard and soft tissues, which may compromise implant placement. Leukocyte- and platelet-rich fibrin (L-PRF) is used to promote tissue healing, either alone or in combination with other grafting materials. Objective: This study aimed to compare post-extraction socket healing using L-PRF alone or combined with a biphasic calcium phosphate graft (HA/β-TCP) after eight weeks. Materials and Methods: 15 patients, both sexes, mean age 56.7 ± 8.2 years, requiring alveolar ridge preservation after single-rooted tooth extraction for subsequent implant placement, were included. Sockets were randomly assigned to four groups: control with blood clot only (CTR), autogenous bone graft (AB), L-PRF membrane (LPRF), and L-PRF combined with HA/β-TCP (LPRFHA). The protocol consisted of tooth extraction and immediate graft placement, followed by bone biopsy at 8 weeks for histomorphometric analysis and implant installation. New Bone Formation (NBF) was quantified from ten photomicrographs per sample using ImageJ software (version 1.54, 5 February 2025). One-way ANOVA with Bonferroni post hoc tests was applied, with statistical significance set at p ≤ 0.05. Results: A significant difference in NBF (%) was observed between the control and LPRFHA groups (p = 0.014), with greater bone formation in the control group (62.4 ± 18.6%) compared with LPRFHA (55.8 ± 17.2%; p = 0.012). No significant differences were found among AB, LPRF, and LPRFHA groups. LPRF and AB showed comparable bone formation (60.2 ± 17.5% and 60.1 ± 20.0%, respectively). Conclusions: L-PRF, either alone or combined with HA/β-TCP, can be used for alveolar ridge preservation in maxillary sockets. L-PRF, alone or with synthetic HA/β-TCP graft, effectively preserves the anterior maxillary ridge for early loading at eight weeks. All treatments achieved bone formation for implant placement, with the blood clot alone showing superior results. Full article