Search Results (418)

Dental implants are a popular clinical procedure for the rehabilitation of fully and partially ede ntulous patients. There is long-term evidence that implant-supported dental prostheses represent a predictable treatment for replacing missing teeth. However, several types of complications may arise, which can compromise implant treatment outcome. Peri-implant disease is a growing biological complication, consisting of a progressive loss of supporting bone, associated with microbial biofilm and clinical inflammation. It represents a concern for clinicians and patients, having a negative impact on quality of life. This narrative review aimed at summarize the current knowledge on etiology, epidemiology, risk factors, and pathogenesis of peri-implant disease. It also focused on the diagnostic potential of active matrix metalloproteinase-8 (aMMP-8) in peri-implant sulcular fluid for assessing the status of peri-implant tissues and the risk of developing peri-implantitis. A literature search was conducted in PubMed and Scopus databases using search terms like: peri-implantitis, peri-implant biomarkers, aMMP-8, implant maintenance, risk assessment. Clinical studies, systematic reviews, meta-analysis and consensus papers published up to June 2025 were considered. Finally, based on the main factors involved in the onset and progression of peri-implant disease, a new protocol was conceived for determining the optimal implant maintenance scheduling for individual patients. The Biomarker-Guided Implant Maintenance (BGIM) protocol considers a few key parameters, among which aMMP-8 level, and proposes three categories associated with different levels of risk for peri-implantitis. The higher the risk, the more frequently a patient should undergo professional maintenance, to prevent peri-implant disease, with potential favorable effects on implant longevity. The proposed BGIM protocol, that requires prospective validation, represents a structured and clinically applicable biomarker-driven framework for individualizing implant maintenance scheduling by integrating real-time chairside quantification of aMMP-8 with established patient-related risk factors. Full article

Three-dimensional (3D) bioprinting has rapidly emerged as a transformative technology at the interface of biomedical engineering and regenerative medicine. By enabling the spatially controlled deposition of living cells, biomaterials, and bioactive molecules, it offers an unprecedented potential to fabricate functional tissues and potentially whole organs in the future. This review explores recent advances in bioprinting materials, processes, and applications, emphasizing the integration of bioinks, printing methods, and mechanical design principles that underpin tissue functionality. Natural and synthetic biomaterials such as hydrogels (e.g., collagen, alginate), polyethylene glycol (PEG), and polyesters like PLGA are evaluated in terms of biocompatibility, printability, and degradation behavior. Key bioprinting modalities, including extrusion, inkjet, and laser-assisted bioprinting, are compared based on printing resolution, cell viability, and scalability. Structural considerations such as scaffold architecture, mechanical stability, and biomimetic design are discussed in relation to native tissue mechanics and requirements. The review also surveys emerging applications in tissue engineering (e.g., bone, cartilage, skin replacements), organ-on-a-chip systems for drug testing, and patient-specific implants, while addressing persistent challenges such as standardization of biofabrication, regulatory and ethical considerations, and manufacturing scale-up. Finally, future trends, including the integration of artificial intelligence (AI) and robotic automation, multi-material and four-dimensional (4D) bioprinting, and the maturation of personalized bioprinting strategies, are highlighted as pathways toward more autonomous and clinically relevant bioprinting systems. Collectively, these developments signify a paradigm shift in how biological constructs are designed and manufactured, bridging the gap between laboratory research and clinical translation. Full article

Small extracellular vesicles (sEVs; commonly referred to as “exosomes” in many studies) are nanoscopic messengers released by healthy and diseased cells that mediate intercellular communication by transferring proteins, lipids, and nucleic acids to local or distant recipient cells. In this narrative review, we synthesize recent evidence linking tissue-derived sEVs to neurological disorders (including neurodegeneration and traumatic brain injury), metabolic syndrome, cardiovascular diseases, cancers, and bone diseases, with a particular emphasis on CNS–periphery crosstalk across the blood–brain barrier. Compared with prior reviews that focus on single organ systems, we highlight cross-disease, cross-tissue mechanisms and summarize candidate biomarker cargos and therapeutic strategies in dedicated tables. While accumulating data support brain–body communication via sEVs, the concept of CNS-derived sEVs acting as a “third central efferent pathway” is presented here as an emerging hypothesis that complements—rather than replaces—neuronal and endocrine signaling. Overall, tissue-derived sEVs represent a promising but still evolving platform for diagnostic and therapeutic innovation, warranting standardized isolation/characterization and further clinical validation. Full article

