Flavia Queiroz Pirih

Periodontitis, a leading cause of tooth loss worldwide, arises from a dysregulated host immune response, and males consistently show higher prevalence and more severe disease than females. This disparity historically has been attributed to behavioral/environmental factors, but growing evidence indicates that biological sex, acting through hormonal signaling and sex chromosome–linked genetic mechanisms, independently shapes periodontal immune responses and subsequent bone resorption. In this review, we examine preclinical and clinical evidence on the impact of biological sex on host modulation therapies to prevent periodontitis. The IL-1β/inflammasome pathway and osteoclast differentiation via receptor activator of nuclear factor–κB ligand (RANKL)/osteoprotegerin (OPG) signaling both show clear sex-dependent regulation in experimental periodontitis, illustrating the biological complexity that single-target therapies must address in this heterogeneous condition. In a mouse model, inflammasome-mediated IL-1β signaling drives alveolar bone loss selectively in males, while females progress to comparable bone loss through IL-1β–independent mechanisms. IL-17 plays a dual role, driving inflammatory bone resorption while also supporting antimicrobial defense, and evidence points to this balance being sex dependent, with more severe effects observed in females when IL-17 signaling is disrupted. IL-6 is an established driver of periodontal bone loss, and although sex-specific data within periodontitis remain limited, sex-dependent anti–IL-6 receptor treatment responses have been observed in other inflammatory diseases that warrant further investigation. Complement-mediated immunity shows biological sex differences in humans and animal models, though whether these discrepancies directly influence periodontal disease progression needs to be determined. Resolvins and cyclooxygenase inhibitors also show sex-dependent effects outside the periodontal field. Collectively, this evidence positions biological sex as a tractable, currently underappreciated variable to improve host modulation strategies. Incorporating sex as a biological variable into preclinical and clinical periodontal research and ensuring sex-disaggregated data reporting offer a clear opportunity to develop precise, sex-informed nonsurgical therapeutics that better serve both male and female patients.

Background: The objectives of this Workshop were to evaluate the efficacy of scaffolding technologies for horizontal and vertical ridge augmentation; to evaluate the efficacy of substitute scaffolds for soft tissue augmentation in the context of implant therapy; to evaluate the efficacy of cells and/or biologics combined with scaffolds for alveolar bone regeneration; to evaluate the efficacy of cells and/or biologics combined with scaffolds for soft tissue regeneration in the context of implant therapy; and to evaluate emerging technologies and personalized strategies for improving hard and/or soft tissue defects around natural teeth and dental implants. Methods: The Workshop discussions were informed by five specifically commissioned systematic reviews from the following three Working Groups: Working Group 1 – Use of scaffolds for bone and soft tissue regeneration; Working Group 2 – Use of cells and/or biologics combined with scaffolds for hard and soft tissue regeneration; and Working Group 3 – Current, emerging, and personalized approaches for periodontal and peri‐implant tissue regeneration. The Workshop participants were informed by the compiled evidence from the five systematic reviews within each Working Group to address pertinent issues to inform clinical practice, research, and the public community. Results: The consensus among the Workshop group participants was that cellular therapies and biologics, alone and in combination with scaffolding technologies, offer strong potential in regenerating tissues around teeth and dental implants. There was variability in treatment outcomes depending on the overall evidence and the efficacy of these technologies, as well as on the specific defects and patient‐based constraints. The consensus report detailed the results and implications of the findings, demonstrating the value of these technologies in improving clinical and patient‐reported outcomes. Conclusions: Current regenerative approaches lead to long‐term stable outcomes at natural teeth as well as dental implant sites; novel technologies can benefit patients by enhancing longer‐term stability of teeth and implants to promote the health of the oral cavity and dentition; and artificial intelligence–enabled modeling can contribute to the identification of relevant features at the individual (as opposed to population) level, empowering patients to be active participants in their journeys and improving science‐to‐public communication.