In this research, Fe-P scaffolds were successfully fabricated by the powder metallurgy method for the first time, using NaCl as the space holder for bone tissue engineering applications, with apparent porosities of approximately 70%. The Fe₃P powder was successfully synthesized by the mechanochemical method under an argon atmosphere using an initial mixture of Fe and P powders. The XRD patterns show that Fe₃P was obtained after sintering the milled powders at 1000 °C. Fe, Fe₃P, and Fe-50 wt% Fe₃P composite scaffolds and bulk pellets were prepared by sintering the milled powder at 1000 °C. Furthermore, the mechanical properties (compression strength) and bioactivity of the Fe-P scaffolds were determined. According to the compression test results, the composite scaffold showed higher compressive strength, lower fracture strain, and higher elastic modulus than the Fe and Fe₃P scaffolds, indicating that adding Fe₃P to Fe improves the mechanical properties. Moreover, among the scaffolds prepared by sintering at 1000 °C, the Fe scaffold exhibited the highest corrosion rate compared to the Fe₃P and composite samples, while the corrosion resistance of the composite sample was 3 times higher than that of the Fe sample. The ICP analysis showed that the amount of Fe released from the bulk pellets during soaking in PBS solution after four weeks was 3220 μg/dL, 4003 μg/dL, and 4774 μg/dL for the composite, Fe₃P, and Fe samples, respectively. The composite sample showed the highest cell viability, while the Fe sample had the lowest. The compressive strength (12.62 MPa) and fracture strain (5.98%) of the porous sintered composite scaffold at 1000 °C were within the range of trabecular bone, while the compressive strength of the composite sample was 17 times higher than that of the Fe sample. Furthermore, the MTS test showed that all the samples had good viability, while the composite sample had the best cell viability. The scaffolds were not cytotoxic. It can be concluded that the mechanical and biological properties of the composite sample were superior to those of the Fe and Fe₃P samples and that it may be a promising candidate for bone tissue engineering applications, especially for trabecular bone replacement. Full article

Impaired bone healing is a major challenge in orthopedic and trauma surgery, often causing long-term disability and high costs. While autologous bone grafting is the gold standard, it is limited by donor site morbidity, low availability, and surgical risks. As an alternative, surgical site-released tissue (SSRT) collected intraoperatively offers a readily available source of regenerative cells and bioactive factors. This study investigates the potential of SSRT-derived mesenchymal stromal cell (MSC)-like cells and their extracellular vesicles (EVs) to support bone healing in a cell-free approach. SSRT samples from 30 patients undergoing elective hip replacement were collected using a surgical vacuum filter. MSC-like cells were isolated and characterized based on International Society for Cellular Therapy (ISCT) criteria. Interestingly, many SSRT-derived MSC-like cells expressed CD34, a marker typically absent in cultured MSCs but linked to tissue-resident stromal cells, suggesting distinct regenerative properties. These cells also showed slow proliferation rates (P1: 8.7 ± 3.2 days; P2: 8.2 ± 5.4 days). EVs were isolated from osteogenically stimulated (EVs^MSC/O+) and unstimulated (EVs^MSC/O−) MSCs over three weeks. Antibody profiling revealed distinct cargo compositions, with a notable enrichment of CD13+ EVs in the stimulated group. Further in vivo and functional studies are needed to clarify underlying mechanisms and confirm therapeutic efficacy. Full article

Background: Autogenous tooth-derived grafts have been proposed as an alternative to xenografts for alveolar ridge preservation, offering biological similarity to bone and potentially more favorable remodeling. This study compared the healing outcomes of a collagenated xenograft, and a tooth-derived graft prepared with an automated processing device. Methods: Six Beagle dogs underwent bilateral extraction of the third and fourth mandibular premolars. Each animal contributed two sockets grafted with root-derived particulate prepared using an automated device for tooth cleaning, grinding, and demineralization, and two sockets grafted with a collagenated xenograft, all covered by a collagen membrane. After 3 months, histological sections were analyzed to assess crestal dimensions and the relative proportions of mature (lamellar) and immature bone (woven/parallel fibered), residual graft material, and soft tissues. Results: Lingual crest height did not differ between groups, whereas the buccal crest was slightly higher at xenograft sites compared with the tooth-graft sites. The tooth-graft group exhibited significantly fewer residual particles (0.5 ± 1.1%) and a higher proportion of total bone (65.6 ± 9.1%) compared with the xenograft group, which showed 19.7 ± 16.0% graft remnants (p = 0.032). Corticalization at the socket entrance was observed predominantly in the tooth-graft sites. No inflammatory infiltrates were detected in the examined section. Conclusions: Tooth-derived grafts promoted an almost complete replacement by vital bone with minimal residual material, whereas xenografts provided slightly better buccal contour preservation but resulted in regenerated tissues containing persistent graft particles. The biological differences observed may have implications for subsequent implant placement. Full article

Osteoporosis (OP) is a common chronic disease that significantly increases the risk of bone fractures. Pharmacotherapy uses, among others, 17beta-estradiol (E2), which has been replaced in recent years by raloxifene hydrochloride (RLX). The need for long-term, high-dose therapy with these drugs is associated with serious adverse effects. The aim of this review is to analyze the current state of knowledge over the last 5 years (2020–2025) regarding the use of nanoparticles (NPs) in the delivery of E2 and RLX, with particular emphasis on their impact on bioavailability, pharmacokinetic profile, reduction in adverse effects, and improvement in the effectiveness of postmenopausal osteoporosis therapy. Preclinical studies show that combining E2 or RLX with various types of NPs reduces cytotoxicity, improves pharmacokinetic parameters, and enhances the therapeutic effects of drugs used in postmenopausal osteoporosis. These effects are mainly attributed to improved pharmacokinetics and controlled drug release, rather than confirmed active tissue targeting. However, these findings are based on preclinical models and require further validation in clinical studies. The analysis concludes that while NP systems significantly enhance the pharmacokinetic profile and safety of E2 and RLX in preclinical models, claims of true bone-specific targeting remain largely unsubstantiated, highlighting a key area for future research. Full article

Owing to their high strength characteristics, chemical stability, and piezoelectric activity, vinylidene fluoride (VDF) copolymers have become promising materials for creating implants to replace bone tissue defects. However, a significant drawback of these materials is the biological inertness of their surface, which leads to unsatisfactory integration with the patient’s bone tissue. In this study, we propose a single-step approach for immobilizing hydroxyapatite (HAp) on the surface of porous implants made of vinylidene fluoride and tetrafluoroethylene copolymer (P(VDF-TeFE)). This method consists of treating the surface of the product with a mixture of solvents while simultaneously capturing HAp microparticles. Using scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS), it was shown that the proposed method preserves the morphology of model implants (pore diameter and printed line thickness) and allows HAp to cover up to 63 ± 14% of their surface, reaching concentrations of calcium and phosphorus up to 6.0 ± 1.3 and 3.6 ± 0.7 at. %, respectively, imparting superhydrophilic properties to them. Optical profilometry revealed that the surface roughness of samples increased by more than seven times as a result of HAp immobilization. X-ray diffraction analysis (XRD) confirmed that the piezoelectric phase of P(VDF-TeFE) is preserved after treatment, as are the compressive strength characteristics of the samples. Hydroxyapatite immobilization significantly improved the adhesion and osteogenic differentiation of multipotent stem cells cultured with P(VDF-TeFE)-based samples. Thus, the proposed method can significantly enhance the biological activity of implants based on the piezoelectric VDF copolymer. Full article

Background: The global increase in orthopedic implant use—both for trauma fixation and arthroplasty—has profoundly transformed musculoskeletal surgery. As a consequence, fractures occurring in the presence of implants have become more frequent and clinically relevant. Yet, these injuries are currently described using highly heterogeneous terminology, including periprosthetic (fracture occurring in the presence of a prosthetic joint replacement) peri-implant (fracture occurring around an osteosynthesis or fixation device), implant-related, and hardware-related fractures (umbrella terms encompassing both prosthetic and fixation devices, used descriptively rather than classificatorily). This coexistence of multiple, context-specific terminologies hinders clinical communication, complicates registry documentation, and limits research comparability across orthopedic subspecialties. Because fractures occurring in the presence of orthopedic implants significantly alter load transfer, muscle force distribution, and musculoskeletal biomechanics, a clear and unified terminology is also relevant for muscle-focused research addressing implant–tissue interaction and functional recovery. Objective: This systematic review aimed to critically analyze the terminology used to describe fractures influenced by orthopedic implants, quantify the heterogeneity of current usage across anatomical regions and publication periods, and explore the rationale for adopting a unified umbrella term—“artificial fracture.” Methods: A systematic search was performed in PubMed, Scopus, and Web of Science from January 2000 to December 2024, following PRISMA guidelines. Eligible studies included clinical investigations, reviews, registry analyses, and consensus statements explicitly employing or discussing terminology related to implant-associated fractures. Data were extracted on publication characteristics, anatomical site, terminology employed, and classification systems used. Quantitative bibliometric and qualitative thematic analyses were conducted to assess frequency patterns and conceptual trends. Results: Of 1142 records identified, 184 studies met the inclusion criteria. The most frequent descriptor in the literature was periprosthetic fracture (68%), reflecting its predominance in arthroplasty-focused studies, whereas broader and more practical terms such as implant-related and peri-implant fracture were more commonly used in musculoskeletal and fixation-related research. Terminological preferences varied according to anatomical site and implant type, and no universally accepted, cross-anatomical terminology was identified despite multiple consensus efforts. Discussion and Conclusions: The findings highlight persistent heterogeneity in terminology describing fractures influenced by orthopedic implants. A transversal, descriptive framework may facilitate communication across subspecialties and support registry-level harmonization. Beyond orthopedic traumatology, this approach may also benefit muscle and musculoskeletal research by enabling more consistent interpretation of data related to muscle–bone–implant interactions, rehabilitation strategies, and biomechanical adaptation. Full article