Background: Peri‐implantitis is an inflammatory disease arising within a unique host–microbial–biomaterial ecosystem. Unlike periodontitis, peri‐implant tissues lack a periodontal ligament and epithelial junction integrity and interface with metal oxides on titanium surfaces. The inflammatory changes in peri‐implant disease not only affect the host but also extend to the implant surfaces, which undergo corrosion and particle release. These specific ecological features must be accurately captured in preclinical experimental models to provide mechanistic insight and enable translational success. Aim: This review evaluates preclinical and microengineered models of peri‐implantitis, focusing on how well they recapitulate the peri‐implant mucosal barrier, the biomaterial interface, and systemic modifiers. We propose minimum criteria for “true” peri‐implantitis models and outline ecosystem‐specific platforms for translational research. Materials and Methods: A literature search for this narrative review was conducted in PubMed, prioritizing in vivo peri‐implantitis models and their use in assessing systemic comorbidities (e.g., diabetes) and local risk factors on peri‐implant disease. Furthermore, emerging implant‐specific organ‐on‐a‐chip systems for 3D peri‐implant mucosa are reviewed. Results: Ligature‐ and infection‐based rodent and large‐animal models have elucidated key bacterial‐driven inflammatory pathways around dental implants, but careful consideration is needed to ensure long‐term chronicity and to account for titanium degradation as a costimulatory pathogenic factor. Comorbidity‐integrated models demonstrate that diabetes, vascular disease, and antiresorptive therapy amplify peri‐implant bone loss and can precipitate MRONJ‐like lesions. Organ‐on‐a‐chip peri‐implant mucosa platforms now enable controlled bacterial and titanium exposure, biomechanical strain, and human‐relevant barrier readouts, aligned with reduction principles and prioritizing Human‐Centered models. Clinical Relevance: Ecosystem‐specific models that incorporate microrough titanium, inflammatory biomaterial corrosion, barrier biology, and systemic risk factors are essential to advance the study of peri‐implantitis. Such models provide a strong foundation for implant‐specific investigations that move peri‐implantitis management beyond biofilm‐centric debridement into the management of host–microbial–biomaterial equilibrium.

Background: Traumatic dental injury (TDI) most often requires complex and interdisciplinary management. Several factors are associated with the success of TDI treatment, including proper treatment planning and periodontal maintenance. Methods: The present 16‐year follow‐up report describes the interdisciplinary management of an extrusive luxation of teeth #8 and #9 in a 9‐year‐old‐patient. Results: After the extrusion, endodontic treatment was performed on teeth #8 and #9 and then periodontal treatment with supra and subgingival debridement associated with locally antibiotic application was done. Once periodontal treatment was stable, orthodontic treatment started. During orthodontic treatment, the patient was advised to have periodontal maintenance every 3–4 months. At the 16‐year follow‐up appointment, both teeth were in function and in acceptable esthetic condition. Conclusion: This report demonstrates that proper diagnosis combined with interdisciplinary therapeutic approaches and periodontal maintenance could lead to long‐term successful and stable outcomes. Key points: The effective management and proper treatment of dental trauma depend on an accurate diagnosis. Interdisciplinary management is essential for successful treatment of dental trauma. Patient adherence to periodontal maintenance directly influences outcomes. Plain language summary: When dental injuries are diagnosed correctly and treated with the help of different dental specialists—along with regular periodontal care—the long‐term results can be stable and successful.

This study is aimed at characterizing the physicochemical and biological properties of a hydroxyapatite–silver (HAp‐Ag) composite for bone regeneration. HAp and HAp‐Ag powders were analyzed using field emission scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, X‐ray diffraction and fluorescence, and Fourier transform infrared spectroscopy. Cylindrical pellets obtained by powder pressing and sintering were evaluated for fracture toughness, compressive strength, relative density, porosity, and wettability. Cell viability was assessed using the Alamar Blue assay. In the in vivo experiment, an 8‐mm critical‐size calvarial defect was surgically created in 36 male Wistar rats randomly divided into three groups: control group (CG), untreated defect; HAp group, defect filled with HAp pellet; and HAp‐Ag group, defect filled with HAp‐Ag pellet. Euthanasia was performed after 90 days, and calvaria samples were analyzed by μ ‐CT, histology, cytokine quantification, and gene expression analysis. The powders showed an irregular, agglomerated morphology, with HAp elements and silver detected in the HAp‐Ag sample. Incorporation of Ag into HAp increased fracture toughness (0.66–0.94 MPa.m ^1/2 ) and porosity (16.43%–25.95%) and reduced compressive strength (43.17–23.99 MPa) and contact angle (36.32°–10.51°). MC3T3‐E1 preosteoblastic cell viability was higher on HAp‐Ag surface compared to HAp pellets at Days 1 and 7. Compared to CG, defects filled with biomaterials showed greater bone formation and better bone quality parameters. In addition, a more advanced stage of bone maturation was observed in the animals treated with HAp‐Ag. HAp‐Ag composite upregulated TNF‐ α and IL‐1 β levels and Procollagen 3 and eNOS gene expression compared to CG. Silver incorporation into HAp increased fracture toughness and porosity, reduced compressive strength, and improved wettability. Despite these changes, HAp‐Ag enhanced cell viability and in vivo bone maturation, indicating that Ag addition does not compromise and may improve its bone regeneration potential.

Background: Bisphosphonates (BPs) are effective in managing bone diseases due to their anti‐resorptive properties but are linked to medication‐related osteonecrosis of the jaw (MRONJ), particularly concerning dental implants. This study explored the combined impact of ligature‐induced peri‐implant inflammation and zoledronic acid (ZA), a BP, using a murine model.Methods: Twenty‐four mice underwent bilateral maxillary molar extractions and implant placements, with ZA or vehicle treatment and ligature placement on the left side. Two groups were defined: group 1 (vehicle‐treated) with control (Veh‐C) and ligature (Veh‐L) implants, and group 2 (ZA‐treated) with control (ZA‐C) and ligature (ZA‐L) implants. Clinical, micro‐CT, histological, and immunohistochemical analyses were performed. We hypothesized that peri‐implant inflammation elevates MRONJ risk with BP treatment.Results: Ligature groups showed increased soft tissue edema compared to controls, without differences between vehicle and ZA treatments. The Veh‐L group exhibited significantly greater bone loss than other groups. Histology showed higher inflammatory infiltrate in ligature groups. Osteocyte empty lacunae and osteonecrosis were significantly greater in ZA‐L. Picrosirius red staining revealed disorganized collagen fibers and separation in ZA‐L. Immunohistochemistry showed increased neutrophils (NIMP‐R14+) and monocytes/macrophages (CD11b+) in the ligature groups, with no significant differences between Veh‐C and ZA‐C.Conclusion: Ligature treatment enhances peri‐implant inflammation, with ZA heightening the risk of MRONJ. These findings highlight the critical importance of early detection and management of peri‐implant inflammation in patients undergoing BP therapy, particularly those at high risk of MRONJ. Clinicians should emphasize preventive measures, such as regular monitoring of peri‐implant health and reducing local inflammatory triggers, to mitigate the adverse effects of BPs on peri‐implant bone health.Plain Language Summary: Dental implants are a reliable solution to replace missing teeth. However, like natural teeth, implants can develop inflammation around them—peri‐implantitis. Our study found that, when this inflammation occurs in patients taking BPs (a medication commonly used to treat osteoporosis and other bone diseases), the risk of developing a serious jaw condition called osteonecrosis (ONJ) increases significantly. ONJ prevents the jawbone from healing properly, leading to pain, infection, and even exposed bone. These findings highlight the importance of preventing and managing inflammation around dental implants to reduce the risk of complications, especially in patients taking BPs. Our research suggests regular dental check‐ups and proper oral hygiene can help maintain implant health and prevent severe bone‐related conditions. Patients and healthcare providers can take proactive steps to improve long‐term oral health outcomes by understanding these risks.