Background and Objectives: Reduced bone quality due to osteoporosis significantly complicates oral rehabilitation and bone regeneration therapies. While Vitamin D (Vit. D3) is crucial for osteogenesis, systemic administration often lacks local efficacy. This study aimed to evaluate the osteoregenerative potential of a novel Chitosan-based nanostructured scaffold (NS) loaded with Vit. D3, underlining its efficacy in vitro and in an ovariectomized (OVX) rat model of osteoporosis. Materials and Methods: Chitosan NSs were fabricated with varying Vit. D3 concentrations. In vitro assessments included cytotoxicity (MTT assay), cell viability (Alamar Blue), and mineralization (Alizarin Red) using human dental follicle stem cells. In vivo, 30 Wistar rats were ovariectomized to induce osteoporosis (confirmed by biomarkers Osteocalcin and β-CTX) and were divided into three groups (n = 10). Bilateral maxillary bone defects were treated with (1) a Control (clot only), (2) a Hemostatic Sponge with Vit. D3 (HS/Vit. D3), or (3) an NS loaded with Vit. D3 (NS/Vit. D3-6.25 ng/mL). Histological and morphometric analyses were performed at 4 and 8 weeks. Results: In vitro, the NS loaded with 6.25 ng/mL Vit. D3 demonstrated superior cytocompatibility, achieving a cell viability of 117.77% at 72 h and significantly enhanced calcium nodule deposition compared to controls. In vivo, a total of 44 defect sites were analyzed following the exclusion of compromised samples (Control: 16 sites; HS/Vit. D3: 16 sites; NS/Vit. D3: 12 sites). The NS/Vit. D3-6.25 ng/mL group exhibited the highest degree of mature bone formation and vascularization (p < 0.05) compared to the Control and HS/Vit. D3 groups. While cellular activity (osteoblasts/osteocytes) was initially higher in the HS/Vit. D3 group, the NS/Vit. D3-6.25 ng/mL group achieved superior structural integration and scaffold replacement by mature bone tissue over time. Conclusions: The novel Vit. D3-loaded Chitosan NS effectively promotes bone regeneration in osteoporotic conditions. It supports osteogenic differentiation in vitro and enhances bone matrix maturation in vivo, suggesting its potential as a bioactive scaffold for regenerative dentistry. Full article

Microgravity (µg)-generated three-dimensional (3D) multicellular aggregates can serve as models of tissue and disease development. They are relevant in the fields of cancer and in vitro metastasis or regenerative medicine (tissue engineering). Driven by the 3R concept—replacement, reduction, and refinement of animal testing—µg-exposure of human cells represents a new alternative method that avoids animal experiments entirely. New Approach Methodologies (NAMs) are used in biomedical research, pharmacology, toxicology, cancer research, radiotherapy, and translational regenerative medicine. Various types of human cells grow as 3D spheroids or organoids when exposed to µg-conditions provided by µg simulating instruments on Earth. Examples for such µg-simulators are the Rotating Wall Vessel, the Random Positioning Machine, and the 2D or 3D clinostat. This review summarizes the most recent literature focusing on µg-engineered tissues. We are discussing all reports examining different tumor cell types from breast, lung, thyroid, prostate, and gastrointestinal cancers. Moreover, we are focusing on µg-generated spheroids and organoids derived from healthy cells like chondrocytes, stem cells, bone cells, endothelial cells, and cardiovascular cells. The obtained data from NAMs and µg-experiments clearly imply that they can support translational medicine on Earth. Full article

Bone is a structurally complex and dynamic tissue that plays a crucial role in mobility and skeletal stability. However, conditions such as osteoporosis, osteoarthritis, trauma-induced fractures, infections, and malignancies often necessitate the use of orthopedic and dental implants. Despite significant progress in implant biomaterials, challenges such as bacterial infection, inflammation, and loosening continue to compromise implant longevity, frequently leading to revision surgeries and extended recovery times. Smart coatings have emerged as a next-generation solution to these problems by providing on-demand, localized therapeutic responses to microenvironmental changes around implants and promoting bone regeneration. Such coatings can minimize antibiotic resistance by enabling controlled, stimulus-triggered drug release. Although the idea of using pH-sensitivity as a tool to make smart coatings is not a new thought, there are no options currently good enough to enter clinical studies. This review provides a comprehensive overview of recent advances in pH-sensitive polymers, hybrid composites, porous architectures, and bioactive linkers designed to dynamically respond to pathological pH variations at implant sites. By investigating the mechanisms of action, antibacterial and anti-inflammatory effects, and roles in bone regeneration, it is shown that the ability to provide time-dependent drug release for both short-term and long-term infections, as well as keeping the environment welcoming to the bone cell growth and replacement, is not an easy goal to reach, even with a fully biocompatable, non-toxic, and semi-biodegradable (one that releases the drug, but does not fade away) coating material compound. Reviewing all available options, including their functions and failures, finally, emerging trends, translational barriers, and future opportunities for clinical implementation are highlighted, underscoring the transformative potential of bioresponsive coatings in orthopedic and dental implant technologies. Full article

Cervicofacial actinomycosis is a well-recognized infectious disease caused by Actinomyces, a Gram-positive filamentous bacterium. In contrast, Nocardia, a morphologically similar, hyphae-forming organism, is an exceedingly rare cause of cervicofacial abscesses, and even more uncommon associated osteomyelitis of mandible. We present such a case involving a kidney transplant recipient who presented with opioid-induced constipation, along with left jaw pain and swelling. CT scan of the soft tissue in the neck revealed a complex cervicofacial abscess with enhancement of underlying mandible. Culture growth and RNA sequencing of USG-guided aspirate identified a Nocardia species closely related to N. beijingensis/exalbida. The patient initially received broad-spectrum antibiotics, including ceftriaxone, imipenem, and trimethoprim-sulfamethoxazole (TMP-SMX). Imipenem was later discontinued in view of new-onset unexplained encephalopathy and replaced with linezolid, which was subsequently switched to minocycline following thrombocytopenia development. Minocycline therapy was intended for a total of 12 months. TMP-SMX was avoided long-term due to avoid nephrotoxicity risk in kidney transplant patients. On six-month follow-up, the patient showed clinical and radiological improvement; minocycline was discontinued after additional six months. This case highlights the importance of considering Nocardia as a differential diagnosis in immunosuppressed patients presenting with cervicofacial symptoms, especially following orofacial surgery or trauma. Early recognition, prompt diagnosis, and appropriate antibiotic therapy with adequate bone penetration seem crucial for optimal management and may help avoid the need for surgical intervention. Full article

Background/Objectives: Conventional radiographic methods, although considered the gold standard for dental implantology, are not exempt from certain limitations, including their two-dimensional nature, the exposure to ionizing radiation and the inability to assess soft tissues. Ultrasonography (US) has recently emerged as a promising diagnostic tool due to its non-invasive and radiation-free properties. This systematic review aimed to evaluate the clinical applications of ultrasonography in implant dentistry, focusing on both preoperative planning and postoperative monitoring and to compare its diagnostic performance with conventional imaging modalities. Methods: A comprehensive search was performed in PubMed, Scopus, Web of Science, and Cochrane databases (2005–2025) to identify clinical studies evaluating the diagnostic applications of ultrasonography in implant dentistry. The review included randomized controlled trials, diagnostic accuracy studies, case series and case reports. Risk of bias was assessed using the RoB-2 tool for RCTs, QUADAS-2 for diagnostic studies and the JBI checklist for case reports and series. Results: 17 eligible studies were included in this review, comprising 4 RCTs, 10 diagnostic accuracy studies, 2 case report and 1 case series, for a total of 371 patients evaluated. Ultrasonography proved effective in the preoperative setting for evaluating mucosal thickness, keratinized mucosa, tissue phenotype, ridge width and bone morphology, often showing high agreement with CBCT and clinical measurements. In the postoperative phase, US enabled monitoring of soft tissue healing, vascular perfusion, graft maturation and detection of peri-implant pathology, with some studies showing correlations between early ultrasonographic findings and long-term clinical outcomes. Comparative studies revealed strong concordance with CBCT (mean deviations < 0.5–1 mm) and superior performance in both soft tissue visualization and cases affected by radiographic artifacts. Conclusions: Ultrasonography represents a promising adjunctive tool in implant dentistry, capable of complementing or, in selected scenarios, replacing conventional radiographic methods. While current evidence highlights its diagnostic potential across different stages of implant therapy, further standardized, large-scale clinical studies are required before routine integration into daily practice. Full article